B^OIOOY 


USWW^ 


GENERAL 

PATHOLOGY 


BY 

DR.    ERNST   ZIEGLER 

PROFESSOR  OF   PATHOLOGICAL    ANATOMY    AND  OK   GENERAL    PATHOLOGY 
IN   THE    UNIVERSITY    OF    FREIBURG    IN    BKEISGAU 


TRANSLATED  FROM 
THE   ELEVENTH    REVISED   GERMAN    EDITION 

(gUSTAV   FISCHER,    JENA,    1905) 


EDITED   AND  BROUGHT   UP  TO   DATE 


ALDRED  SCOTT   WARTHIN,  Ph.D.,  M.D. 

PROFESSOR  OF    PATHOLOGY    AND   DIRECTOR   OF  THE   PATHOLOGICAL  LABORATORY    IN   THE 
UNIVERSITY    OF   MICHIGAN,    ANN   ARBOR,    MICHIGAN 


WITH    604   ILLUSTRATIONS    IN    BLACK   AND    IN    COLORS 


NEW    YORK 

WILLIAM    WOOD    AND   COMPANY 

MDCCCCXVIII 


\ 


6 


JOPYKIGHT,   1908, 

Bt   WIL1.IAM  WOOD  AND  COMPANY. 


AUTHOR'S  PltEFACK  TO  THE   KLE\  ENTII   EDITION. 


Ix  the  prepanitiou  of  this  newetlition  1  Jiave  cMjdea\ died  lo  utili/c  as 
fully  as  possible  the  i-eseaivhes  of  the  last  several  years,  and,  in  so  far  as 
these  have  given  us  new  facts  and  represent  actual  advances  in  our  knowl- 
edge of  ]>athological  processes,  to  incorporate  them  into  the  contents  of 
the  hook.  It  has  become  almost  impossible  to  review  tlie  great  mass  of 
literatni-e  concerning  the  i^athogenic  micro-organisms,  their  life  history, 
and  their  effects  upon  the  human  organism;  l)ut  E  hope  that  the  essential 
and  established  results  of  recent  in\  estigations  have  not  escaped  me,  and 
that  I  have  estimated  them  at  their  i)roper  worth.  1  may  mention  with 
especial  emphasis  the  reseaiches  of  vSchaudinn  on  the  si)irocha*tte  and  the 
parasites  of  malaria;  also  those  of  other  authors  on  the  trypanosomata, 
various  pathogenic  bacteria,  the  agglutinins,  ijrecipitins,  cytolysius,  and 
hiBmolysins,  as  well  as  the  numerous  investigations  and  theoretic  observa- 
tions that,  based  upou  Ehrlieh's  side-chain  theory,  have  been  canied  out 
concerning  the  toxic  action  of  bacterial  products  and  the  formation  of 
antitoxic  and  antibacterial  substances. 

During  recent  years  an  immense  amount  of  literature  concerning 
t  uberculosis  has  appeared;  but  our  previous  views  conceining  its  etiology 
and  genesis  have  not  been  materially  alteivd.  Koclf  s  \  iew  as  to  the 
ditference  between  human  and  bovine  tuberculosis  is  a])plicable  only  in 
so  far  as  certain  ditierences  in  the  characteristics  of  tiie  two  strains  of 
bacilli  are  concerued.  For  all  these  differences  it  is  true  that  bo\  ine 
tubercidosis  is  communicable  to  man,  and  the  domestic  aninmls  may  be- 
come infected  from  tuberculous  human  beings.  Yon  liehring's  publica- 
tion that  infants  may  be  easily  infected  through  milk  containing  tubercle 
bacilli  has  only  confirmed  well-known  views.  The  attempt  of  von  IJehring 
to  re fei- all  cases  of  tuberculosis  to  an  intestinal  infection  occurring  in 
infancy  is  doubtless  an  eiior,  and  is  not  likely  to  d«'sti'oy  tlie  belief 
that  tuberculosis  is  most  frequently  an  air-borne  infection  and  enters 
primarily  through  the  lungs. 

The  researches  concerning  the  etiology,  genesis,  and  mo]i)hology  of 
neoplasms  have  likewise  been  numerous  and  extensive ;  nevertheless,  any 
expectations  of  a  great  advance  in  our  knowledge  of  the  etiology  of  neo- 
plasms are  doomed  to  disappointment.  Tlie  attempts  to  establish  a  para- 
sitic etiology  for  tumoi-s  have  entirely  failed,  and  the  extensive  statistics 
that  have  l)een  amassed  concerning  the  distribution  of  carcinoma  liave 


IV  AUTHOR  S    PREFACE    TO    THE    ELEVENTH    EUITIOX. 

led  to  results  that  cuu  be  regarded  only  as  aiitagouistic  to  the  parasitic 
theorj-.  Of  greater  value  have  been  the  researches  on  the  histogeuesis  of 
tumors ;  yet  i  find  in  these  essentially  onlj^  a  confirmation  and  a  more  thor- 
ough grounding  of  our  older  views.  I  cannot  bring  myself  to  the  accept- 
ance of  all  the  latest  views,for  example,  the  assimiption  that  the  prelimi- 
nary condition  of  tumor  development  is  to  be  found  in  the  isolation, 
disconnection,  and  misplacement  of  germinal  anlage  or  of  single  cells 
during  embryonal  or  extrauterine  life  (Ribbert,  Borrmann),  or  that  the 
epithelial  cells  of  a  carcinoma  can  become  transformed  into  connective- 
tissue  cells  (Krompecher). 

Significant  advances  in  the  theory  of  fatty  degeneration  and  glycogen 
deposit  are  also  to  be  noted ;  and  although  many  problems  must  still  wait 
a  solution,  our  knowledge  concerning  these  processes  has  been  greatly 
furthered  through  the  labors  of  recent  years. 

The  long  discussion  over  the  significance  of  the  cells  appearing  in  the 
tissues  during  the  course  of  inflanmnition  has  at  last  reached  certain 
conclusions.     The  questions  still  unsettled  are  of  minor  importance. 

The  arrangement  of  the  book  is  left,  on  the  whole,  as  in  the  last  edition ; 
but  I  have  not  simj)ly  inserted  the  new  facts  and  views,  many  sections 
having  been  entirely  recast  to  agree  with  the  additions.  The  number 
of  illustrations  has  been  increased  from  586  to  604.  The  bibliography 
has  been  given  a  careful  iwision  and  ])ronght  up  to  the  autumn  of  this 
year. 

E.    ZlKGLER. 
Fkeibi:i!<;  im  Buki^gai,  December,  190-t. 


EDITOR'S  PREFACE. 


In  the  traiislatiou  of  tlie  last  (elevouth)  edition  of  Ziegler's  ^^Geueral 
Pathology  "  the  editor  has  eudeavored  to  cany  out  the  same  plan  followed 
in  the  preparation  of  the  tenth  edition,  viz.,  to  give  a  simple  and  con- 
sistent English  rendering  of  the  text  and  spirit  of  the  original,  suitable 
to  the  needs  of  the  medical  student.  The  original  matter  has  been  given 
without  change  or  omission.  So  rapid,  however,  has  been  the  progress 
of  pathological  knowledge  that,  in  the  three  years  elapsing  since  the 
book  left  Ziegler's  hands,  luimerous  important  facts  luiva  been  estab- 
lished and  new  theories  advanced.  In  order,  therefore,  to  bring  the 
work  up  to  the  present  date,  the  results  of  recent  investigations,  in  so 
far  as  they  have  pro\'ed  to  be  of  value  or  of  interest,  have  been  inserted 
into  the  book  in  the  form  of  additions  to  the  paragraphs  in  fine  print. 
Such  interlardments  include  recent  observations  on  the  effects  of  Roentgen 
irradiation,  heredity,  phagocytosis,  opsonins,  blood-plates,  thrombosis, 
necrosis,  cloudy  swelling,  fatty  degeneration,  calcification,  regeneration, 
inflammation,  malignant  neoplasms,  tuberculosis,  syphilis,  relapsing 
fever,  spirochiTetie,  protozoa,  etc.  In  subject-matter  the  work  has  thus 
been  brought  up  to  the  date  of  issue.  The  bibliography  has  also  been 
revised,  and  the  most  important  contributions  of  the  last  three  years  in- 
cluded. Through  these  changes  and  additions  the  editor  liopes  and  be- 
lieves that  the  present  edition  will  become  an  adequate  English  reiiie- 
sentative  of  the  original  German  work. 

It  seems  fitting  here  to  pay  an  American  tribute  to  tlie  memory  of 
the  author,  Geheimer  Hofrat  Ernst  Ziegler,  Professor  in  the  University 
of  Freiburg,  who  died  on  the  30th  of  November,  1905,  in  the  fifty-seventh 
year  of  his  age.  His  fame  rests  upon  liis  text -book  ratlier  than  upon  his 
investigations,  although  these  included  a  number  of  ini])ortant  contribu- 
tions. Passing  through  eleven  editions,  tianslated  iulo  English,  French, 
and  Italian,  the  "  Ziegler  "  became  a  familiar  and  final  authority  wherever 
the  study  of  patliology  was  prosecuted.  Devoting  his  life  to  the  per- 
fecting of  the  work,  constantly  improving  it  in  material  and  illustrations, 
the  author  made  of  it  a  splendid  example  of  a  scientific  text-book  prac- 
tically free  from  subjectivity,  oue-sidedness,  and  prejudice.  To  this  one 
achievement  alone  the  students  of  medicine  during  the  last  twenty-five 
years  owe  a  large  part  of  their  medical  culture,  and  in  this  respect  its 
influence  upon  the  recent  developmeut  of  medicine  can  hardly  l)e  esti- 


VI  EDITOR  S    PREFACE. 

mated.  Witliiii  late  years  there  has  been  fostered  somewhat  a  tendency 
toward  the  dis])aragement  of  the  writing  of  text-books  as  compared  to 
the  prosecution  of  reseaich  work,  but  of  the  intrinsic  Morth  of  a  text- 
book such  as  the  one  undei-  consideration  there  can  be  no  questiou.  Truly, 
as  great  a  service  as  that  of  pure  investigation  is  rendered  by  the  calm 
and  judicious  spirit,  who,  without  prejudice,  wisely  sifts  the  great  mavSs 
of  collected  investigations  and  brings  from  them  a  tangible  order  and 
scheme.  And  upon  such  a  service  rests  the  great  leputation  of  Ziegler's 
text-book. 

At.dred  Scott  Warthin. 

Ann  AunoK,  Miciik^an,  September,  1908. 

Note. — Because  of  tlie  difference  in  tlu;  size  of  the  page  it  has  been  found  necessary 
to  Hiduce  slightly  some  of  the  illustrations.  In  such  cases  the  magnification  or  ampli- 
fication has  been  changed  to  meet  the  amount  of  reduction. 


CONTENTS. 


PAOK 
TNTHoDrCTIOX,  ............  1 

('HA1'TI;H    I. 

EXTHINSIC    CaTSKS    and    CoXGEXITAL    AxLACiK    OF    DiSEASE. 

I.  The  Extrinsic  Causes  of  Disease.  ........       -1 

1.  The  Origin  of  Disease  through  Deficient  Supply  of  Tood  and  Oxygen. 

through  Fatigue.  Heat  and  Cold,  Changes  of"  Atmospheric  I'ressun' 
and  Electrical  Influences.  .         .         .         .         .         .         .  .4 

2.  The  Origin  of  Disease  through  Mechanical  Influences.  .         .         .     l(i 

3.  The  Origin  of  Disease  through  Intoxication,  .         .         .         .         .is 

4.  The  Origin  of  Di.sease  through  Infection  or  Parasitism.         .         .         .     ;i(t 
II.  Congenital  and  Inherited  Anlage  of  Disease,         .         .         .         .         .         .44 

1.  Immunity,  Predisposition,  and  Idiosyncrasy  .         .         .         .         .44 

2.  Diseases  Arising  from  Congenital  Pathological  Anlage,  .         .         .48 

CHAPTER   II. 

The  Spkead  and  Generalization  of  Pathological  Processes  throughott  the 
Organism.     Aittointoxications  and  Secondary  Diseases. 

I.  Cieneral  Consideration  of  the  Different  Forms  of  the  Distribution  and  Cen- 

eralization  o'  Pathological  Proces.ses  in  the  Organism,         .  .         .  OlJ 

II.  Metastases  and  Em])()Iism  and  Their  Significance  in  the  Development  of 

Lymphogenous  and  1  hematogenous  Disea.ses,         .....  (14 

III.  The  Sequehe  of  Local  Organic  Diseases,       .......  72 

IV.  Autointoxications  and  Disturbance  of  Internal  Ohind  Secretion,           .         .  7') 
V.  Fever  and  Its  Significance,           .         .         .         .         .         .         ;         .         .  ii(» 

CHAI'TF.Pv    III. 

The  Protective  and  Healixg  Foimes  of  the  Hi^max  Orgaxism.     The  Acijiiimng 

OF  Immtxity. 

I.  The  Natural  Protective  Contrivances,  Protective  Forces  and  Healing  Powers 

of  the  Human  Organism,  and  Their  Action.  ....  '.17 

II.  The  Acquiring  of  Immunity  against  Infectiotis  ;ind   Intoxic;itions.      Pro- 
tective Inoculation,        .         .  .         .         .  .  Ill 

III.  The    Active    Substances    of    Acquired    Immunity.     Ehrlidr's    Sidc-cli.iin 

Theor\',  .  .  .  .  .  .  .  .  .  .lis 

CHAPTEI?    IV 

DlSTrWHAXCES    IX   THE   ClIJCfLATTOX    OF   THE    BlOOD    AXO    OF   THE    LvMI'H. 

I.  General  Distiubances  of  the  Circulation  Dependent  upon  Cliangcs  inlhc 
Function  of  the  Heart.  Changes  in  the  General  Vascular  Piesist.-'.ncc. 
and  Changes  in  the  Mass  of  the  Blood, 124 


CONTEXTS. 


II.  Local  Hj'peraemia  and  Local  Anjpmia, 

III.  Coagulation,  Thrombosis,  and  Stasis, 

IV.  (Edema,        ....... 

V.  Ha-inorrhage  and  the  Formation  of  Infarcts, 

VI.  Lymphorrhagia,  ..... 


PAGE 

.  130 
.  135 
151 
.  158 
.   165 


CHAPTER    V. 

Retrograde  Disturb.\nces  of  Nutrition-  axd  Infiltrations  of  Tissues. 

I.  General  Considerations  Concerning  the  Retrograrle  Disturbances  of  Nutri- 
tion and  the  Tissue-infiltrations.     ........  167 

II.  Death  of  the  Organism 168 

III.  Necrosis  and  Gangrene,         .........  170 

IV.  Hypoplasia,  Agenesia,  and  Atrophy,    ...  ....  180 

V.  Cloudy  Swelling  and  Hydropic  Degeneration,       ......  190 

VI.  Lipomatosis,  Atrophy  of  Fat-tissue,  and  Fatty  Degeneration,      .         .         .  193 

VII.  The  Deposit  of  Glycogen, 204 

VIII.  Mucous  Degeneration,  ..........  207 

IX.  Formation  of  Epithelial  Colloid  and  Epithelial  Hyaline  Concretions,  .  209 

X.  The  Pathological  Cornification  of  Epithelium,      ......  212 

XI.  Amyloid  Degeneration  and  the  Amyloid  Concretions,  ...  21-1 

XII.  Hyaline  Degeneration  of  Connective  Tissue,  and  the  Hyaline  Products  of 

Connective-ti.ssue  Cells,  .........  222 

XIII.  Petrifaction  of  the  Tissues  and  the  Fonnation  of  Concretions  and  Calculi,  226 

XIV.  The  Pathological  Fomiation  of  Pigment 238 

XV.  The  Pathological  Absence  of  Pigment,  ......  257 

XVI.  The  Formation  of  Cysts, 258 


CHAPTER   VI. 

Hypertrophy  .\xd  Regeneration.     Results  of  Tr.\nsplant.\tiox.     Metaplasia. 

I.  General  Considerations  Concerning  the  Processes  Known  as  Hypertrophy 

and  Regeneration,  and  the  Accompanying  Cellular  Changes.         .         .  262 
II.  The  Processes  of  Hyperplasia  and  Regeneration  in  the  Various  Tissues,       .  285 

III.  The  Results  of  Transplantation  and  Implantation  of  Tissues  and  Organs,  309 

IV.  The  Metaplasia  of  Tissues,  . 314 

CH.\PTER    VII. 

I  N  F  L  A  M  :\I  a  T  I  O  N  . 

I.  The  Early  Stages  of  Acute  Inflammation,    .....  .         .  319 

II.  The  Termination  of  Acute  Inflammation  in  Healing,  ....  345 

III.  The  Inflammatory  New-formation    of   Tissue.    Healing   of   Wounds,  Sub- 

stitution of  Exudates  and  Tissue-necroses  ])y  Connective  Tissue,         .  350 

IV.  Chronic  Inflammations, 365 

CHAPTER    VIII. 

TUMOR.S. 

I.  General  Con.siderations.         .........  .  371 

II.  The  Different  Forms  of  Tumors, 385 

1.  Tumors  Derived  from  Connective  Tissue  or  the  Supjjorting  Framework, 

(a)  Fibroma,      ...........  385 

(b)  Myxoma 385 

(r)   Lipoma,        ...........  "S" 

(d)  Chondroma 389 

(e)  Osteoma, ■  .         .  391 


COXTKNTS.  IX 

PAGE 

(/')    Ihi'iiianiiioiiia  and   L\inpliai\>ri<)ina :{94 

(g)   Myoma.         .......                    ....  398 

('/O  Glioma  ami  Xcuiojilioma  C.aiviilioiiarc 400 

(,;■)    Neuroma  and  Xcurofilnoiii.i.                  .                   ....  4]::? 

(/.•)  Sarcoma.      .                   41  (i 

2.  The  Epithelial  Tumors 419 

((/)  General  Remarks.         .         .  439 

(b)  Papillary  I'lpillielioma.  Adenoma,  and  Cystadenoma.  .  .  440 

(c)  Carcinoma  and  ("ystoeareinoma.  ......  45") 

3.  The  Teratoid  Tumors  a"nd  Cysts.  485 


CHAPTER    IX. 

DlSTUKBANCES    OF    DEyELOPMENT    .\ND    THE    Re.SULTINCJ    M  ALFOHMATIONS, 

I.  General  Considerations  Regarding  Disturbances  of  Development   and  tlu 

Origin  of  Malformations .         .  498 

11.  The  Different  Forms  of  Malformations  in  Man,    ......  500 

1.  Arrests  of  Development  in  a  Single  Individual,     .  ...  500 

(a)  Arrest  of  the  Development  of  the  Entire  Embryonal  .Vnlage.     .  50f) 
(6)   Defective  Closure  of  the  Cerebrospinal  Canal  and  the  Accom- 
panying Malformations  of  the  Nervous  System,       .         .         .  508 
(c)   The  Malformations  of  the  Face  and  Neck,  .         .         .         .517 

{(l)  Faulty  Closure  of  the  Abdominal  and  Thoracic  Cavities  and  the 

Accompanying  Malformations.  ......  520 

{e)   Malformations  of  the  External  Genitalia  and  Anus,  due  to  Ar- 
rested Dev-elopment,         ........  523 

(/)    Malformations  of  the  Extremities,  due  to  Arrested  Development,  525 

2.  Abnormal  Position  of  the  Internal  Organs,    ......  530 

3.  ilalformations,  due  to  Excessive  Growth  or  Multijjlication  of  Organs 

or  Body-parts,  .........  531 

4.  True  and  False  Hermaphrodism,  .......  535 

5.  Double  Monsters,  .........  539 

(a)  Classification  of  Double  Monsters,         ......  .'iSO 

(6)  The  Chief  Forms  of  Double  Monsters, 540 


CHAPTER   X. 
The  Pathogenic  Fission -fungi  and  the  Diseases  Caused  by  Thk.m. 

I.  Cicneral  Considerations  Regarding  the  Schizomycetes  or  Fission-fvmgi.     .  549 

1.  General  Morphology  and  Biology  of  the  Fission-fungi,  .  .  .')49 

2.  General  Considerations  Concerning  the  Pathogenic  Schizomycetes  and 

their  Behavior  va  the  Human  Organism,     .     .         .         .  .  55S 

II.  Tlie  Different  Forms  of  Bacteria  and  the  Infectious  Diseases  Caused  by 

Them, ".  5(i:; 

1.  The  Cocci  or  Sphaerobacteria  and  the  Morbid  Processes  Caused  by  Tliem. 

(a)  General  Considerations  Regarding  the  Cocci,        ...  563 
(6)  Pathogenic  Cocci,         .........  565 

2.  The  Bacilli   and   the    Polymorphous    Bacteria   and   the    Pathological 

Proces.ses  Produced  by  Them,  ......  .')S() 

(a)  General  Considerations  Regarding  Bacilli  and  the  Polymorphous 

Bacteria, 586 

(b)  The  Pathogenic  Bacilli  and  Polymorphous  Bacteria,    .         .         .  .589 
3    The  Spirilla  and  the  Diseases  Caused  by  Them 670 

(«)  General  Remarks  uijon  th(>  Spiiill;i.      ......  670 

(6)  The  Pathogenic  Spirilla.        ........  671 


(•liAl'ri;i{    XI. 
The   Veasts  and  Mot-lds   and  the   1)isk\si;s   I'uonif  kd   hv  T 


CONTENTS. 


The  Animal  Paka? 
I.  Protozoa, 


CHAPTER    XII. 
AND  THE  Diseases  Produced  by  Them. 


II.  Vermes.     Worms 

A.  Platj'helminthes      Flat-Worms. 

1.  Trematoda.     Sucking-Worms, 

2.  Cestoda.     Tape-Worms, 

B.  Nemathelminthes.     Round-Worms, 
III.  Arthropoda.  ..... 

1.  Arachnida,    ..... 

2.  Insecta, 


Index, 


689 
716 
716 
716 
721 
734 
748 
748 
752 

757 


LIST  OF  ILLUSTRATIONS, 


PAGB 

1 .  Lightnino;-figures  on  the  shoulder,  breast,  and  arm 14 

2.  .Multiple  emboli  in  the  branches  of  the  pulmonar\-  arlciy 65 

A.  Fat-embolism  of  the  lungs 66 

4.  Fat-embolism  of  the  kidney 67 

5.  Thyreoprival  cachexia 82 

(i.  .Myxcedema S3 

7.  Sa'me  case  after  treatment  witli  thyroid  extract 8^ 

S.  Female  cretin S4 

9.  'romperatiu'e  chart  of  a  ct)ntimious  remittent  fever 91 

10.  Temperature  chart  of  a  continued  fever  with  rapid  rise  and  fall 92 

11.  Temperature  curve  of  an  intermittent  fever 92 

12.  Lardaceous  clot  from  the  cadaver 13") 

13.  Recent  hsemorrhagic  infarct  of  the  lung 136 

14.  Bimdles  and  stellate  clusters  of  fibrin  threads  or  rods 137 

] .5.  Red  thrombus 1 38 

16.  Laminated  mixed  tlu-ombus  rich  in  cells 139 

17.  White  thrombus  |)oor  in  cells 139 

1<S.  Rapid  l)lood-streani 140 

19.  IModerately  slow  blood-stream 140 

20.  Creatly  retarded  blood-stream 140 

21.  Polypoid  heart  thrombi 144 

22.  Thrombosis  of  femoral  vein 145 

23.  Remains  of  a  thrombus  of  femoral  vein 146 

24.  Obliteration  of  pulmonary  arteiy  by  connective  tissue 147 

25.  Remains  of  embolic  plugs  m  pulmonary  arteiy 147 

26.  Embolism  of  intestinal  artery  with  purulent  arteritis 148 

27.  Stasis  from  venous  hypersemia 150 

2S.  Stasis  oedema  of  the  papillary  bodies 152 

29.  Hj^dropic  connective-tissue  cells 152 

30.  (Edema  of  muscle 1 53 

31.  Inflammatory  oedema  of  the  papillary  bodies 153 

32.  Hiemorrliage  into  skin 159 

33.  Traumatic  cerebral  haemorrhage 160 

34.  Htemorrhagic  infarct  of  the  lung.         164 

35.  Necrosis  of  kidney  epithelium 171 

36.  Peiipheral  portion  of  an  ana?mic  infarct  of  kidney 172 

37.  Coagulation-necrosis  of  mesenteric  lymph-gland 174 

38.  Waxy  necro.sis  of  striped  muscle 175 

39.  Caseation-necrosis  of  tuberculous  focus 175 

40.  Fibrin-containing  tul)ercle  of  the  lung 176 

41.  Li([uefaction-necrosis 177 

42  Dry  gangrene  of  the  toes 178 

43.  Skeleton  ot  a  female  cretm,  thirty-one  years  of  age 181 

44  Skeleton  of  a  female  dwarf,  fifty-eight  years  of  age 181 

45.  Head  of  Helene  Becker  (microcephalia) 182 

46.  Brain  of  Helene  Becker 182 

47.  Hypopla.sia  and  microgyria  of  left  cereljral  hemisphere 182 

4.S.  Hypo]:)lasia  of  uterus 183 

49.  Hypoplasia  of  the  .small  intestine 183 

'iO.  Sections  of  ovary  at  different  ages 184 

51.  Juvenile  muscular  atrophy 185 

52.  Excentric  atrophy  of  lower  end  of  tibia  and  hl)ula 186 

53.  Senile  atrophy  of  .skull-cap 187 


LIST    OF    ILLUSTKATIONS. 


54.  Section  through  atrophic  muscle 187 

55.  Senile  atrophy  of  the  kidney 188 

56.  Arteriosclerotic  contracted  kidney 18S 

57.  Pressure-;itr()])hy  of  spinal  column 189 

58.  Hemiatropliia  facialis 189 

59.  Cloudy  swelling  of  liver-cells 190 

60.  Cloudy  swelling  of  kidney-cells 191 

61.  Hydropic  ilegeneration  of  carcinoma-cells 192 

62.  Hydrojnc  ilegeneration  of  muscle-fibres 192 

63.  Tnnisverse  section  of  hydropic  muscle 192 

64.  Fat  tissue  from  the  panniculus  of  the  heart 193 

65.  Lipomatosis  of  calf-muscles 194 

66.  Spinal  muscular  atrophy  with  lipomatosis 195 

67.  Skin  with  sweat-glands 195 

68.  Fatty  infiltration  of  liver 190 

69.  Fat-granule  cells 197 

70.  Fat-containing  liver-cells 199 

71.  Fatty  degeneration  of  heart-muscle 199 

72.  Anaemic  and  fatty  necrosis  of  the  myocardium 199 

73.  Fatty  degeneration,  vacuolar  degeneration  and  necrosis  of  heart-muscle 200 

74.  Marked  chronic  fatty  degeneration  of  heait 200 

75.  Fatty  degeneration  of  kidney  epithelium 201 

76.  Cholesterin  plates  and  margarin  needles 204 

77.  Glycogen  degeneration  of  the  renal  epithelium  in  diabetes 205 

78.  Mucoid  degeneration  of  epithelial  cells 207 

79.  Mucoid  degeneration  of  epithelial  cells,  from  a  cystadenoma  of  ovaiy 208 

80.  Mucoid  degeneration  of  connective  tissue 208 

81.  Colloid  degeneration  of  thyroid 209 

82.  Secretion  of  colloid  in  the  thyroid 209 

83.  Urinary  tul)ules  filled  with  colloid 210 

84.  Colloid  concretions 210 

85.  Hypertrophic  prostate  with  concretions 211 

86.  Amyloid  spleen 214 

87.  Amyloid  liver  treated  with  iodine 215 

88.  Amyloid  degeneration  of  splenic  follicles  and  splenic  ))ulp 216 

89.  Amyloid  liver 217 

90.  Amyloid  kidney 218 

91.  Corpora  amylacea 220 

92.  Hyaline  degeneration  of  the  connective  tissue  of  a  colloid  goitre 222 

93.  Hyaline  degeneration  of  connective  tissue  in  a  tuberculous  bursa 223 

94.  Hyaline  degeneration  of  blood-vessels 223 

95.  Hyaline  degeneration  of  the  connective  tissue  of  the  myocardium 223 

96.  Calcification  of  the  media  of  the  aorta 227 

97.  Calcification  of  the  media  of  the  femoral  artery 227 

98.  Calcified  cerebellar  vessels 228 

99.  Calcification  of  necrotic  lung 22S 

100.  Hyaline  degeneration  and  calcification  of  the  connective  tissue  of  the  renal 

papillffi. 229 

101.  Calcification  of  epithelium  of  minary  tubules 229 

102.  Concretions  of  lime  salts ' 230 

103.  Section  of  psammoma  of  dura  mater 230 

104.  Deposit  of  urates  in  knee-joint 231 

105.  Deposit  of  needle-shaped  crystals  of  sodimn  urate 231 

106.  Gouty  nodules  of  hand * 232 

107.  Faceted  stones  from  gall-bladder 233 

108.  Section  of  cholesterin  stone 234 

109.  Uric-acid  infarction  of  kidney 234 

110.  Coral-like  urinary  calculus 235 

111.  Calculi  of  sodium  urate  and  ammonium-magnesium  j^hosphate 235 

1 12.  Tncrusted  lead-pencil  from  bladder 236 

1 13.  Large  hairy  naivus  on  back  and  buttocks 238 

114.  Pigmenterl  cells  from  skin  in  Addison's  disease 239 

115.  Cells  containing  amorphous  pigment.     Crystals  of  ha^matoidin 243 

116.  Hsemosiderin-  and  ha^matoidin-containing  cells 244 

117.  Deposit  of  pigment-cells  in  a  lymph-gland 245 

118.  Infiltration  of  liver-rods  with  ha^mosiderin 246 


LIST    OF    ILLITSTHATIO.NS. 


119.  Hsemochromatosis  of  the  liver 247 

120.  Hteniosiderosis  of  tlie  bone-marrow 24S 

121.  Hienuitogenous  hieniosiderosis  of  kidney  of  pernicious  malaria 24!t 

122.  Icterus  of  liver  due  to  compression  of  common  duct 251 

123.  Icterus  of  kidney ~i^'-i 

124.  Deposit  of  cinnabar  in  tattoo 2.3.1 

125.  Aro:yria  of  rabbit's  kidney 250 

120.  Vitiligo  endemica 257 

127.  Multiple  cysts  in  epididymis 251) 

128.  Dilatation' cvst  of  pancreas 259 

129.  Hydrops  tuba> 260 

130.  Elephantiasis  femorum  neuromatosa 262 

131.  Elephantiasis  cruris  lymphangiectatica 263 

132.  Ichthyosis  congenita  (microscopical) 263 

133.  Ichthj'osis  congenita 264 

134.  Cornu  cutaneum  from  back  of  hand 264 

135.  Cornu  cutaneum  from  arm 264 

136.  Head  of  a  liearded  woman 265 

137.  Leontiasis  ossea 265 

138.  Hypertrophy  of  left  ventricle 267 

139.  Hypertrophy  of  incisor-tooth  of  a  white  rat,  due  to  distise 268 

140.  Elephantiasis  scroti 268 

141.  Acromegaty 269 

142.  Skeleton  of  hand  from  case  of  acromegaly 270 

143.  Cutaneous  portion  of  a  laparotomy  woimd 273 

144.  Healing  of  intestinal  ulcer 274 

145.  Scar  of  muscle  and  tendon 275 

146.  Edge  of  embolic  scar 276 

147-157.  Nuclear  changes  in  cell-division 280-282 

158.  Atypical  karyokinetic  figures 282 

159-162.  Giant-cells  from  an  osteosarcoma 283 

163.  Proliferating  adipose  tissue 283 

164.  Regeneration  of  the  epithelium  of  the  bile-ducts 286 

165.  Healing  blister 286 

166.  Development  of  blood-vessels 289 

167.  Two  vessels  of  papillary  body,  with  proliferation  of  endothelium 290 

168.  Proliferating  periosteum  four  days  after  fracture  of  bone 291 

169.  Isolated  cells  from  wound-granulation 292 

170.  Development  of  connective  tissue  from  fibroblasts 292 

171.  Scar  from  skin,  two  years  old 293 

172.  Periosteal  formation  of  cartilage 293 

173.  Endosteal  formation  of  bone  from  osteoblasts 294 

174.  Formation  of  osteoid  trabecula?  in  the  proliferating  periosteum 294 

175.  Formation  of  bone  upon  old  bone  by  deposits  of  osteoblasts 295 

176.  Section  from  a  germ-centre  of  a  mesenteric  lymph-gland 298 

177.  Regeneration  of  striped  muscle 301 

178.  Sclerotic  tissue  from  the  posterior  columns  of  spinal  cord 304 

179.  Old  and  newly  formed  nerve-fibres 305 

180.  Cross-section  of  nerve-bundle  from  median  nerve  four  months  after  wound.  .   305 

181.  Amputation-neuroma 306 

182.  Skin-transplantation  of  about  four  and  a  half  days 311 

183.  Periosteal  formation  of  bone 31.) 

184.  Formation  of  bone  from  connective  tissue 315 

185.  Periosteal  formation  of  cartilage 316 

186.  Tracheotomy  wound  in  cricoid  cartilage , 316 

187.  Metaplasia  of  cartilage  into  reticular  tissue 317 

188.  Metaplasia  of  cartilage  into  osteoid  tissue 317 

189.  Inflamed  human  mesentery 322 

190.  Meningitis  recens  purulenta 327 

191.  Haematogenous  staphylococcus  myositis 327 

192.  Section  through  the  edge  of  a  blister 328 

193    Parenchymatous  hepatitis 328 

194.  Mucous  catarrh  of  a  bronchus 329 

195.  Purulent  desquamative  catarrh  of  trachea 331 

196.  Catarrhal  secretions  of  different  nuicou.s  membranes .332 

197.  .\cute  hiemorrhagic-fibrinous  inflammation  of  trachea 333 


xiv  LIST    OF    ILLUSTRATIONS. 

PAGE 

198.  Croupous  membrane  from  trachea 333 

199.  Section  of  diphtheritic  membrane 334 

200.  Croupous  tracheitis 335 

201.  Traumatic  fibrino-puruient  peritonitis 335 

202.  Fibrinous  pleuritis 335 

203.  Fibrino-puruient  diplococcus  pleuritis 336 

204.  Croupous  pneumonia 337 

205.  Purulent  bronchitis,  peribronchitis,  and  peribroncliial  bronchopneumonia.  .  .  339 

206.  Section  of  a  small-pox  pustule 339 

207.  Embolic  abscess  of  intestinal  wall 340 

20S.  Suppuration  and  necrosis  of  the  mucosa  of  the  intestine  in  dysentery 341 

209.  Plilegmon  of  subcutaneous  tissue ' ' 342 

210.  Necrosis  of  the  epithelium  of  the  epiglottis 343 

211.  Bacillaiy  diphtheritis  of  colon  in  dysentent- 344 

212.  Section  of  uvula  in  diphtheria 344 

213.  Diphtheritic  necrosis  of  a  mesenteric  hnnph-irland 345 

214.  Phaeocytes  from  granulation  tissue 346 

215.  Isolated  cells  from  a  wound-granulation 350 

216.  Scar  tissue  fifteen  days  old 351 

217.  Tissue  from  a  scar  sixty-five  days  old 352 

21 S.  Plasma-cells  and  klasmatocytes 353 

219.  Dog's  hair  encapsulated  in  subcutaneous  tissue 353 

220.  Cross-section  of  blood-vessel  from  the  tleei)er  layers  of  the  skin 354 

221.  Granulation  tissue  from  open  wound 356 

222.  Healing  of  incised  wound  of  skin 358 

223.  Cutaneous  portion  of  a  laparotomy  scar 359 

224.  Beginning  organization  of  pericardial  exudate 360 

225.  Granulation-tissue  fonnation  on  the  pleura  in  jilem-itis 360 

226.  Organization  of  pericardial  e.xudate 361 

227.  Intraseptal  and  intra-alveolar  development  of  connective  tissue  in  the  lung.  .  361 

228.  Development  of  fomiative  tissue  in  a  thrombosed  femoral  arteiy 362 

229.  Edge  of  organizing  ha?morrhagic  infarct  of  lung 362 

230.  Fibroid  area  in  heart-muscle 363 

231.  Necrosis  in  lower  portion  of  femur 365 

232.  Changes  in  lung  and  pleura  in  chronic  jnirulent  jileuritis 366 

233.  Stone-cutter's  lung 367 

234.  Condyloma  acuminatum 367 

235.  Periosteal  hyperostosis  of  the  tibia 368 

236.  Section  through  mucosa  of  atrophic  colon 369 

237.  Induration  and  atrophy  of  kidney  tissue  in  chronic  nephritis 369 

238.  Hyperplasia  of  connective  tissue  and  proliferation  of  bile-ducts  in  chronic 

hepatitis 370 

239.  Tissue  from  mannnaiy  cancer  with  many  division-figures 372 

240.  Fungoid  carcinoma  of  body  of  uterus 373 

241.  Papilhny  adenoma  of  rectum 373 

242.  Primary  carcinoma  of  gall-bladder 377 

243.  Prnnary  carcinoma  of  liver 380 

244.  ^letastases  in  periglandular  lymph- vessels  of  axilla ly  region 381 

245.  Metastases  of  carcinoma  in  portal  vein  and  liver  capillaries 381 

246.  Metastatic  sarcoma  of  liver .• 382 

247.  Recurrent  sarcoma  of  femur 383 

248.  Hard  filiroma  of  ear-lobe 385 

249.  Section  ot  cpdematous  fibroma  of  uterus 385 

250.  Fibroma  pericanaliculare  niamnuo 386 

251.  Cells  from  a  myxoma  of  the  periostevuii 388 

252.  Section  of  a  myxosarcoma 38S 

253.  Lipoma  of  the  shoulder  region 389 

254.  Lipomyxoma  of  the  back 390 

255.  Periosteal  chondroma  of  finger-phalanx 391 

256.  Section  of  chondioma  of  libs 391 

257.  Chondromyxosarcoma  parotidis 392 

258.  Periostea!  "chondroma  of  calcaneus 392 

259.  Osteochondroma  of  humerus 393 

260.  Ivorj'^dike  exostosis  of  parietal  bone 394 

261.  Exostosis  cartilaginea  of  tibia 395 

262.  Ivory-like  osteoma  of  parietal  bone 396 


!.l:S'J'    OK     ILLISTH  A'llO.NS.  XV 

PAGE 

26:5.  Osteoma  of  diiia  lualcr ;i«»f> 

264.  O.steochouilrDina  of  iiumerus ;i07 

265.  Teleaiiiliectasi.s  of  abdominal  panniculus 39S 

266.  Dilated  capiliarie.s  from  a  teleangiectatic  tumor  of  the  brain 399 

267.  .Vnfiioma  cavorno.sum  cutaneum  congenitum 399 

26N.   Anirioma  caverno.sum  lu'patis 400 

269.  .Vnnionia  sim])lo.\  hypcrtrophicum 401 

270.  .\ngioma  .simplex  liypertrophieiiui  eutanenm  el  siibculaneum 401 

271.  Angioma  cavernosum  liypert  rophieum 402 

272.  Angioma  arteriale  plexiforme 403 

273.  We<'ping  .sul)epitlielial  iympliangioma  of  skin 404 

274.  Lympliangioma  cav(>rnosum  subcut.-ineuin 405 

275.  Large  i\-iiry  pigmented  na'\iis 406 

276.  Lymphangioma  iiy|)ert rophieum 406 

277.  Lymphangioma  liypert  rophieum 407 

278.  Section  through  two  jiajiiihe  of  a  Heshy  wart 407 

279.  Myoma  of  uterus ' 409 

280.  Angiomyoma  subcutaneum  dorsi 410 

281.  Cells  from  rhabdomyonuita 411 

282.  (liioma  cerebri " 413 

283.  Section  of  a  glioma  cerebri 414 

284.  Neuroglioma  ganglionare 415 

285.  Amputation  neuroma  of  .sciatic  nerve 417 

286.  Nerves  from  a  cirsoid  neuroma ; 418 

287.  Cirsoid  neuroma  of  .sacral  region 418 

2S,S.   Sarcoma  of  intermuscular  se|)ta  of  cervical  nuiscles 421 

289.  Lymphosarcoma  of  nasal  nnicosa 421 

290.  Large  round-celled  sarcoma  of  skin 422 

291 .  Sarcoma  of  mamma 422 

292.  Siiindle-cells  from  a  large  spindle-celled  .sarcoma  of  cheek 423 

293.  Cells  from  a  myelogenous  giant-cell  .sarcoma ; 423 

294.  Giant-cell  .sarcoma  of  upper  jaw 424 

295.  Endothelioma  of  pia  mater 426 

296.  Endothelioma  dune  matris 427 

297.  l'"ndothelioma  of  jjleura 427 

298.  iMidothelioma  of  mamma 428 

299.  Hiemangioendothelioma  of  kidney 429 

300.  Angiosarcoma  of  thyroid 430 

301.  Angiosarcoma  of  testicle 430 

302.  Chondrofibroma  of  parotid 431 

303.  Melanotic  alveolar  sarcoma  of  skin 432 

304.  Melanotic  sarcoma  of  skin 433 

•305.  Metastasis  of  a  melanotic  sarcoma  of  skin 434 

30(>.  Endosteal  osteosarcoma  of  the  himierus  434 

307.  Sarcoma  ossificans 435 

308.  Ostecjid  sarcoma  of  the  ethmoid  bone 435 

309.  Petrifying  large-celled  sarcoma  of  tibia 436 

310.  Section  of  a  psammoma  of  dura  mater 436 

311.  Myxoangiosarcoma  of  parotid 437 

312.  Papillary  epithelioma 439 

313.  Senile  horny  wart 440 

314.  Papillary  epithelioma  of  larynx 441 

315.  Papillary  epithelioma  of  bladder 441 

31().  Papilla^'  ei)ithelioma  of  bladder 442 

317.  .Vdenoma  tubulare  of  intestine 444 

318.  Atlenoma  tubulare  of  stomach 444 

319.  .Vdenoma  manuna'  tubulare 445 

320.  Adenoma  mamma-  ahfolare 445 

321.  Papillary  adenoma  of  the  kidney 446 

322.  Fibroma  intercanaliculare  mamma'   447 

323.  Section  of  cystadenoma  ovarii  pa|>illiferum 448 

324.  .Vdenocystoma  of  bile-ducts 449 

325-   Portion  of  a  nuiltilocular  adenocystoma  ot  the  ovary 449 

326.  Section  of  an  adenocystoma  of  testicle 449 

327.  Multilocular  adenocystoma  of  liver 450 

328.  Cystoma  of  kidney 450 


XVI  LIST    OF    ILLUSTRATIONS. 

PAGE 

329.  Adenocystoma  ovarii  partim  simplex  partim  papilliferum 451 

330.  Portion  of  an  adenocystoma  papilliferum  ovarii 451 

331.  Cystoma  papilliferum  ovarii 452 

332.  Papillary  adenocystoma  of  ovary 453 

333.  Intracanalicular  papillary  fibroma  of  mamma 454 

334.  Section  of  carcinoma  of  the  lip 461 

335.  Beginning  cancer  of  portio  vaginalis  uteri 462 

336.  Development  of  adenocarcinoma  of  colon 463 

337.  Developing  adenocarcinoma  of  stomach 463 

338.  Cystocarcinoma  of  mamma 464 

339.  Tubular  adenoma  of  mamma  with  beginning  carcinoma 464 

340.  Carcinoma  placentare  of  uterus 465 

341.  Horny  carcinoma  of  tongue 468 

342.  Carcinoma  of  skin 468 

343.  Adenocarcinoma  recti  tubulare 469 

344.  Adenocarcinoma  fundi  uteri 470 

345.  Carcinoma  simplex  mammse 470 

346.  Acinous  carcinoma  of  mamma 471 

347.  Tubular  scirrhous  cancer  of  breast 471 

348.  Segment  of  a  cancer  of  breast 472 

349.  Mucoid  carcinoma  of  breast 473 

350.  Development  of  a  mucoid  cancer  in  atrophic  gastric  mucosa 474 

351.  Carcinoma  mucosum  mammae 474 

352.  Carcinoma  with  hyaline  drops 475 

353.  Enlarged  hydropic  cancer  cells 475 

354.  Carcinoma  myxomatodes 476 

355.  Adenosarcoma  malignum  of  kidney 476 

356.  Cystocarcinoma  papilliferum  mammse 478 

357.  Cystocarcinoma  papilliferimi  ovarii 479 

358.  Papillary  cystocarcinoma  of  mammse 479 

359.  Colloid  carcinoma  of  thyroid 480 

360.  Section    of   enlarged    axillary   lymph-gland    with    beginning   metastases    of 

carcinoma 481 

361.  Metastatic  cancer-cell  in  liver-capillary 482 

362.  Metastatic  cancer  in  liver  from  primary  carcinoma  of  the  pancreas 482 

363.  Carcinoma  metastases  in  the  uterine  mucosa 483 

364.  Metastatic  carcinoma  in  the  diploe  of  the  skull-cap 483 

365.  Adenoma-like  snaring-off  of  portions  of  mucosa  of  small  intestine 487 

366.  Adenoma-like  remains  of  Wolffian  body  in  the  uterine  wall 488 

367.  Portion  of  the  wall  of  a  dermoid  cyst  of  the  ovary 490 

368.  Section  of  a  prominence  in  a  multilocular  dermoid 491 

369.  Congenital  adonecystoma  of  testicle 293 

370.  Teratoma  of  testicle 494 

371.  Malformation  of  head  due  to  amniotic  adhesion 499 

372.  Malformation  of  face  due  to  amniotic  adhesion 500 

373.  Hand  stunted  by  amniotic  adhesion 501 

374.  Deformity  and  stunting  of  hand  due  to  pressure 501 

375.  Lithopa'dion 507 

376.  Craniorachischisis 509 

377.  Spina  bifida  sacralis 509 

378.  Myelomeningocele  sacralis 510 

379.  Anencephalia  et  acrania 513 

380.  Cranioschisis  with  exencephalus 513 

381.  Partial  agenesia  of  the  cranium 513 

382.  Hydrencephalocele  occipitalis 514 

383.  Encephalomeningocele  nasofrontalis 514 

384.  Synophthalmus  or  cyclopia 515 

385.  Frontal  section  of  cranial  cavity  in  synophthalmus  microstomus 515 

386.  Wolf's  jaws 518 

387=  Agnathia  and  synotia 518 

388.  Hernia  funiculi  imibilicalis 521 

389.  Fissura  abdominis  et  vesicae  urinariae 522 

390.  Hypospadias 523 

391.  Epispadias 523 

392.  Complete  alisence  of  urethra  and  external  genitals     524 

393.  Amelus 526 


LIST    OF    ILLISTHATIONS.  xvii 

PAGE 

394.  Microim'lus 526 

Ii95.  Syinjjvis  apiis 526 

396.  Synipu^  dipus 526 

397.  Detect  of  femur  and  fibula 527 

398.  Perodactylisni  and  syndactylism 527 

399.  The  same  hand  illuminated  by  Roentgen  rays 527 

400.  Perochirus ' 527 

401    Skeleton  of  perochirus  527 

402.  Peropus 528 

403.  Skeleton  of  perojjus 528 

404.  Polydactylism 533 

40.^.  Polydactylism  of  new-born 533 

401).  Polydactylism  and  syndactylism  of  left  hand 533 

407.  Polydactylism  and  syndactylism  of  right  foot 533 

408.  Hermaiihrodismus  verus  lateralis 536 

409.  External  genitalia  of  a  female  pseudohermai)hrodite 537 

410.  Acardius  acephalus 540 

411.  Acardius  pseudoucormus 540 

412.  Pygopagus 542 

413.  Ischiopagus 542 

414.  Dicephalus  dibrachius  dipus 543 

415.  Diprosopus  distomus  tetrophthalmus  diotus  dibrachius 543 

416.  Craniopagus  parietalis 544 

417.  Cephalothoracojiagu^ • 544 

418.  Thoracopagus  tribrachius  tripus 545 

419.  Polymelos. 546 

420.  Polymelos 546 

421.  Pygopagus  parasiticus 546 

422.  Thoracopagus  parasiticus 546 

423.  Thoracopagus  parasiticus 547 

424.  Epignathus 547 

425.  Gelatin  plate  with  colonies  of  bacteria 561 

426.  Streptococcus  from  a  purulent  peritoneal  exudate 563 

427    Micrococcus-colonics  in  liver-capillaiy 563 

428.  Cocci  grouped  in  tetrads 563 

429.  Sarcina  ventriculi. 563 

430.  Streptococcus  tracheitis  in  scarlatina 566 

431.  Streptococcus  pyogenes  from  phlegmon  of  stomach 566 

432.  Streptococcus  erj'sipelatis  in  lymph-vessel 566 

433.  Section  of  skin  in  erysipelas  bullosum 567 

434.  Erysipelas  of  head  in  child  of  one  month 567 

435.  Beginning  streptococcus  phlegmon  on  trunk 568 

4.36.  Streptococcus  phlegmon  of  muscle 569 

437.  Streptococcus  infection  of  petrous  bone 569 

438.  Metastatic  luematogenous  streptococcus  ])neumonia 570 

439.  Parietal  endocarditis  of  left  auricle,  due  to  streptococci 571 

440.  Erj-thema  multiforme  cau,sed  by  streptococci 571 

441.  Marked  streptococcus  infection  of  kidney 572 

442.  Diplococcus  pneumoniae .« 575 

443.  Diplococcus  pneumonia  in  early  stage 576 

444.  Multiple  abscesses  of  skin  caused  by  .staphylococci 578 

445.  Miliary  abscesses  of  kidney  caused  by  staphylococci 579 

446.  Staphylococcus  osteomyelitis  of  the  calcaneus 580 

447  Gonococci  in  urethral  .secretion 582 

448.  Urethritis  gonorrhoica 582 

449.  Bacillus  subtilis  in  different  stages  of  development 586 

450.  Clostridium  butyricum 586 

451.  Anthrax-bacilli  in  liver  capillaries 590 

452.  Anthrax-.sporcs 590 

4.53.  Anthrax  pustule 591 

454.  Portion  of  anthrax  pustule,  containing  bacilli 591 

455.  Typhoid  bacilli  from  a  pure  culture 594 

456.  Typhoid  bacilli  with  fiagella 594 

457.  Typhus  abdominalis.     Section  of  Peyer's  patch 595 

458.  Tetanus  bacilli  with  terminal  .spores 603 

4.59.  Bacillus  pneumonia- 606 


xviii  LIST    OF    ILLFSTHATIOXS. 

PAGE 

460.  Nail-shaped  stal)-culUire  of  pneumonia-Iiacilli  in  gelatin 606 

461.  Influenza-bacilli  from  sputum 607 

462.  Diphtheria-l)acilli  from  a  p\u-e  culture 609 

463.  Pest-bacilli 612 

464.  Tubercle-bacilli 615 

465.  Tubercle  from  a  fungoid  granulation  tissue  of  bone 616 

466.  Giant-cell  containing  tubercle-bacilli 616 

467.  Tuberculosis  of  pleura 617 

468.  Large-celled  tubercle  with  fibrin 617 

469.  Caseous  necrosis  of  tuberculous  granulation  tissue 618 

470.  Miliary  tubercle  of  omentiun 618 

471.  Fibrocaseous  tubercle  of  lung 619 

472.  Fibrous  tubercle  in  thickenefl  synovial  membrane 619 

473.  Lupus  of  skin  with  atyjncal  ]:)rolife ration  of  epitheliiun 626 

474.  Tuberculous  granulation  tissue  from  the  syno^•ial  membrane  of  the  knee  ....  627 

475.  Large  solitary  tubercle  of  pia  mater  cerebelli 627 

476.  Tuberculous  induration  of  the  lung 628 

477.  Tuberculous  induration  of  the  lung 628 

478.  Encapsulated  caseous  focus  in  hmg,  with  induration 629 

479.  Encapsulated  caseous  focus  in  lung 629 

480.  Tuberculous  cavity  in  tibia 630 

481.  Tubercuhnis  ulcer  of  intestine 631 

482.  Beginning  jiulmonaiy  tuberculosis  without  catarrh 631 

483.  Beginning  jjulnionary  tul)erculosis  in  child  of  two  years 632 

484.  Eruption  of  tubercles  in  a  lymph-glantl 633 

485.  Tuberculosis  of  veins  in  neighborhood  of  a  tuberculous  retroperitoneal  gland  634 

486.  Ha^matogenous  miliary  tuberculosis  of  liver 635 

487.  Tuberculosis  of  omentum 635 

488.  Proliferation  of  pleura  in  "  pearl-disease  "  of  cattle 637 

489.  Initial  sclerosis 642 

490.  Section  of  syphilitic  initial  sclerosis 642 

491.  Condyloma  latum  ani 643 

492.  Meningoencephalitis  sj^philitica  gummosa 644 

493.  Syphilis  of  the  skull-cap 644 

494.  Gumma  hepatis 646 

495.  Syphilitic  ulceration  of  larynx 647 

496.  Congenital  sy|)hilitic  induration  of  liver 647 

497.  Changes  in  lung  in  congenital  syphilis 648 

498.  Tissue  from  a  leprous  nodule 650 

499.  Giant-cell  containing  lepra-bacilli 650 

500.  Section  of  leprous  nodule  of  skin 650 

501.  Leontiasis  leprosa 651 

502.  Lepra  ana'sthetica  ulcerosa 652 

503.  Lepra  ansesthetica  mutilans 653 

504.  Glanders  of  cat's  testicle 655 

505.  Section  of  rhinoscleroma 658 

506.  Hyaline  cells  and  spherules  from  rhinoscleroma 658 

507.  Actinomyces  hominis 660 

508.  Actinomycosis  of  the  tongue 660 

509.  Actinomyces  druse  surrounded  by  giant-cells  and  pus-corpuscles 660 

510.  Actinomycosis  of  lung 661 

511.  Frontal  section  of  nose  and  upper  jaw  of  a  cow  affected  with  actinnmycosis.  .  662 

512.  Spirillum  rugula  and  spirillum  undula 670 

513.  Cholera-spirilla 671 

514.  Stab-culture  of  cholera-spirilla  in  gelatin 673 

515.  Stab-culture  of  the  Finkler-Prior  spirillum 675 

516.  Saccharomyces  ellipsoideus 678 

517.  Fresh  favus-mass  consisting  of  hyphse 678 

518.  Thrush,  from  tongue  of  man  dying  of  typhoid  fever 678 

519.  Section  througli  ;;  tluush-covered  oesophagus  of  a  small  child 679 

520.  Mucor  coiyml)ifer  in  fructification 681 

521.  Hypha;  of  Aspergillus  fumigatus,  with  conidia-bearers 681 

522.  Culture  of  Tricophyton  tonsurans 687 

523.  Amoeba  coli  mitis 689 

524.  Amoeba  dysenteric 690 

525.  Cercomonas  intestlnalis 601 


LIST    OF    ILLrsiKATlONS. 


526.  Trichomonas  hoininis (iiil 

527.  Trichomonas  vaginaUs liOl 

528.  Lamhlia  intestinahs d'.tL' 

529.  Spirocha^te  obermeieri  from  tho  l)loo(l  of  a  patient  sufferin<i  with  r('la|>.sin;r 

fever (i'.t:; 

530.  Portion  of  tissue  and  isolated  cells  from  a  splenic  follicle  in  case  of  typlius 

recurrens (i!);; 

5;U.  Trypanosoma  .sansiuinis  murium ()<»() 

532.  Trypanosoma  Lewisi  in  various  stages  of  development ()<»(i 

533.  Section  of  a  bile-duct  filled  with  coccidia 701 

534.  Coccidia  from  the  bile-ducts  of  a  rabbit's  liver 701 

535.  ICtiithelioma  conta^iosum 702 

536.  Parasites  of  epithelioma  contagiosum 703 

537.  ^liescher's  sacs  from  muscle  of  hog 703 

538.  Cycle  of  develoimient  of  Coccidium  schubergi 701 

539.  Plasmodivmi  malariiv  of  quartan  fever 7()S 

540.  Plasmodiiun  vivax  of  vernal  tertian  fever 709 

541.  Plasmodium  praecox  of  tropical  malaria 709 

.542.  Anopheles  claviger 710 

.543.  Ookinete  of  pernicious  malaria  in  intestinal  wall  of  mo.scpiito 710 

544.  Oocyst  of  pernicious  malaria,  filled  with  sporozoites 711 

545.  Cycle  of  development  of  Proteosoma  713 

.546.  Balantidium  coli 715 

547.  Di-stoma  hepaticum 717 

548.  Eggs  of  Distoma  hepaticiun 717 

,549.   Development  of  the  liver-fluke 718 

550.  Distoma  lanceolatum 718 

551.  Distoma  spathulatmn '. 719 

552.  Distoma  westermanni 719 

.553.  Distoma  htematobium 720 

554.  Eggs  of  Distotna  haematobium 720 

555.  Head  of  Taenia  soliimi 722 

556.  Half-ripe  and  ripe  segments  of  Taniia  solium 722 

557.  Two  proglottides  with  uterus 722 

558.  Segment  of  Taenia  .solium,  with  mature  sexual  apjjaratus 723 

.559.  I'^ggs  of  Ta^iia  solium • 723 

560.  Cysticercus  cellulosie 723 

.561.  Cysticerci  of  Tienia  solium 724 

562.  Portion  of  a  Taenia  saginata 725 

563.  Head  of  Tienia  saginata 725 

.564.  Segment  of  Taenia  .saginata 725 

.565.  Matm-e  Taenia  echinococcus 72S 

.566.  Wall  of  echinococcus  cyst  with  brood-cap.sules 728 

.567.  Echinococcus  hydatidosus 729 

.568.  Portion  of  an  Echinococcus  multilocularis 730 

.569.  Bothriocei)halus  latus ; 732 

.570.   Head  of  Bothriocephalus  latus 732 

571.  Middle  portion  of  a  proglottis  of  Bothriocephalus  lalus 733 

.572.  Eggs  of  Bothriocephalus  latus 733 

573.  Free  embryo  of  Bothriocephalus  latus 73.'> 

.574.  A.scaris  lumbricoides 735 

575.  Egg  of  Ascaris  lumbricoides 735 

576.  Oxyuris  vermicularis 737 

577.  Eggs  of  Oxyuris  vermicularis 73S 

578.  Male  of  Anchylostoma  duodenale : 739 

.579.  Head  of  Anchylostoma  duodenale 739 

580.  Eggs  of  Anchylostoma  duodenale 739 

.581.  .Vnguillula  inte.stinalis 74  1 

582.  Female  of  Anguillula  stercoral:  ; 741 

.583.  Triocephalus  (lispar 743 

.584.  Egg  of  Tricocephalus  dispar 74:; 

.58.5.  Sexually  mature  trichina' 744 

.586.   Encapsulated  muscle-trichina' 745 

587.  Filaria  or  Dracunculus  medinensis 746 

588.  Embryo  of  Filaria  bancrofti,  known  as  Filaria  .sanguinis  hominis 746 

589.  Female  itch-mite 749 


XX  LIST    OF    ILLUSTRATIONS. 

PAGE 

590.  Scabies 749 

591.  Leptus  autumnalis 750 

592.  Acarus  foUiculorum  hominis 750 

593.  Ixodes  ricinus 750 

594.  Cephalic  end  of  Pentastoma  denticulatum 750 

595.  Male  of  Dermatophagus  communis 752 

596.  Male  of  Dennatocoptes  communis 752 

597.  Female  of  Pediculus  capitis 753 

598.  Male  of  Pediculus  pubis 753 

599.  Female  of  Pediculus  vestimentorum 753 

600.  Larva  of  Anthomia  canicularis 753 

601 .  Larva  of  Musca  vomitoria 753 

602.  Larva  of  Lucilia  macellaria 753 

603.  Larva  of  Dermatobia  cyaniventris 753 

604.  Gastrophilus  equi 754 


GENERAL    PATHOLOGY. 


INTRODUCTION. 

The  life  of  an  organism  is  revealed  only  through  its  vital  manifesta- 
tions and  activities.  Physiology,  the  science  of  the  normal  or  healthy 
life,  teaches  ns  concerning  these  activities.  At  the  same  time  it  shows 
us  that  the  vital  functions  are  performed  according  to  detinite  laws  hav- 
ing their  foundation  in  the  structure  of  the  organism.  Changes  in  this 
organic  structure,  manifesting  themselves  in  vital  phenomena  (lijf'erinf/  from 
those  rec/arded  as  normal,  form  the  material  basis  of  disease  or  abnor- 
mal life.  The  return  to  the  normal  condition  is  regarded  as  the  sign  of 
recovery  or  healing. 

A  permanent  cessation  of  all  vital  functions  leads  to  death.  Tem- 
porary interruptions  of  the  vital  activities  without  the  loss  of  the  possi- 
bility of  a  return  to  the  normal  state  may  be  seen  in  the  condition  of 
apparent  death  or  in  congelation,  which  may  be  followed  either  by  death 
or  by  a  return  to  life  (anabiosis). 

When  there  are  present  pathological  changes  in  the  tissues,  arising 
either  before  the  appearance  of  pathological  symptoms  or  persisting  after 
their  cessation,  so  that  at  any  time  a  new  outbreak  of  the  latter  may  take 
place,  the  disease  is  spoken  of  as  latent. 

The  entire  science  of  disease  is  embraced  by  Pathology.  As  its  first 
task  there  falls  to  it  the  determination  of  the  causes  and  orif/in  of  pathologi- 
cal processes,  these  two  divisions  constituting  etiology  and  pathogenesis. 
A  second  task  lies  in  the  investigation  of  the  anatomical  changes  nnder- 
lying  the  pathological  alterations  of  function;  and  the  branch  of  the 
science  to  which  this  field  is  assigned  is  known  as  pathological  anatomy 
or  anatomical  pathology.  Siiu'e  the  structui-e  and  linei-  oiganization  of 
the  diilVrent  tissues  vaiy  accoi'ding  to  theii'  functions,  and  as  we  cannot 
conceive  of  \  ital  manifestations  wiihout  a  mateiial  substratum  for  them, 
it  is  reasonable  to  assume  that  pathological  manifestations  of  life  must 
likewise  be  the  expression  of  material  changes  in  the  tissues  concerned. 
Moreover,  experience  has  taught  us  that  in  the  case  of  any  pathological 
alteration  of  function  of  any  tissue  or  organ,  there  may  be  demonstiated 
in  the  latter  changes  of  structure,  in  ])art  e\-en  macioscojjically,  while  at 
other  times  they  can  be  made  out  only  Avitli  the  aid  of  the  microscope 
and  by  means  of  especial  histological  methods  of  investigation. 

A  third  field  of  labor  belonging  to  })atliology  is  concerned  with  the 
observation  and  interpretation  of  the  .si/mptoni.s  of  disease  as  seen  in  the  jxifient, 
and  this  branch  of  gcnci'al  pathology  is  designated  clinical  pathology, 
pathological  physiology,  physiological  or  biological  pathology,  lis  facts 
are  ascertained  in  part  bysimi)le  obser\ation  and  examination  of  the  pa- 
tient, and  in  part  through  the  utilization  of  especial  i)hysical  and  chemical 


INTRODITCTIOX. 


laethods  c.f  e-camination.  A  successful  applica  ion  of  the  results  obtamed 
by  the  methods  of  clinical  or  biological  pathology  requires  m  the  hrst 
Sace  a  knowledge  of  the  pathoIogical=anatomical  changes  present,  as 
well  as  of  their  etiology  and  pathogenesis.  As  a  further  help  to  the  m- 
Terpretat  on  of  disease  a  knowledge  of  the  chemical  processes  t^^nng  place 
XflMno  organism  under  the  influence  of  the  vital  acti^ty  of  the 
eel  s  and  the  u  iformed  ferments  separable  from  them  is  essentia  This 
knoXoe  I  specialized  in  the  science  of  pathological  chemistry  or 
chemiSr  pathology.  In  conjunction  with  anatomical  pathology  this 
fielTorpa^hology  offers  the  possibility  of  a  complete  understanding  of 
fhe  origin  and  cSurse  of  pathological  processes,  as  well  as  of  their  natm^e 

^^^Ti1xtensh-e  and  many-sided  domain  of  Pathology  demands  its 
practical  division  into  various  branches  according  to  especial  points  of 
?L^       A  knowledge  of  cluM  pathology  is  best  gained  at   he  bedside  or 

uThe  clinic  and  f?om  especial  courses,  lectures,  and  text-books,  l.^^.^- 
^i^chMpamiogy  demands  an  especial  theoretical  and  practical 
Snin-      Ii  this  text-book  General  Pathology  will  be  considered  as 

nXS^g  itiology,  pathogenesis,  and  Pfhological  anatomy  CV.^^^^^^^ 
cal  PatholoaiJ  will  be  touched  upon  only  m  so  far  as  i^,  nece^sarj 
To  i(ful^^l^i^n^^^g  of  the  anatomical  changes  occurring  m  diseased 

"""^The  first  part  of  the  work,  General  Anatomical  Pathology,  concerns 
itseK  with  the  causes,  origin,  nature,  and  course  of  disease -processes 
Sthout  reference  to  the  individual  clinical  forms  of  disease.  In  the 
reconTpairir^  Anatomical  Pathology,  the  pathological  processes 
occurrin^V;  the  individual  organs  and  tissues  are  considered  with  especml 
Sence^p  the  anatomical  and  histological  changes  occurring  m  them. 

Literature. 

{Pathological  Anatomy  and  Chemistry.) 

BirctmrscMemf^^^^^^^^^  1896-1897;    Mgem.    Pathologie,  Leipzig, 

Bollinger:  Atlas  und  Gnmdriss  d.pathoL  AnatomieAIunchen.  1896-1897. 
Bouchard-   Traite  de  pathologie  generale,  Pans,  189o-1901. 
?Santemesse  et  Podwyssowzki.Les  Processus  generaux,  Par:.,  1901. 
Coats:    Manual  of  Pathology.  London.  189o. 
finvne-     \natomie  pathologique.  Pans.  IJU^.       ,      .     ^     ,.      -.^qo 

HaUo^eau  «  Apart:  Trai.e  eMmen^ire  de  pa.holope  geaerale,  Paris,  1904. 
f-^l.:r°'St''lISSrpaS^"".-i^i..  Par..  l«n-1889. 


INTRODUCTION.  3 

Lazarus-Barlow:    A  Manual  of  r,i>noral  Patliolo.ixy.  London,  1899. 

Liikjanow.    Cnnulziisc  einor  alliionuMiien  PatlioloiiiediM-  Zelle,  Leipzis;,  1891;  Grund- 

/Aiixc  oiner  alliicnieinen   I'atlioloiiie  des  (U'fass.systonis,  Leipzig,  1894;    Cirundzi'ige 

einor  allgcnR'inen  Pathologic  dor  W-nlauung,  Leipzig,  1899. 
Neumeister;    Physiologische  Cheniie,  Jena.  1897. 

Nicolle-Diinschmann:    (Jnindziige  d.  all.irenieinen  Mikrobiologie,  Berlin,  19().'l 
V.  Noorden:    Pathologie  des  Slol't'wechsels,  Berlin,  189^5. 
Orth     Lehrlnich  der  speciellen  pathologiselien  Anatoniie,  Berlin,  1893-1903. 
von  Recklinghausen,   ^-yigcnieine   Pathologie   des  Kreislaufs  u.   der     Ernidirung, 

Stuttgart,  1883. 
Ribbert:    Pathologische  Histologic,  Bonn,   1901;    Die  Lehre    von  dem  Wesen   der 

Krankheit  in  ihrer  geschichtlichen  Entwickelung,  Bonn,  1899;  Specielle  Pathologie, 

Leipzig,  1902. 
Rumpel  uiul  Kast:    Pathologisch-anatomische  Tafeln,  Hamburg,  1892-1903. 
Schmaus:    Gnuulriss  der  patliologisclien  Anatoniie,  Wiesbaden,  1904. 
Stengel.    Text-liook  of  Pathology,  Philadelphia,  19()(). 
Thoma:    Lehrlnich  der  patholog.  An;itoniie,  Stuttgart,  1894. 
Tripier:  Traite  d'anatoniie  pathol.  generale,  Paris,  1904. 
Virchow:    Die  Celhilarpathologie,  Berlin,  1871. 

Weichselbaum:    Grumlriss  der  pathologiselien  Histologie,  Wien,  1892. 
Wells:    Chemical  Pathology,  Philadelphia,  1907. 
Woodhead:    Practical  Pathology,  London,  1892. 


CHAPTER  I. 

The  Extrinsic  Causes  and  the  Congenital  Anlage  of 

Disease. 

I.  The  Extrinsic  Causes  of  Disease. 

1.  Origin  of  Disease  through  Deficient  Siipphj  of  Food  and  Oxygen,  through 
Fatigue,  Heat  and  Cold,  Changes  of  Atmospheric  Pressure,  and  Electrical 
Influences. 

§  1.  From  his  birth  to  his  death  man  is  coustautly  exposed  to  the  in- 
flueuces  of  the  world  surrounding  him,  many  of  these  external  influences 
being  favorable  to  the  normal  exercise  of  his  functions,  while  others  are 
unfavorable. 

As  long  as  the  human  organism  is  able  to  offset  these  influences, 
through  independent  changes  of  its  relations  to  the  external  world  or 
through  adaptation  of  its  functions  to  external  conditions,  it  will  remain 
in  health.  If  his  regulating  mechanism  no  longer  suffices  for  successful 
opposition  to  unfavorable  external  influences,  and  if  he  cannot  escape 
these  or  change  his  conditions  of  life,  man  becomes  ill  or  dies. 

For  its  preservation  the  body  needs  first  of  all  a  certain  amount  of 
food,  water,  and  oxygen ;  and  though  it  may  exist  for  a  short  time  with- 
out these,  an  insufficient  supply  of  oxygen,  food  or  water  beyond  a 
certain  limit  and  after  a  certain  time  must  of  necessity  lead  to  disease 
or  death. 

A  total  deprivation  or  diminution  of  the  supply  of  oxygen  to  the 
tissues  may  take  place  at  any  period  of  life,  either  because  of  a  lack  of 
oxygen  in  the  surrounding  medium,  or  some  obstruction  to  the  entrance 
of  the  oxygen  of  the  air  into  the  lungs  or  blood,  or  inability  on  the  part 
of  the  blood  to  take  up  a  sufficient  amount  of  oxygen.  The  foetus  in 
idero  may  be  insufficiently  supplied  with  oxygen  as  a  result  of  diminished 
supply  to  the  mother,  pi'emature  separation  of  the  placenta,  disease  of 
the  placenta,  or  compression  of  the  cord,  whereby  the  interchange  of 
gases  between  the  maternal  and  foetal  blood  is  hindered.  After  birth  an 
insufficient  supjdy  of  oxygen  may  be  due  to  hindrances  to  respiration, 
or  the  child  may  be  so  weak  that  its  respiratory  movements  are  insuffi- 
cient to  expand  the  lungs. 

When  the  supply  of  oxygen  is  completely  shut  off,  as  may  happen 
from  the  entrance  of  water  or  other  fluid  into  the  respiratory  tract  or 
from  closure  of  the  air-passages,  the  affected  individual  dies  in  a  very 
short  time  from  choking  or  suffocation.  Animals  confined  in  closed 
chambers  die  as  soon  as  the  oxygen  of  the  air  reaches  two  or  three  per 
cent  by  volume,  the  normal  volume  percentage  being  20. S  (CI.  Bernard, 
P.  Bert). 

If  the  suj^ply  of  oxygen  is  not  wholly  shut  off",  but  only  greatly 
diminished,  as  in  the  case  of  carbon-monoxide  poisoning,  in  which  the 
firm  combination  of  carbon  monoxide  with  the  haemoglobin  prevents  the 
taking  up  of  oxygen  by  the  red  blood-cells,  death  by  suffocation  may 

4 


DEPRIVATIOX    OF    OXYGEX,    FOOD,    AM)    A\  ATKK.  5 

take  place  only  after  several  days.  In  giadnally  increasing;-  liindiances 
to  the  entrance  of  oxygen  and  resulting  accuniulation  of  carbonic  acid 
in  the  blood,  as  in  cases  of  narrowing  of  the  lumen  of  the  hirynx  thiongh 
inflaniinatory  exudates,  compression  of  the  trachea  from  goitre,  -weaken- 
ing or  obstruction  of  respiration,  etc.,  a  condition  of  breathlessness, 
cyanosis,  convulsions,  and  disturbances  of  consciousness  is  produced, 
which  is  termed  asphyxia. 

If  the  taking  up  of  oxygen  is  diminished  in  only  a  slight  degree  but 
for  a  long  time,  as  in  the  case  of  a  lessened  number  of  red  blood-cells 
in  oligocytha^mia,  degenerative  i)rocesses  characterized  by  increased  de- 
struction of  albumin  and  by  fatty  changes  may  occui-  in  the  tissues  and 
organs,  and  these  may  lead  not  only  to  disease  but  under  certain  condi- 
tions to  death. 

Total  deprivation  of  food  and  water  leads  to  a  ra])id  loss  of  body- 
weight,  inasmuch  as  the  fat  and  albumin  continue  to  be  decomposed; 
death  tinally  ensues.  According  to  Lehmann,  Miiller,  Munk,  Senator, 
and  Zuntz,  the  total  amount  of  oxidation  in  cases  of  starvation  does  not 
fall  below  that  of  the  same  individual  in  the  fasting  state  under  the 
same  conditions.  A  marked  decomposition  of  albmnin  and  loss  of  water 
take  place.  In  animals  death  occurs  after  the  loss  of  about  fortyjicT  cent 
of  the  body-weight,  about  one-half  of  the  loss  being  due  to  the  waste  of 
muscle. 

The  fat  disappears  mostj^apidly ;  even  as  much  as  ninety-three  per 
cent  may  be  lost.  The  other  organs  show  dimiuution  of  substance  in  tlie 
following  order:  liver,  spleen,  testicles,  muscles,  blood,  intestines,  skin, 
kidneys,  and  lungs.  The  h-ait,  nervous  system,  and  bones  show  the 
least  loss  of  weight ;  but  dest  luotion  of  bone-tissue  does  take  place  during 
starvation,  as  is  sliOMii  by  the  increase  of  calcium  and  phosphoric  acid 
in  the  urine,  following  ingestion  of  water.  In  the  blood  there  is  a  rapid 
diminution  of  the  leucocytes  (Luciani) ;  the  red  blood-cells,  on  the  other 
hand,  may  be  relatively  increased  in  number.  The  organs  of  animals 
dying  from  starvation  show  simi)le  atrophy  of  the  tissue-elements,  par- 
ticularly of  the  liver  (Lukjanow),  hyperemia,  scattered  hemorrhages, 
degenerations,  and  inflammatory  changes,  especially  in  the  intestine, 
liver,  kidneys,  and  nervous  system. 

In  the  case  of  total  deprivation  of  food  and  water,  death  occurs  in 
man  after  from  seven  to  twelve  days;  bodily  exercise  hastens  the  end, 
ingestion  of  water  may  delay  it  markedly,  so  that  some  indi^'iduals  have 
been  enabled  through  the  use  of  water  to  endure  a  period  of  total  absti- 
nence from  food  for  thirty  days  or  longer,  without  dying  oi-  suff«'ring 
permanent  harm.  The  consumption  of  Mater  leads  to  an  increased  ex- 
cretion of  nitrogen  in  the  mine. 

Life" may  be  maintained  for  a  long  time  upon  insufficient  nourish- 
ment, but  a  wasting  of  the  body  takes  place  w^hich  may  lead  to  a  condi- 
tion of  extreme  emaciation,  marasmus,  or  cachexia,  and  finally  to  death. 
The  same  thing  happens  when  the  com])Osition  of  the  food  is  unsuitable 
and  oidy  a  portion  of  the  necessai-y  food-elenuMits  is  ])i'esent  in  suHicient 
amount,  so  that  the  body  is  starved  <'illi('r  in  albumin,  fat,  sails,  or 
water.  Dogs  deprived  of  all  nitrogenous  food  die  in  from  thirty-one 
to  thirty-four  days  (Magendie).  Wh<Mi  the  food  is  abundant  but  i)0()r  in 
albumin,  there  occur  after  a  time  (in  dogs  aftei-  six  M'e<'ks)  loss  of  jippc- 
titeand  repugnance  toward  the  ]>roff<'r<'(l  food,  with  imi)airm('nt  of  diges- 
tion and  assimilation  (Munk).  This  is  especially  the  case  when  the  food 
Is  lacking  in  fat,  less  so  wlien  albumin  or  the  carbohydrates  are  wanting. 


6  THE    EXTRINSIC    CAVSES    OF    DISEASE. 

It  is  very  probable  that  the  lessened  absorption  is  chietly  due  to  diminished 
secretion  of  the  digestive  juices,  this  being  capable  of  quantitative  de- 
monstration in  the  case  of  the  bile.  The  fteces  are  finally  nearly  desti- 
tute of  bile. 

An  insufficient  supx)ly  of  iron  for  a  long  period  gives  rise  to  anaemia 
and  general  disturbances  of  nutrition. 

If  for  experimental  purposes  an  animal  well  supplied  with  food  is  to= 
tally  deprived  of  water,  there  is  a  rapid  loss  of  body-weight  followed 
in  from  eight  to  twelve  days  by  death.  The  pathological  changes  found 
in  the  different  organs  are  similar  to  those  resulting  from  starvation. 
They  are  caused  partly  by  lack  of  water  and  insufficient  absorption  of 
food,  and  partly  by  the  retention  of  harmful  products  of  metabolism. 

Cow's  milk  has  a  very  small  iron-content.  According  to  Flirst,  milk  ash  contains 
0.53  per  cent  of  iron,  white  of  egg  0.57,  beef  0.7,  peas  0.88,  potatoes  1.18,  apples  1.4, 
yolk  of  egg  1.65,  lentils  2.0,  plums  2.54,  rye  flour  2.54,  spinach  3.35,  lettuce  5.31, 
strawberries  5.89,  tea  9.29,  beef  blood  9.79  per  cent. 

Literature. 

(FesuJts  of  Diminished  Supply  of  Oxygen,  Food,  and  Water.) 

Ah-lfeld:  Der  Uebergang  der  iutrauterinen  Athmung   zur  extrauterineu,    IMarburg, 

1891. 
Beneke :  Grundlinien  der  Pathologic  des  Stoffwechsels,  Berlin,  1874. 
Bischoff  und  Volt:  Die  Gesetze  der  Ernahrung  des  Fleischfressers,  1860. 
Coen:    Sull'  iuanizione  acuta.     Bull,  delle  Scienze  Med.  di  Bologna,  ser.  vii.,  vol.  i., 

1S90. 
Daddi  et  Treves  :  Observations  sur  I'asphyxie  lente.    A.,  ital.  de  biol.,  xxviii.,  1897. 
Dennig:  Bcdeutung  der  Wasserzufuhr  flir  den  Stoffwechsel.    Zeit.  f.  Ther.,  i.,  1898. 
Dreyfus-Brissac :  De  I'asphyxie  nou  toxiquc,  Paris,  1883. 
Ehrlich:  Das  Sauerstoifbedurfniss  des  Organismus,  Berlin,  1885. 
Frankel:  Eiuliuss  d.  verminderten  Sauerstoffzufuhr.     Virch.  Arch.,  67  Bd.,  1876. 
Halliburton :  Lehrb.  der  chemischen  Physiologic  und  Pathologic,  Heidelberg,  1896. 
Hofmann:  Lehrbuch  der  gerichtl.  Medicin,  Wien,  1895. 
Hoppe-Seyler:  Stoffwech'sel  bei  Sauerstoffmangel.     Festschr.  d.  Assist,  f.  Virchow, 

Berlin,  1891. 
Krehl:  Die  Athinung.     Puthol.  Physiologic,  Leipzig,  1898. 
Lehman,  MuUer,  Munk,  Senator,  und  Zuntz:  Untersuchung  an  zwei  hungernden 

]\Ienschen.     Yirch.  Arch.,  131  Bd.,  Supplement,  1893. 
Luciani:  Das  Hungern  (iibersetzt  von  O.  Frankel),  Leipzig,  1890. 
Lukjanow:  Veriind.  d.  Zellkerne  unt.  d.  Einfl.  d.  Hungerns.     Arch,  des  Sc.  biol.,  vi. 

luid  vii..  1897  u.  1898. 
Meltzer  and  Norris  :  On  the  Influence  of  Fasting  upon  the  Bactericidal  Action  of 

the  Blood.     Jour,  of  Exp.  Medicine,  1899. 
Monti:  Alterat.  del  sist.  nervoso  nell'  inanizione.     Arch.  ital.  de  Biol.,  xxiv.,  1895. 
Miiller:  Stoffwechseluntersuchungen  bei  Krebskranken.     Zeltschr.  f.  klin.  Med.,  xvi., 

1889. 
Miihlmann:  Eussische  Literatur  liber  die  Pathologic  des  Hungerns  (zahlreiche  und 

vielseitige  Untersuchungen).     Centralbl.  f.  allg.  Pathol.,  x.,  1899. 
Munk:  Ueber  die  Folgen  einer  ausreichenden  aber  eiweissarmen  Xahrung.     Yirch. 

Arch.,  132  Bd.,  1893. 
V.  Noorden:  Pathologic  des  Stoffwechsels,  Berlin,  1893. 

Ottolenghi:  Osserv.  sperim.  sul  sangue  asfittico.     Arch.  p.  le  Sc.  Med.,  xvil.,  1893. 
Peri:  Alterations  du  syst.  nerv.  prod,  par  Tinanition.     Arch.  ital.  de  Biol.,  xviii.,  1892. 
Pernice  und  Scagliosi:  Wirkuug  d.  ^Vasserentziehunfr.     Virch.  Arch.,  139  Bd.,  1895 

(Lit.). 
Penzoldt  u.  Fleischer:  Eiufluss  von  Respirationsstorungen.     Virch.  Arch.,  87  Bd., 

1SS2. 
Runge:  Die  Krankheiten  der  ersten  Lebenstage,  Stuttgart,  1893. 
Statkewitsch:  Yeranderungen  d.  Muskeln  u.  Driisen  b.  Hungern.      Archiv  f .  exp. 

Path.,  33  Bd.,  1894. 

§  2.  An  unusual  demand  upon  the  functional  activity  of  an  organ 
for  an  extended  period  of  time  leads  sooner  or  later  to  a  state  of  ex= 


FATIGUE.  7 

haustion,  Avhieli  is,  in  part,  due  lo  tlie  consumption  of  odl -substance, 
and  in  part  to  tbo  formation  of  toxic  i)roducts  of  metabolism,  Avhereby 
the  organ  is  incapacitated  for  furtlier  ♦'xtended  acthity.  INIost  often 
the  results  of  overwork  are  manifested  in  tlie  mnsck's  and  nervous 
system  in  the  form  of  such  symi)toms  as  soi'eness  and  stiffness  of  the 
muscles,  mental  excitement,  sleeplessness,  heavy  feeling  in  the  head,  loss 
of  appetite,  great  -weakness,  nnnatnral  sweating,  and  sometimes  fever. 
Overwork  of  the  heart  leading  to  exhaustion  may  cause  death.  This  may 
occur  either  when  the  heart  is  for  a  short  time  taxed  to  the  extrenui  limit 
of  its  power  or  when  for  a  longer  period  it  works  slightly  under  its 
maximum  capacity.  If  the  exliausted  tissues  are  permitted  to  rest  and 
supplied  with  an  abundance  of  nourishment,  the  loss  of  cell-material 
due  to  the  excessive  activity  will  be  replaced,  the  products  of  metabol- 
ism, which  are  hindering  the  functional  activity  of  the  tissue,  will  be 
i-emoved,  and  the  part  restored  to  its  normal  condition. 

If  a  tissue  is  frecpiently  subjected  to  excessive  functional  demands, 
and  if  the  periods  of  rest  are  too  short  to  admit  of  its  complete  restora- 
tion, there  will  result  ultimately  a  condition  of  permanent  functional  in- 
sufliciency,  a  chronic  exhaustion,  which  may  under  certain  circumstances 
manifest  itself  in  a  degeneration  or  atrophy  of  the  affected  organ.  For 
example,  a  muscle  through  overwork  may  become  atrophic,  and  a  brain 
too  constantly  stimulated  to  activity  without  proper  periods  of  rest  may 
finally  reach  such  a  state  of  weakness  and  exhaustion  that  it  is  incapable 
of  performing  even  its  normal  function.  Through  rest  and  properly- 
regulated  nourishment  such  a  brain  may  recover ;  but  beyond  a  certain 
limit  of  exhaustion  the  functional  insufficiency  may  become  permanent 
and  eventually  manifest  itself  in  anatomical  changes. 

A  very  severe  over-stimulation  of  the  nervous  system,  even  for  a 
very  short  time,  may  under  certain  conditions  lead  to  a  paralysis  of  its 
functions,  which,  in  case  the  heart  and  respiratory  apparatus  are  af- 
fected, may  cause  death,  but  in  the  majority  of  cases  is  of  a  transitory 
nature. 

Overwork  of  any  organ  is  more  quickly  followed  by  fatigue  and 
functional  insufficiency  in  the  case  of  impaired  nutrition.  Fatigue  and 
insufficiency  of  the  heart  are  most  frequently  observed  when  the  general 
nutrition  is  lowered,  as  in  cases  of  fever,  or  when  there  is  deficient  oxy- 
genation of  the  blood,  as  in  poorly  comjDensated  heart  lesions  or  pulmo- 
nary diseases. 

It  is  very  probable  that  overwork  lowers  the  resistance  of  the  body 
to  various  infections. 

When  the  functional  demands  upon  a  muscle  or  gland  are  only  mod- 
erately increased,  and  if  the  nutrition  is  good  and  in  inoportion  to  tlie 
increase  of  labor,  the  affected  tissue  becomes  hypertrophied,  and  is 
thereby  enabled  to  perform  the  increased  work  permanently. 

A  permanent  diminution  or  cessation  of  activity  causes  in  organs 
that  normally  perform  a  definite  and  constant  function  (muscles  and 
glands)  a  loss  of  tissue-substance  (atrophy). 

Literature. 

{OverexeHion  and  Fatigue.) 

Abelous:  Contrib.  A  I'etude  de  la  fatigue.     Arch,  de  Pliys.,  v.,  1893. 

Blake  and  Larrabee  :  Observations  upon  Long-Distancc  llunuers.     Boston  Med.  and 

Siir.ii-.  Jour.,  l<)();j. 


8  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

Bouveret :  La  ncurasthenie,  Paris,  1891. 

Brauns:  Die  Xeurasthenie,  Wiesbaden.  1891. 

Carrieu:  De  1;    latiuue  et  <le  son  influence  patliogenique,  Paris,  1878. 

Edinger:  Neue  Tiieorie  uberdie  Ursaclien  einiger  Nerveukrankljeiteu,  Leipzig,   1894. 

Erb:  Die  zuneiiiiiende  Nervositat  unserer  Zeit,  Heidelberg,  1893. 

De  Fleury:  Pathoiienie  de  I'epuisement  nerveux.     Rev.  de  Med.,  1896. 

Guerrini:  Action  de  la  fatigue  sur  les  cellules  uerveuses.     Arch.  ital.  de  Biol.,  xxxii., 

I8!n». 
Kraepelin:  Zr.r  Ueberburdungsfrage,  Jena,  1897  (Lit.). 

V.  Krafft-Ebing-:  Lehrbuch  der  P.sycliiatrie,  1893;  Gesunde  u.  kranke  JSTerven,  1895. 
Krehl  u.  Romberg-:  Bedeutung  d.  Herzmuskels  u.  d.  Herzganglion.  f.  d.  Herzthatig- 

keit.     Arch.  f.  exp.  Path.,  80  Bd.,  1893. 
Leyden:    Herzkrankheiten  in  Folge  v.  Ueberanstreugung.     Zeitschr.  f.  kliu.  Med., 

xi.,  1886. 
Marfan:  Fatigue  et  surmenage.     Path.  gen.  publ.  par  Bouchard,  i.,  1895. 
Mosso:  Die  Ermudung,  Leipzig,  1893. 
Seitz:  Ueberanstreugung  d.  Herzens.     D.  Arch.  f.  klin.  Med.,  xi.,  1873,  u.  xiii.,  1874 

(Lit.). 
Williams  and  Arnold:  The  Effects  of  Violent  and   Prolonged   Exercise   upon  the 

Heart.     Phil.  Med.  Jour.,  1899. 
Ziehen:  Neurasthenic.     Eulenburg's  Realencyklop.,  xvii.,  1898  (Lit. 1. 

§  3.  High  temperatures  may  act,  either  through  local  destruction  of 
tissue  (hurniny)  or  through  overheutlnf/  of  the  entire  body.  The  latter 
couditiou  is  possible  only  wheu  the  body  is  exposed  to  au  increased  tem- 
perature for  such  a  time  that  it  caimot  protect  itself  from  overheating 
by  increased  heat-dispersion.  In  dry  air  of  from  55-60°  C.  (131-140° 
P. )  the  most  profuse  perspiration  is  no  longer  able  to  protect  the  body 
permanently  from  overheating,  and  in  a  moist  atmosphere  the  same  is 
true  at  even  lower  temperatures. 

If  the  human  body  is  subjected  to  high  temperatures,  it  may  become 
overheated,  and  the  condition  known  as  heat=stroke  may  result.  The 
pulse-rate  is  increased,  the  respiration  very  rapid  and  labored,  the  pupils 
are  dilated,  and  finally  death  may  occur  as  in  the  case  of  the  animals 
made  the  subject  of  experiment.  The  occurrence  of  heat-stroke  is 
favored  by  heavy  bodily  labor,  interference  with  heat-dispersion  through 
impermeable  clothing,  or  by  a  lack  of  water  in  the  body. 

The  direct  action  of  the  rays  of  the  sun  upon  the  head  may  cause 
cerebral  and  meningeal  irritation,  a  condition  characterized  by  hy- 
peremia and  inflammatory  exudations,  and  known  as  sun=stroke  or 
insolation. 

The  local  effects  of  heat  upon  the  skin,  burns,  are,  according  to  the 
intensity  of  the  heat  and  the  time  of  its  duration,  either  hypenemia 
(burn  of  first  degree),  formation  of  a  blister  (second  degree),  tissue- 
eschar  (third  degree),  or  carbonization  ('fourth  degree).  The  heat  pro- 
duces local  changes  in  the  tissues,  and  kills  them  at  a  certain  height  of 
temperature  or  after  a  certain  time  of  exposure  to  its  action. 

When  a  large  part  of  the  surface  of  the  body,  about  one-third,  is 
burned,  the  affected  individual  usually  dies,  even  though  the  burn  is 
only  of  a  slight  degree  and  eschars  are  not  formed.  The  anatomical  find- 
ings in  fatal  cases  of  superficial  burns  w^ould  indicate,  when  death  has 
not  resulted  very  quickly  from  the  severe  shock  to  the  nervous  system 
and  the  overheating  of  the  body,  that  the  cause  of  death  is  to  be  sought 
in  the  changes  in  the  blood  and  in  disturbances  of  the  circulation.  The 
blood-changes  consist  in  the  loss  of  a  portion  of  its  water  and  in  destruc- 
tion of  the  red  blood-cells,  or  in  such  injury  to  them  as  to  diminish  their 
function  and  to  give  rise  at  the  same  time  to  a  deposit  of  the  products  of 
destruction  and  of  haemoglobin  in  the  liver,  spleen,  and  kidneys.     The 


THE    EFFECTS    OF    HIGH    AND    LOW   TEAIPEHATURES.  9 

cLaiiges  are  farther  characterized  by  a  tendency  on  the  pait  of  the  blood 
to  stasis,  hemorrhages,  and  intravascnlar  coaii'ulation,  thi()n<i;h  whicli 
vessels  of  both  the  pnlnionary  and  the  systemic  cii'cnlation  maybe  ob- 
structed, so  that  local  tissne-deii'enerat  ions  and  necros<'S  may  occni-  in  cer- 
tain oroans,  as,  for  example,  in  the  kidneys,  liver,  mncosa.  oi"  the  stomach 
and  intestine,  bones,  and  soft  parts.  It  is  also  ])i()bable  thai  ])oisonons 
products  are  produced  which  liave  an  injurious  action,  i)articularly  ui)ou 
the  uervous  system,  liver,  aud  kidneys. 

Low  temperatures  act  in  the  same  manner  as  high  ones,  in  part 
through  local  injury  and  death  of  tissues,  in  part  through  refrigeration 
of  the  entire  body.  Severe  and  lasting  lowering  of  temperature  causes 
tissue  death ;  after  mild  chilling  there  occur,  as  the  result  of  tissue-de- 
generation, thrombosis,  hyperemia,  and  exudations  which  are  relatively 
rich  in  leucocytes.  A  very  short  refrigeration  at  the  freezing-point  is 
suf&cient  to  produce  degenerative  changes  which  are  quickly  followed  by 
regenerative  proliferation  on  the  part  of  the  cells  remaining  uninjured. 
Epithelial  thickenings  may  be  produced  (Fuerst)  by  repeated  slight  re- 
frigerations (as  well  as  by  repeated  slight  increase  of  temperature). 
The  tips  of  the  extremities,  nose,  and  ears  are  the  most  easily  frozen. 
After  repeated  chillings  of  mild  degree  inflammatory  redness  and  swell- 
ing of  the  skin,  associated  with  severe  itching,  often  occur  {chilblams, 
perniones). 

If  the  temperature  of  the  entire  body  be  markedly  lowered,  a  condi- 
tion of  general  paralysis  results  from  the  diminished  excitability  of  the 
tissues,  the  nervous  system  and  heart  being  especially  affected.  The 
sensorium  becomes  dulled,  the  heart-beat  aud  respiration  gradually  grow 
weaker,  and  finally  cease  entirely.  If  the  body  be  again  warmed,  be- 
fore the  excitability  of  the  tissues  is  wholly  lost,  the  power  of  movement 
in  the  limbs  is  gradually  restored,  and  after  a  time  consciousness  re- 
turns. In  man,  instances  of  complete  recovery  have  been  observed,  even 
after  refrigeration  of  the  body  to  from  24-30°  C.  (75-86°  F,), 

Besides  the  more  severe  forms  of  local  or  general  lowering  of  the  tis- 
sue temj)erature  there  may  occur,  as  harmful  pathogenic  influences,  mild 
general  or  local  chillings,  the  so-called  colds,  as  the  result  of  which  dis- 
ease-phenomena may  manifest  themselves  partly  at  the  seat  of  chilling, 
partly  in  organs  in  distant  parts  of  the  body.  For  example,  after  wide- 
spread refrigeration  of  the  skin  there  may  occur  diarrhoea,  catarrh  of  the 
respiratory  tract,  or  disease  of  the  kidneys;  after  local  chilling  of  the 
skin,  painful  affections  of  the  deep-seated  muscles.  The  exact  relation 
between  these  phenomena  and  the  refrigeration  is  unknown  (the  oft-re- 
peated hypothesis  that  they  are  due  to  hyperemia  of  the  internal  organs 
caused  by  the  chilling  of  the  body-surface  has  not  been  proved),  bnt 
there  is  no  reason  on  this  account  to  deny  the  existence  of  diseases  caused 
by  cold.  Though  many  diseases  foi-merly  attributed  to  "catching  cold  " 
have  been  shown  to  be  of  infectious  origin,  there  yet  remain  a  number 
of  diseased  conditions  for  which  we  know  no  other  etiology  than  that  of 
refrigeration.  Conditions  of  the  body  in  which  the  skin  is  liy])eia'mic 
and  the  perspiratory  function  active  favor  the  taking  of  cold.  Many  in- 
dividuals appear  to  possess  a  X)i'edisposition  on  the  ])arti  of  certain  tissues 
to  the  effects  of  refrigeration ;  in  one  i)erson  certain  muscles,  in  another 
the  mucous  membranes  will  be  affected. 

According  to  the  view  of  many  writers,  refrigeration  of  the  body 
increases  the  susceptibility  to  infection,  so  that,  for  example,  the  patho- 
genic bacteria  which  may  be  present  in  those  cavities  of  the  body  acces- 


10  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

sible  from  without  may,  after  such  refrigeration,  be  able  to  exert  their 
injurious  influeuces  upon  the  tissue. 

If  rabbits  are  placed  in  well-ventilated  incubators  at  a  temperature  of  3&-40°  C. 
(96.5-104°  F.),  their  body  temperature  will  rise  to  39-40^  C.  (102.3-104°  F.),  the  respira- 
tion and  pulse  being  at  the  same  time  greatly  increased  in  frequency.  A  very  marked 
elevation  of  body  temperature  may  lead  in  one  to  three  days  to  death  through  paralysis 
of  the  nervous  and  muscular  systems,  the  chief  symptoms  being  a  marked  increase  of 
both  respiratory  and  cardiac  activity.  If  the  increase  of  body  temperature  is  not  greater 
than  2-3°  C.  (3-5°  F.),  the  animals  may,  if  properly  nourished,  live  from  ten  to  thirty 
days  or  even  longer,  but  they  will  lose  in  weight  and  ultimately  die,  showing  before 
death  a  gradually  increasing  diminution  of  haemoglobin  and  of  red  blood-cells.  De- 
generative changes,  particularly  fatty  degeneration,  occur  in  the  liver,  kidneys,  and 
heart  muscle.     During  the  experiment  there  is  an  increased  production  of  urea. 

The  fact  that  man  dies  so  frequently  after  an  extensive  superficial  burn  of  the  skin 
has  been  explained  in  various  ways.  Billroth,  Fna,  Mendel,  and  others  believed  the 
cause  of  death  to  lie  in  a  suppression  of  the  perspiration  and  the  resulting  accumula- 
tion of  toxic  substances  in  the  blood;  while  others,  as  B.  Sonnenburg  and  Falk.  sought 
the  cause  in  a  reflex  lowering  of  the  vascular  tone.  In  the  foudroyant  cases,  according 
to  Sonnenburg,  the  overheating  of  the  blood  causes  a  paralysis  of  the  heart.  Ponfick, 
Klebs,  von  Lesser,  and  others,  on  the  other  hand,  are  of  the  opinion  that  the  fatal  issue 
is  due  to  injury  and  destruction  of  the  red  blood-cells.  Silbermann,  Welti,  and  Sal- 
violi  also  seek  the  cause  of  death  in  an  injury  to  the  blood,  emphasizing,  however,  not 
so  much  the  destruction  of  the  red  blood-cells  as  the  occurrence  of  stasis  and  coagula- 
tion of  the  blood  in  the  vessels  of  different  organs,  which  are  interpreted  as  resulting 
from  the  changes  in  the  blood.  On  the  other  hand,  Kijanitzin,  Parascandolo,  Sca- 
gliosi,  and  Darn  hold  that  there  is  formed  in  the  bodies  of  burned  individuals  a  poison 
which  has  an  injurious  action  upon  the  nervous  system  and  also  upon  the  liver  and  kid- 
neys. Wilms  seeks  the  cause  of  death  partly  in  a  loss  of  the  water  of  the  body  and 
partly  in  the  absorption  of  poisonous  products  from  the  burned  area. 

According  to  Pfliiger  and  others,  all  the  vital  processes  may  be  brought  to  a  stand- 
still through  refrigeration,  without  its  being  impossible  for  a  recovery  to  take  place 
from  the  apparent  death.  This  may  happen  even  when  the  animal  is  frozen  to  a  solid 
mass.  Preyer  also  holds  the  opinion  that  the  continuity  of  life  may  be  wholly  inter- 
rupted by  refrigeration,  and  designates  subjects  who  are  thus  "lifeless,"  but  still  capa- 
ble of  living,  as  anabiotic.  Frogs  are  said  to  remain  capable  of  life  for  many  hours, 
even  though  the  temperature  be  reduced  to  —2.5°  C.,at  which  temperature  the  heart 
is  frozen.  According  to  the  investigations  of  Koch,  such  anabiosis  of  solidly  frozen 
animals  is  possible  when  only  a  portion  of  the  water  contained  in  the  body  of  the  ani- 
mal is  frozen  and  when  the  thawing  process  takes  place  slowly.  In  the  case  of  rapid 
thawing,  strong  diffusion  currents  are  set  up  between  the  water  coming  from  the  ice- 
crystals  and  the  concentrated  albuminous  solutions  of  the  blood  and  the  tissues;  and 
these  currents  may  exert  a  damaging  effect  upon  the  latter. 

According  to  the  investigations  of  J.  Dewar  (Proc.  of  the  Royal  Soc.,  London,  1900), 
the  seeds  of  wheat,  barley,  mustard,  peas,  and  pumpkins  do  not  lose  their  ger- 
minative  povk'er  when  put  into  liquid  hydrogen;  that  is,  in  a  temjierature  of  —250°. 
Further,  the  protoplasm  imder  these  conditions  was  not  changed  liy  the  cold. 

Not  only  do  the  heat-rays  of  the  sun-light  or  the  arc-light  affect  the  human  body, 
but  their  chemically  active  violet  and  ultraviolet  rays  have  also  an  important 
action  upon  its  tissues.  According  to  Ynung.  Beclanl.  Schnetzler,  Godnew,  and  others 
(for  literature  see  Sack,  I.e.),  the  processes  of  growth  and  regeneration  are  carried 
on  more  rapidly  under  the  influence  of  blue  and  violet  rays  than  under  ordinary  con- 
ditions. According  to  Finsen,  variola-lesions  in  the  skin  run  a  much  more  favorable 
course  when  protected  from  the  violet  rays  by  means  of  red  glass.  According  to  the 
investigations  of  Maklakow  the  violet  and  ultraviolet  rays  of  the  arc-light  can  produce 
a  peculiar  erythema  of  the  skin,  even  when  the  heat-rays  are  excluded  (Widmark). 
Finsen  holds  that  "sunburn"  is  produced  chiefly  by  the  violet  and  ultraviolet  rays. 
Bacteria  in  plate-cultures  are  killed  within  a  short  time  by  exposure  to  the  ultraviolet 
rays  of  the  arc-light.  According  to  the  investigations  of  Godneiv,  Finsen,  M oiler,  and 
others,  the  violet  and  ultraviolet  rays  penetrate  the  skin,  but  are  absorbed  by  the  blood. 
Basing  his  views  upon  these  facts,  Finsen  has  attempted  to  treat  skin  diseases,  espe- 
cially lupus,  cancer,  vascular  nievi,  acne,  etc.,  with  the  ultraviolet  rays  of  the  sun  and 
the  arc-light,  antl  has  been  very  successful  with  the  latter  method.  Fresh  cases  of 
lupus  were  healed  by  it  in  a  relatively  short  time.  The  heat-rays  are  excluded  by  means 
of  the  interposition  of  quartz  lenses  and  chambers  of  running  "water.  A  hollow  lens  of 
quartz  through  which  water  is  flowing  is  pressed  firmly  against  the  affected  area  in 
order  to  exclude  the  blood  which  absorbs  the  ultraviolet  rays.     The  irradiation,  when 


KOEXTGKX    KAYS.  11 

continued  for  about  an  hour,  causes  first  an  inflammation,  leading  after  twelve  hours 
or  more  to  the  fcrmation  of  a  blister.    Later,  scar  tissue  ilevelops  in  the  area  so  treated. 

According  to  investigations  by  Dnyer,  and  confirmed  by  Xcijiser  and  Ilalbcr- 
staedter,  infusoria,  bacteria,  and  animal  tissues  when  impregnated  with  erythrosin 
(solution  of  1:  1,000-1:  4,000)  become  sensitized  to  red  antl  yellow  rays,  .so  that  these 
rays  act  upon  them  in  the  same  manner  as  the  violet  and  ultraviolet.  Since  the  red 
and  )-ellow  rays  possess  a  greater  power  of  penetration  into  the  tissues,  a  more  marked 
and  deejier  effect  of  irradiation  can  be  obtained  by  the  previous  treatment  of  the  tissues 
with  solutions  uf  erythrosin. 

Roentgen-Rays,  acting  upon  the  skin  for  some  time,  cause  in  the  exposed  por- 
tions, ;it  point  of  entrance  and  exit,  degenerative  changes  affecting  chiefly  the  epithelium, 
but  also  tlie  connective-ti.ssue  cells.  These  are  followed  by  inflanunatory  processes. 
Clinically  tliese  changes  show  themselves  usually  about  fourteen  days  after  the  exposure, 
and  reacli  their  acme  after  -some  weeks.  The  hair  and  finger-nails  may  be  lost.  If 
tissue-necrosis  occurs,  the  healing  of  the  resulting  ulcer  is  very  slow  and  diflicult.  The 
Roentgen-rays  have  also  been  used  with  some  success  in  the  treatment  of  lupus  and 
carcinoma  of  the  skin.  Exposures  of  30  to  60  minutes  are  given,  and  repeated  two  or 
three  times.  After  one  or  two  weeks  the  cancer  shows  an  inflammatory  reaction. 
Healing  of  the  neoplasm  takes  place  through  the  destruction  of  the  carcinoma  cells, 
which  are  especially  susceptible  to  the  actioi>  of  the  rays;  and  the  resulting  ulcer  heals 
through  the  formation  of  scar-tissue  and  a  regenc-ition  of  the  epidermis.  In  the  case 
of  carcinoma  of  the  mamma  a  certain  amount  of  destruction  of  the  neoplasm  may  be 
accomplished,  but  not  to  the  extent  of  a  complete  cure.  Recent  cases  have  been 
observed  of  cancer  developing  in  skin  frequently  exuosed  to  Roentgen-rays. 

According  to  investigations  by  Heinekc  and  Warthin,  the  experimental  irradiation 
of  rats,  mice,  guinea-pigs,  rabbits,  and  dogs  causes,  even  after  fifteen-minute  exposures, 
a  marked  destruction  of  the  lymphoid  cells  of  the  spleen,  bone-marrow,  and  lymph- 
nodes.  The  disintegration  of  the  lymphoid  cells  is  evident  almost  inunediatcly  after 
the  exposure,  and  persists  for  some  hours.  After  single  exposures  regeneration  is  rapid, 
but  after  prolonged  or  repeated  exposures  the  spleen  may  finally  become  practically 
devoid  of  lymphoid  cells.  In  exposures  of  this  degree  the  death  of  the  animal  usually 
takes  place  within  ten  days,  after  it  has  exhibited  marked  symptoms  of  intoxication. 
Small  animals  may  be  rendered  blind  l)y  prolonged  exposures.  In  the  use  of  lioentgen- 
rays  as  a  curative  agent  in  leukiemia  it  has  been  shown  that  the  size  of  the  spleen  may- 
be greatly  diminished,  the  white-cell  count  brought  dowTi  to  normal,  the  general  condi- 
tion improved,  and  the  life  of  the  patient  extended  by  one  to  two  years.  Warthin  has 
shown  that  this  improvement  is  due  wholly  to  the  destructive  action  of  the  rays  upon 
the  white  cells  of  the  blood-cell-forming  organs,  and  that  the  essential  disease-process 
is  not  cured.  He  has  also  emphasized  the  dangers  of  an  intoxication  arising  from 
the  products  of  proteid  disintegration,  and  has  shown  the  occurrence  of  extensive 
degeneration  and  calcification  of  the  kidneys  in  cases  so  treated.  His  investigations 
show  also  that  slight  changes  occur  in  the  renal  epithelium  as  the  result  of  short  ex- 
posures. Capps  believes  that  a  leukotoxin  is  produced  in  the  sera  of  animals  exjjosed 
to  the  rays.  Scholz,  Seklin,  Philipp,  Halberstaedter,  and  others  liave  demonstrated 
the  production  of  azoospermia  in  man  and  animals  by  means  of  Roentgen  irradiation. 
Numerous  cases  of  sterility  in  Roentgen-ray  operators  have  been  observed,  liardeen 
found  that  the  death  of  spermatozoa  is  hastened  by  irradiation,  and  that  spermatozoa 
injured  by  short  exposures  to  Roentgen- rays,  but  still  capable  of  fertilization,  may  cause 
the  development  of  monsters  from  ova  fertilized  by  them.  He  concludes  that  nuclear 
materia!  may  be  so  influenced  by  exposures  to  the  rays  that  after  a  latent  period  it  may 
show  marked  abnormalities  in  development.  Foerstcrling  warns  against  tlie  dangers  of 
irradiation  in  young  children.  Edsall  has  reported  an  instance  of  death  following 
Roentgen  irradiation,  and  the  present  tendency  is  to  regard  the  rays  as  agents  capable 
of  producing  serious  damage  to  the  animal  organism. 

BecquereURays  act  similarly  to  the  Roentgen.  Tissue-degenerations  and  in- 
flammations appear  in  the  second  or  third  week  after  the  expo.sure  and  reach  their  acme 
in  20-30  days  (Ilalkin,  I.e.).  Slowly  healing  ulcers  may  be  formed.  Some  success  has 
been  obtained  with  the  rays  in  the  treatment  of  cancer  of  the  skin  and  lupus.  .Accord- 
ing to  Pfeiffer,  Friedhergcr,  and  SrJioltz  tlie  rays  are  bactericidal,  and  a  portion  of  the 
active  rays  can  penetrate  the  tissues  to  a  depth  of  sevend  milhmetres.  lioentgen  and 
Becquerel  rays  are  not,  like  light,  heat,  and  cicetricity,  es|)eeial  forms  of  undulations  of 
the  ether. but  consist  of  extremely  minute  particles  of  matter,  electrons,  which  are  given 
off  into  space  with  great  rapidity.  In  the  case  of  the  Roentgen-rays  the  projecting 
power  is  the  electrical  energy  supplied  to  the  Roentgen  tube.  The  lk'C(pierel  rays 
represent  a  property  of  certain  bodies  designated  Ity  liecquerel  as  radio-artin'l!/.  In 
1896  this  investigator  discovered  that  uranium  and  its  .salts  give  off  rays  that  act  upon 
photographic  plates  in  the  dark  and  are  capable  of  penetrating  bodies  impervious  to 


12  THE    EXTRINSIC    CAUSES    OF    DISEASE, 

light.  In  1898  Madame  Curie  succeeded  in  separating  from  pitchblende  two  radio- 
active bodies  which  were  named  radium  and  polonium.  In  1899  a  third  radio-active 
body  {actinium)  was  discovered  by  Curie  and  Debieme.  Radium  has  been  produced  in 
a  pure  form  and  has  been  the  most  carefully  studied.  It  is  a  new  element,  the  salts  of 
w'hich  are  radio-active  in  the  highest  degree  and  project  electrons  into  space  at  a  velocity 
of  160,000  kilometres  per  second,  :^t  the  same  time  giving  off  heat-rays.  The  air  about 
it  becomes  ionized,  that  is,  becomes  a  conductor  for  electrical  discharges.  The  action 
of  radium  upon  the  tissues  is  similar  to  that  of  Roentgen-rays. 

According  to  Hinstedt  {Ann.  der  Physik,  1903),  numerous  springs,  hot  ones  in 
particular,  are  radio-active,  and  it  is  not  improbable  that  their  special  action  is  in 
part  dependent  upon  this  property. 

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{Effects  of  High  and  Low  Temperatures.') 

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1889. 
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Rep.,  vol.  vii. 
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1901. 
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Wochenschr.,  1889. 
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Ziegler,  xxiv.,  1898. 
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Jacubasch:    Sonnenstich  u.  Hitzschlag,  Wien,  1881. 
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Kijanitzin:    Ursache  d.  Todes  nach  Hautverbrennung.    Virch.  Arch.,  131  Bd.,  1893. 
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Die  Erkaltung.     Arch.  f.  Hyg.,  39  Bd.,  1901. 
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Bd.,  1889. 
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Parascandolo:  Alterat.  du  syst.  nerveuxdans  les  brulures.  Arch,  de  phys.,  x.,  1898. 
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Pictet:    L'l*]mpl()i  des  basses  temper.     Jahresber.  iiber  1893  v.  Hermann,  ii.,  1895. 
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de  Biol..  XV..  1891. 
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radio-activity:  atmospheric  pressure.  13 

Silbermann:    I'lsachen  d.  Todcs  nach  Haiitvorbronminfrcn.     Virch.  Arch.,  119  Bd., 

1S90. 
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allg.  Path..  1890. 
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Ziegler:    Wirkung  erhohter  Eigenwarnie.     Verb.  d.  Congr.  f.  iini.  Med.,  1895. 

{The  IJfcct.s  of  JRadio-actiritif.') 

Apolant:  Wirk.  v.  Radiumstrahlen  auf  die  Karcinom  d.  Miiuse.     D.  med.  Woch.,  1904. 

Bardeen:    The  Action  of  Roentgen  Rays  upon  Spermatozoa.     Anier.  Medicine,  1906. 

Capps:  On  the  Production  of  a  Leukotoxin  by  Roentgen  Irradiation.  Trans.  Assoc, 
of  Anier.  Phys.,  1906. 

Caspari:   Bedeutung  des  Radiums.     Zeitsschr.  d.  diat.  Chir.,  viii.,  1904. 

Edsall:    Dangers  of  Roentgen  Irradiation.     Jour.  Amer.  Med.  As-soc,  1906. 

Fittig:  Behandlung  d.  Karcinome  mit  Roentgenstrahlen.  Beitr.  v.  Bruns,  42  Bd., 
1904. 

Halkin:   Einfluss  der  Becquerelstrahlen  auf  die  Ilaut.    A.  f.  Derm.,  65  Bd.,  190.3  (Lit.). 

Heineke:    Einwirk.  d.  Roentgen-strahlen  auf  inn.  Organe.     Mimch.  med.  Woch.,  1904. 

Perthes:  Einfluss  der  Roentgenstrahlen  auf  das  Karcinom.  Arch.  f.  klin.  Chir., 
71  Bd.,  1903. 

Scholtz:  Einfluss  der  Roentgenstrahlen  auf  die  Haut.  Arch.  f.  Derm.,  59  Bd.,  1902; 
Roent2;enstrahlen.  Eulenburg's  Jahrb.,  ii.,  1904;  Wirk.  d.  Radiums.  D.  med. 
Woch.,  1904. 

Warthin:  The  Effects  of  Roentgen  Rays  upon  the  Blood-fonning  Organs.  Inter- 
national Clinics,  Jan.,  1906;  ibid.  With  Especial  Reference  to  the  Treatment  of 
Leukemia.  Physician  and  Surgeon,  1907  (Lit.);  Action  of  Roentgen  Rays  upon 
the  Kidney.     Am.  Jour,  of  Med.  Sciences,  1907  (Lit.). 

Weber:  Die  heutige  Kenntnis  d.  Radioaktivitat.     D.  med.  Woch.,  1904. 

§  4.  A  sudden  lowering  of  atmospheric  pressure,  as  in  tlie  ease  of 
monntain-climbiug  and  balloon  ascents,  may  canse  conditions  of  great 
exhaustion,  with  marked  palpitation  of  the  heart,  nnconsciousness,  ir- 
regular breathing,  and  sometimes  vomiting,  and  bleeding  from  the  gums 
and  lips.  These  symptoms  depend  essentially  upon  a  Jack  of  oxygen 
(P.  Bert),  the  capillaries  of  the  lungs  being  unable  to  take  up  sufficient 
oxygen  from  the  highly  rarefied  air.  Kronecker  believes  that  they  are 
to  be  referred  to  disturbances  of  the  pulmonary  circulation.  According 
to  the  investigations  of  Schumburg  and  Zuntz,  it  appears  that  a  given 
amount  of  labor  calls  for  a  greater  amount  of  oxygen  at  an  increased  ele- 
vation than  at  a  lower  level.  The  symptoms  of  mountain -sickiioss  appear 
at  a  loAver  elevation  than  those  of  balloon-sickness,  owing  t(»  the  demands 
made  upon  the  muscles  in  the  former  case  during  the  climbing.  Duiing 
the  building  of  the  Gorner  Grat  Eailway  it  was  found  tliat  at  a  lieight 
of  2,700-3,000  metres  the  capacity  of  the  laborers  was  diminished  to  a 
third. 

According  to  the  researches  of  Egger,  Miescher,  and  others,  a  sojourn 
in  high  altitudes  leads,  after  a  short  time,  to  an  increase  in  the  number 
of  red  cells  and  a  greater  hiemogh (bin-content  of  the  blood. 

Schaumann  and  Kosenquist  hold  that  the  same  i)henomenon  maybe 
observed  in  animals  confined  for  some  tinu;  in  bell-jars  at  a  lower  atmos- 
pheric pressure.  Other  authors  (Schumbui-g,  Zuntz,  Goltslein)  oppo.se 
this  view,  and  maintain  that  the  ])henomenon  is  due  either  to  a  thicken- 
ing of  the  blood  from  loss  of  water  and  to  changes  in  the  distribution  of 
the  blood,  or  to  changes  in  volume  of  the  measuring-a])paratus;  they 
endeavor  to  exi^laiu  the  favorable  effects  which  many  individuals  expe- 


14 


THE    EXTRINSIC    CAUSES    OF   DISEASE. 


If- 


rience  from  a  residence  at  high  altitudes  by  certain  stimnlating  iuflu- 
ences  (greater  exi)osure  to  sun's  rays)  which  affect  the  nervous  system 
and  cause  increased  metabolism.  According  to  Marti,  intense  and  pro- 
Jonged  irradiation  of  the  body  stimulates  the  formation  of  red  blood-cells 
and  to  a  lesser  degree  also  that  of  the  haemoglobin. 

A  sojourn  in  diving-bells  or  caissons,  such  as  are  employed  in  build- 
ing operations  beneath  the  water,  in  which  the  atmospheric  pressure  is 
increased,  under  certain  conditions,  as  high  as  four  atmospheres  or  even 
greater,  causes  a  slight  difficulty  in  breathing  and  a  relatively  unimpor- 
tant increase  of  the  pulse-rate.  If  a  change  he  made  quickly  from  the 
compressed  atmosj)here  to  air  of  ordinary  pressure,  there  may  occur 
within  an  hour  a  condition  of  great  fatigue,  tightness  of  the  chest,  ring- 
ing of  the  ears,  cramps  in  the  muscles,  pains  in  the  joints  and  limbs, 
haemorrhages  from  the  nose,  ears,  and  lungs,  dilatation  of  the  pupils,  and 
under  certain  conditions  paralysis,  coma,  delirium,  and  even  death  after 
an  interval  of  from  one  to  twenty  days.     The  cause  of  these  phenomena 

is  probably  to  be  found  in  the  obstruc- 
tion of'  blood-vessels  of  the  spinal  cord 
by  bubbles  of  nitrogen  that  has  been  ab- 
sorbed under  the  high  pressure  (Hoche). 
According  to  exjDerimental  investiga- 
tions of  Heller,  Mager,  and  von  Schrot- 
ter,  the  blood,  after  rapid  removal  of 
pressure,  contains  free  gas  (almost  ex- 
clusively nitrogen),  so  that  free  gas 
circulates  in  the  blood.  In  fatal  cases 
associated  with  paralysis  areas  of  de- 
generation (Nikiforoff)  are  found  in 
the  white  columns  of  the  spinal  cord, 
in  which  individual  nerve-fibres  present 
marked  changes  in  the  form  of  swelling 
of  the  axis  cylinders,  and  disintegration 
of  the  medullary  sheaths,  with  the  for- 
mation of  vacuoles  in  the  place  of  the 
nerve-fibres  that  have  been  completely 
destroyed.  If  the  gray  matter  is  in- 
volved, the  ganglion-cells  may  also  de- 
generate. 

Changes  in  the  electrical  condition 
of  the  atmosphere  and  in  the  magnetic 
state  of  the  earth  have  no  demonstrable  influence  upon  the  human 
body ;  on  the  other  hand,  electric  discharges,  as  lightning-stroke,  may 
cause,  in  part,  local  lesions  of  the  skin  resembling  burns  (Fig.  1),  hajm- 
orrhages  in  the  skin,  and  burning  of  the  hair,  and,  in  part,  lesions  of  the 
whole  body.  Under  certain  circumstances  lightning-stroke  causes  lacera- 
tion of  internal  organs,  as,  for  examj^le,  of  the  heart  and  liver.  The 
most  frequent  and  important  effect  of  lightning-stroke  is  a  paralysis  of 
the  nervous  system,  which  gives  rise  to  a  severe  dyspnoea,  which  may 
be  fatal  immediately  or  after  a  few  minutes  or  hours,  or  may  gradually 
I)ass  away  after  several  hours,  days,  or  weeks.  Only  rarely  do  individual 
nerve-trunks  remain  permanently  paralyzed.  A  transitory  paralysis 
may  occur  when  the  electrical  discharge  has  not  passed  through  the  bo(l>, 
but  has  descended  in  its  neighborhood. 

In  individuals  who  have  been  struck  by  lightning  there  may  be  found  ] 


Fio.  1.— Ligbtning-flgures  on  the  shoul- 
der, breast  and  arm  of  a  woman  struck  by 
ligbtning. 


ELECTRIC    Cl'RREXTS.  15 

slight  or  severe  burns  of  the  skin  corresponding  to  the  points  ol"  imiI ranee 
and  exit  of  the  current,  and  various  injuries  to  the  tissues  in  the  course 
of  its  path  thiough the  body.  The  marks  of  the  bui'u  are  for  the  greater 
part  red,  and  form  peculiar  branching  zigzag  lines,  the  so-called  Ht/htninff 
Jiffiires  (Fig.  1),  which  are  essentially  a  hypenvmia,  and  soon  disapi)ear 
if  the  burns  are  not  severe. 

The  passage  of  powerful  electric  currents  of  high  tension,  such  as 
are  generated  by  dynanu)s,  thiough  the  human  body,  as  nuiy  liai)i)en 
Mhen  ail  individual  is  placed  in  a  circuit  or  comes  into  contact  with  an 
uninsulated  conductor,  may  give  rise  to  severe  disturbances  or  cause 
death.  According  to  Kratter,  the  lower  limit  of  danger  occurs  at  a  ten- 
sion of  about  five  hundred  volts.  Alternating  currents  are  much  more 
dangerous  than  continuous  ones  of  the  same  strength  and  tension.  When 
the  effects  are  uot  fatal,  the  injured  persou  is  suddenly  rendered  uncon- 
scious, this  condition  lasting  for  a  few  minutes  or  several  hours,  and  for 
several  days  afterward  symptoms  of  vertigo,  prostration,  headache,  and 
palpitation  of  the  heart  may  persist  (Kratter).  At  the  points  of  contact 
more  or  less  severe  burns  are  produced. 

lu  fatal  cases,  death  takes  place  suddenly  or  rarely  after  teu  or  thirty 
minutes.  The  autopsy  findings,  aside  from  the  burns  at  the  points  of 
contact,  are  evidences  of  suffocation  and  hyperveuosity  of  the  blood, 
stasis  of  the  blood  within  the  thoracic  vessels,  and  often  small  scattered 
haemorrhages  which  are  due  partly  to  the  direct  action  of  the  current. 
The  cause  of  death  is  paralysis  of  the  centre  governing  the  respiration 
or  the  heart's  action. 

Literature. 

(Effects  of  Changes  of  Atmosplieric  Fressure  and  of  Solarization.) 

Bert,  P. :  La  pression  barometriqne,  Paris,  1878.  Trr-    i,  j 

Egg-er-  Verauderunffen  d.  Blutes  im  Hoch sebirge.     Congr.  f.  inn.  Med.,  Wiesbaden, 

1893;  u.  Arch,  f.'exp.  Path.,  39  Bd.,  1897.  .  „      -r.    ,       • 

Gottstein:   Klimat.  Einfliisse  als  Krankheitsursachen.     Ergebn.  d.  allg.  Path.,  iv., 

Wiesbaden,  1899;  Vermehrung  der  rothen  Blutkorp.  im  Hochgebirge.      Munch. 

nied.  Woch.,  1899.  ^,.     ^     ,      .^^^    ,.  , 

Heller,  Mag-er,  Schrotter:  Mitth.  liber  Caissonarbeiter.     Khn.  Woch.,  1895;  Unter- 

siifli.  lilx-r  d.  Wirkung  rascher  Veranderungen  d.  Luftdruckes.     Pfluger's  Arch., 

(17  Bd.,  1897;  Luftdruckerkrankungen,  Wieii,  1900. 
Hoche:  Luftdruckerkrankung  d.   Centralnervensystems.     Berl.    khn.    Wochenschr., 

1S97. 
Kronecker:     Die  Bergkrankheit.     Deutsche  Klinik,  Bd.  xi.,  1903. 
Leyden-  Durch  plotzl.  Verminderung  d.  Baroraeterdrucks  entsteh.  Ruckenmarksattec- 

tion.     Arch.  f.   Psych.,  ix.,  1879.  ^     ^      ^^^^ 

Loewy  u.  Zunz :  Eiutiuss  d.  verdunnt.  Luft.     Pfluger's  Arch.,  189 <.  _ 
Marti:  Wirkung  der  Hautreize  und  Belichtung.     Verh.  d.  Congr.  f.  inn.  Med.,  Wies- 
baden, 1897.  .     ^^^^ 
Mercier:  L'lnfluencedel'altitude.     Arch,  de  phj^s.,  vi.,  1894. 
Miescher:  Bezieh.  zwisch.  Meereshohe  u.  Beschaftenh.  d.  Blutes.     Corrbl.  f.  schweiz. 

Aerzte,  1893. 
Mosso:  Der  Menschauf  den  Hochalpen,  Leipzig,  1899.  ,,       „      ^    .  a 

Nikiforofif:    Veriinderungen   d.  Kuckenmarks  in   Folge  schneller  Ilerabsetzung  des 

l.aromctrischen  Druckes.     Beitr.  v.  Ziegler,  xii.,  1892. 
Schaumann  u.   Rosenqvist:  Blutveriind.   im  HOheukhma.     Zeit.   f.  klin.   Med.,  ^o 

Schumburg  uiul  Zunz :  Einwirkung  des  Ilochgebirges.  Pfluger's  Arch.,  63  Bd.,  1896. 
Snell:  Compressed-Air  Illness,  London,  1890. 

Wolff-  Einfluss  des  Gebirgsklinias  auf  d.  ]\Ienschen,  Wiesbaden,  1890. 
Zunz:  Pathogenese  der  durch  Luitdrucksauderuugeu  erz.  Krankheitcn.     lortschr.  d. 
Med..  XV.,  1897. 


16  THE    EXTRINSIC    CAUSES    OF    DISEASE. 


{Effects  of  Lightning  and  of  Electrwal  Currents. ) 

D'AXBonval:  L'enerffie  electrique.     Path.  gen.  publ.  par  Bouchard,  i.,  Paris,  1895. 

Dinner:  Ueber  die  Wirkimg  des  Blitzes.     In. -Diss.,  Leipzig,  1865. 

Ebertz:  Ueber  Blitzverletzungeu.     In. -Diss.,  Tubingen,  1892. 

Freund:  Wirkung  der  Polentladung   hochgespannter   Induktionsstrome.     Akad.    d. 

Wiss.,  Bd.  cix.,  1900. 
Jellinek:  Verand.  im  Nervensystem  durch  Blitz  u.  Starkstrome.      Virch.   Arch.,   170 

]]d.,  1902;  Elektropathologie,  Stuttgart,  1904 
Kratter:   Wirkung  d.  Blitzes.     Vierteljahrsschr.  f.  ger.  Med.,  1891;  Tod  durch  Elek- 

tricitat,  Wien,    1896  (Lit.);  Elektrische   Verungluckungen.     Eulenb.  Jahrb.,    vi., 

1896  (Lit.). 
Liman:  Blitzsehlag.     Deutsch.  med.  Wochenschr.,  1885. 
Mills  and  WeisenTburg:     The  Effects  on  the  Nervous  System  of  Electric  Currents  of 

High  Potential.     Univ.  of  Penn.  Med.  Bull.,  1903. 
Prevost  et  Battelli:  La  niort  par  ies  decharges  electriques.     J.  de  phys.,  i.,  1899. 
Vincent:  Contrib.  a  I'hist.  medicale  de  la  foudre,  Paris,  1875. 

2.    The  Origin  of  Disease  through  Mechanical  Influences. 
§  5.  Traumatic  influences  of  various  kinds  leadiug  to  concussion, 

bruising,  and  laceration  of  tissue  are  of  very  frequent  occurrence,  and 
act  partly  through  the  tearing  and  destruction  of  tissue,  partly  through 
changes  in  tissue-organization  not  recognizable  to  the  naked  eye,  and 
partly  through  lesions  and  ruptures  of  the  blood-  and  lymph -vessels,  and 
through  irritation  and  paralysis  of  nerves.  The  sequelae  are  partly 
necrosis  and  destruction  of  tissue,  partly  disturbances  of  circulation,  inflam- 
mation, and  regenerative  proliferations.  Frequently  repeated  mechanical 
traumatisms  of  slight  degree,  such  as  rubbing,  may  give  rise  to  congestive 
hi/percemia  and  inflammations,  which  may  lead  further  to  hyperplastic 
growths  of  tissue.  If  large  quantities  of  insoluble  dust  particles  are  con- 
tinuously taken  into  the  lungs  indurations  of  the  pulmonary  tissue  may 
develop  in  consequence.  As  a  result  of  prolonged  j>/y'.s%s»/-e  and  dimimition 
of  space,  atrophy  of  an  organ  or  tissue  may  occur  (corset-liver). 

After  a  single  or  after  frequently  repeated  trauma,  there  may  de- 
velop under  certain  conditions  at  present  unknown  to  us,  malignant  new- 
formations  of  tissue  called  tumors.  Trauma  may  further  pave  the  way 
for  an  infection,  either  in  that  the  wound  caused  by  the  trauma  is  in- 
fected at  the  time  of  injury  or  is  secondarily  infected  from  iviihout ;  or  that 
7nicro-organisms  were  previously  present  in  the  body  under  couditions  in- 
hibiting their  growth,  and  these  find  in  the  injured  tissues  a  suitable  soil  for 
growth,  so  that  to  the  trauma  an  infection  is  joined. 

Traumatic  influences  affect,  first  of  all,  the  external  parts  of 
the  body;  but  it  may  happen,  either  with  or  without  visible  injury 
to  external  parts,  that  internal  organs  may  be  injured,  and  the 
internal  lacerations,  necroses,  and  hicmorrliages  thus  produced,  may 
be  followed,  not  only  by  inflammations  and  reparative  tissue  pro- 
liferations,  but  also  by   malignant  neoplasms,  and  by  infective  proc- 


Mechanical  lesions  (also  thermal,  electrical,  and  corrosive)  run  a  spe- 
cial course,  if  through  the  local  injury  the  nervous  system  becomes  in- 
volved. Such  involvement  occurs  either  through  the  direct  action  of 
the  trauma  upon  the  central  nervous  system ;  or,  by  the  stimulation  of 
the  sensory  or  sympathetic  nerves,  the  central  nervous  system  may  be 
so  affected  that  a  number  of  additional  nervous  symptoms  follow. 

If  the  direct  concussion  of  the  cranium  is  followed  by  paralysis  of 
the  cerebral  function  and  unconsciousness,  the  condition  is  termed 
commotio  cerebri  or  cerebral  concussion.     This  term  is  especially  used 


shock:  TKAT-MATIC   xkii^osks.  17 

when  the  ti-auuia  lias  pi-oduciHl  no  visible  changes  in  I  he  stinclnrc  of  the 
brain,  or  at  least  none  of  any  size  oi-  importance. 

Excessi\e  stimulation  of  the  peripheral  nerves  may  cause  ;i  rellex  in- 
hibition or  i)aralysis,  involvini;  chielly  the  functions  of  the  heart  and 
resi)iratory  apparatus;  the  symptoms  thus  i)roduce(l  b<nn<;  collectively 
designated  as  shock.  The  uiost  freiiuent  causes  of  shock  are  injuries  to 
the  spinal  column,  abdominal  cavity,  and  scrotum,  less  frequently  to 
the  extremities  and  thorax.  Further,  shock  may  be  cansed  by  light- 
ninu-stroke,  burns,  corrosions  of  the  skin,  feai-,  and  ])sychical  ennttions 
through  Avhatever  avenue  of  i)erce])tion  they  may  be  called  forth.  In- 
dividuals whose  nervous  systems  are  in  a  certain  condition  of  excitement 
are  especially  liable  to  shock;  conditions  of  narcosis  and  drunkenness 
inhibit  its  occurreuce. 

Shock  is  characterized  chiefly  by  weakened  energy  on  the  i)art  of  the 
heart  and  irregular  breathing,  which  lead  to  a  decrease  in  the  inter- 
change of  gases  iu  the  tissues  and  to  a  lowering  of  the  temperatni-e 
(Eoger).  The  consciousness  is  usually  preserved,  the  skin  and  visible 
mucous  membranes  are  pale,  the  pulse  is  snuill  and  markedly  quickened, 
often  iri'egular  and  intermittent. 

Further,  the  individual  suffering  from  shock  may  be  either  excited, 
groan,  shriek,  aud  complain  of  a  fearful  anxiety  associated  with  dys])n«a 
(erethistic  shod-);  or  he  may  liecpiiet,  with  sunken  couutenance,  and  ex- 
hibit evidences  of  great  weakness  of  both  sensory  and  motor  functions 
(torpid  sJiorl).  Iu  severe  cases  death  takes  place  from  the  stoppage  of 
the  heart  and  cessation  of  respiration. 

Shock,  in  being  due  to  the  over-stimulation  of  the  peripheral  nerves, 
is  closely  allied  etiologically  to  the  phenomenon  known  as  syncope  ;  but 
the  last-named  condition  differs  essentially  from  shock  iu  that  its  chief 
symptom  is  a  transitory  loss  of  consciousness,  while  the  functions  of  the 
heart  and  respiration  show  no  marked  disturbance.  Syncope  is,  further, 
usually  preceded  by  prodromal  symptoms,  such  as  dizziness,  ringing  iu 
the  ear,  and  darkening  of  the  visual  field,  these  being  absent  in  shock. 

Xot  infrequently,  following  an  injury  to  some  part  of  the  body,  there 
may  arise  a  more  or  less  pronounced  functional  disturbance  of  the  ner- 
vous system,  which  may  often  persist  long  after  the  local  injury  has 
healed,  so  that  such  disturbance  is  in  no  way  dependent  upon  anatomical 
changes  in  the  peripheral  or  central  nervous  system,  but  must  be  re- 
garded as  ^ inirdtj  functional  distnrhdncr  of  ]>s)/c]ticat  orif/in.  Such  condi- 
tions are  termed  traumatic  neuroses  or  accident  nervous  diseases,  and 
are  characterized  chietiy  by  subjective  but  in  part  also  by  object  i\e  symp- 
toms. To  the  first  belong  especially  i)aius  not  definitely  localized  at 
the  seat  of  injury,  as  headache,  ])ain  in  the  ch(\st,  backache,  dillicnlty 
iu  movement,  geneial  lassitude,  inability  to  ])eil'orni  mental  iaboi-,  dnl- 
ness  of  ])erceptiou,  disturbances  of  sight.  Hashes  before;  the  eyes,  dizzi- 
ness, lestless  sleep,  loss  of  aj^petite,  and  disturbances  of  digestion.  AN'ith 
these  last  symptoms  are  associated  ])sycliical  dei»ression  of  a  hyi)ochon- 
driacal  or  melancholic  chai-acter,  irregularly  placed  areas  of  cutaneous 
ana'sthesia,  enfeeblement  of  the  senses  of  taste,  hearing,  and  smell,  motor 
paralysis,  cramps,  and  hypei-u'sthesia,  concentiic  narrowing  of  the  \  isnal 
field,  ])areses,  muscular  spasms,  tremors,  acceleration  of  iIk-  pulse,  and 
tendency  to  sweating. 

xVll  of  these  i)henomena  depend  ess<'ntially  upon  a  ps\ cliic  al  sliatter- 
ing  of  tlx' ])eicei)tlve  life,  a  psychoneurosis  wliich  is  less  dl'ten  (hie  l(» 
the  ti'annia  and  llie  associateil  i)sychical  shock  than  to  the  resulting  anxi- 


18  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

ety  over  liealtli  and  business  matters.  The  condition  in  part  partakes 
of  tlie  nature  of  hysteria,  as  characterized  by  a  disturbance  of  the  normal 
relation  between  the  mental  and  bodily  processes ;  in  part  of  hijpochon- 
dria,  as  recognized  by  the  spontaneous  occurrence  of  abnormal  sensa-| 
tions;  and  in  part  of  a  neurasihenia,  which  reveals  itself  by  tlie  produc-j 
tion  of  abnormal  pathological  sensations  through  relatively  slight 
stimulation  or  exertion.  If  the  will  no  longer  controls  the  motor  centres,  .| 
hysterical  paralyses  arise ;  if  the  normal  control  and  inhibition  of  thej 
will  are  lost,  so  that  unreasonable  will-stimuli  are  created  and  influence! 
the  muscles,  hysterical  twitchings,  contractures,  or  convulsions  take  place. 
If  a  nervous  stimulus  arising  in  the  sensory  tract  fails  to  reach  the  con- 
sciousness, there  follows  a  hysterical  anaesthesia;  if  there  arise  in  the! 
consciousness  the  images  of  expected  or  feared  sensations,  and  if  these; 
images  are  intensified  into  actual  subjective  stimuli  of  consciousness, 
hysterical  pains  and  neuralgias  result  (Striimpell). 

Bosenbach  designates  as  kinetoses  those  diseases  which  arise  when  energetic  anri 
continuous  movements  of  the  body  in  one  direction  are  changed  into  the  opposite  direc 
tion,  so  tliat  a  shifting  of  the  internal  organs  results.  In  this  class  belong  the  patho 
logical  phenomena  observed  in  seasickness,  and  in  the  conditions  caused  by  see-sawing.' 
wJiirliiui,  movemen  t  in  a,  vertical  direction,  and  sudden  stoppage  of  motion.  As  a  result  o1| 
the  rapid  change  in  direction  of  bodily  motion,  the  molecules  which  are  moving  in  th<: 
line  of  the  primary  direction  are  forced  to  move  in  the  opposite  direction;  and,  ac 
cording  to  Rosenbach,  such  a  change  is  sufHcieut  to  cause  more  or  less  important  molec 
ular  disturbance.  He  explains  the  S3-mptoms  of  seasickness,  as,  for  example,  the  ab 
normal  secretion  of  the  stomach,  the  increase  of  intestinal  peristalsis,  the  vomiting,  etc. 
as  the  residts  of  purely  mechanical  influences  on  the  tissues,  and  believes  that  thi 
liver,  intestine,  brain,  and  nerve-plexuses  are  similarly  affected  through  mechanical  in 
fluences  acting  upon  their  protoplasm.  On  the  other  hand,  Bim  refers  seasickness  t( 
an  acute  anaemia  of  the  brain  which  causes  the  nausea  and  vomiting.  A  horizonta 
position  and  the  administration  of  a  water  solution  of  chloral  hydrate,  which  dilate 
the  arteries  of  the  head,  have  a  favorable  action  upon  the  condition. 

Literature. 

{Effects  of  Trauma.) 

Binz:    Ueber  die  Seekrankheit.     Ceutralbl.  f.  inn.  Med.,  1903. 

Bruns:    Uufallsneurosen.     Eulenburg's  Jahrb.,  viii.,  1898  (Lit.). 

Fischer:    Ueber  den  Shock.     Saminl.  klin.  Vortr.  v.  Volkmann,  No.  10,  1870. 

Freund:    Traumatische  Neurosen.     Samml.  klin.  Vortr.,  No.  51,  Leipzig,  1892. 

Groeningen :  Ueber  den  Shock,  Wiesbaden,  1885. 

Hober:  tshock  durch  Reizung  seroser  Haute.     Arch.  f.  exp.  Path.,  40  Bd.,  1897. 

Jolly:  Traumatische  Epilepsie.     Char. -Ann.,  xx.,  1895. 

Lejars:  Les  agents  mecaniques.     Path.  gen.  publ.  par  Bouchard,  i.,  1895. 

Oppenheim:  Die  traumatischen  Neurosen,  Berlin,  1892. 

Rog-er:  Choc  nerveux.     Arch,  de  phys.,  v.,  1893,  vi.,  1894. 

Rosenbach.:    Die  Seekrankheit,    Wieu,    1896;    u.  Euleuburg's  Realeucyklop.,   xxii 

1899. 
Sachs  u.  Freund:  Die  Erkranknngen  des  Nervensystems  nach  Unfalleu,  Berlin,  189' 
Seeligmiiller :  Unfallnervenkrankheiten.     Encyklop.  Jahrb.  der  ges.  Heilkunde,  181 

(Lit.). 
Stern:  Die  traumatische  Entstehung  innerer  Krankheiten,  Jena,  1900  (Lit.). 
Striimpell:  Traumat.  Neurosen.     Munch,  med.  Woch.,  1889;  Verh.  d.  XII.  Congr.  ' 

inn.  Med.,  1893. 

3.   The  Origin  of  Disease  through  Intoxication. 

§  6.  By  poisoning  or  intoxication  is  meant  that  impairment  ofheaUi\ 
caused  hy  the  injury  to  a,  tissue,  which  certain  substances,  by  virtue  of  the\ 
chemical  tiature,  are  able  to  produce  under  certaiyi  conditions.     Such  sul 


POISOXS.  10 

tanoes  aro  termed  poisons,  and  are  derived  i)artly  fiom  tlie  mineral 
jkinjixlom,  partly  from  the  vegetable,  and  jjaitly  Croni  tiie  animal  kinj,^- 
|dom.  They  may  occur  in  a  natnial  slate  oi-  Ihey  may  be  i)r()dnced 
jartiticially  from  inorganic  or  organic  suhslances.  Many  of  tiie  most 
[important  poisons  are  products  of  either  jdant  or  animal  life,  and  are 
iformed  either  within  the  tissues  of  tlie  i>lant  or  animal,  or  from  their 
ifood-sui)ply  by  the  transformation  of  substances  which  are  either  inert 
for  possess  an  entirely  ditfeient  action. 

The  most  imjHtrtinit  poisons  hflo)if/inf/  to  tlir  miurval  I'nxjdoni  or  ir/iich  arc 
produced  from  miucnds  an' :  metallic  nu'icuiy,  chloiine,  bromine,  iodine, 
sulphur,  and  various  cond>inations  of  these  substances,  ditfeient  combi- 
nations of  arsenic,  antimony,  lead,  barium,  iron,  coppei-,  silver,  zinc, 
[potassium,  sodium,  chiomium,  etc.  Of  the  poisons  containing  carbon, 
which  are  artifieialli/  produced,  the  most  important  are:  chloroform, 
chloral  hydrate,  ether,  alcohol,  iodoform,  carbon  bisulphide,  hydro- 
cyanic acid,  potassium  cyanide,  oxalic  acid,  nitroglycerin,  amyl  nitrite, 
ipetroleum,  carbolic  acid,  nitrobenzole,  i)icric  acid,  and  aniline.  It  may 
|be  observed  in  this  couuection  that  modern  chemistry  is  constantly  pro- 
iducing  new  substances,  some  of  which  are  poisons. 

I  Of  the  poisons  produced  hji  ptlants  of  the  higher  order,  those  of  chief  im- 
Iportanceare:  the  vegetable  alkaloids,  such  as  morphine,  cpiinine,  colchicine, 
[atropine,  hyoscyamiue,  veratrine,  strychnine,  curariue,  solanine,  nico- 
[tine,  digitaline,  santonin,  aconitiue,  cocaine,  coniine,  muscarine,  and 
|ergotiue,  all  of  which  in  relatively  small  doses  may  cause  poisoning. 
I  The  lower  forms  of  plant  life,  especially  bacteria,  produce  an  extraordi- 
[nary  variety  of  both  j^oisonous  and  non-poisonous  substances,  out  of  the  food 
material  in  irhirh  they  develop.  Some  of  these  substances  are  similai-  to 
(the  vegetable  alkaloids,  others  to  the  ferments,  and  are  therefoi-e  desig- 
nated toxic  cadaveric  alkaloids,  toxic  ptoma'ins.  toxins,  and  toxenzymes  (com- 
pare §  11).  It  may  happen  that  the  l)lood,  tlesh,  or  any  organ  of  a 
healthy  animal  may  accpiire  poisonous  properties  thi-ough  the  presence 
liii  it  of  poisonous  products  of  bacterial  growth.  8uch  diseases  due  to 
'bacterial  poisons  in  the  food  are  known  as  botulism  us,  sausage,  meat,  fish, 
[and  cheese  poisoning.  These  conditions  are  to  be  explained,  in  i)art,  by 
the  growth  of  bacteria  (B.  botulinus)  in  the  food-stuff  and  the  f(nination 
of  poisonous  ])roducts,  true  toxins  (i^  11  );  in  ])art  by  the  fact  that  geiius 
were  present  in  the  tissues  of  the  animal  befoi-e  death,  the  animal  being 
slaughtered  while  diseased,  and  the  nse  of  its  liesh  as  food  causes  either 
poisoning  or  the  same  disease  as  that  affecting  the  animal.  I'nder  cer- 
tain conditions  foods  which  are  not  spoiled  may  already  contain  bacteria, 
and  these  may  develo])  in  the  intestine  of  the  individual  eating  the  food 
and  cause  ])oisoning  tlii'ough  tlu'  production  of  toxins,  or  enzymes. 

Acc<u'ding  to  Lombroso,  the  disease  pdlagnt,  A\hich  is  of  common 
occurrence  in  Italy,  Koumania,  and  (Jicect',  is  caused  by  the  eating  «»f 
decomposed  coin.  The  disease  l:<il:l:e  oi-  heri-beri,  wliich  is  euih'mie  in 
Tapan,  is  regarded  by  Mima  and  Vanuigiva  as  due  t(>  the  extended  use 
of  rice  whicli  has  been  spoiled  in  drying. 

AmoWfi  the  a ni)nals  which  normally  produrr  poisons  irilhin  crrlain  lissiits 
of  their  bodies,  the  best  knoMU  are:  serpents,  toads,  salamanders,  tisli, 
mussels,  oysters,  scorpions,  Spanish  flies,  and  many  stinging  insects. 

Certain  forms  of  sea-fish  are  poisonous  at  ail  tiinos.  others  only  at  certain  periods, 
and  observ^ations  have  been  made  particularly  of  such  fish  found  in  Jai)anese  waters. 
According   to  Saotnchenko,  the  poison  of  m-niy  jjoisonous  fishes  is  secreted  bv  certain 


20  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

skin-glands  found  at  the  roots  of  the  dorsal  and  caudal  fins,  and  maybe  found  also  in  the 
eggs  of  such  fish.  According  to  Remy,  Miura,  and  Takesaki,  the  poison  is  secreted 
in  the  sexual  glands  alone  in  the  case  of  the  poisonous  fish  belonging  to  the  family 
Gymnodontes  (tetrodons).  According  to  Mosso,  there  is  found  in  the  blood-serum  of 
eels  a  toxic  substance  (ichthytoxin)  which,  when  introduced  into  the  small  intestine 
of  animals  experimentally,  causes  symptoms  of  poisoning  and  may  kill  the  animal. 


.\ccording  to  M.  Wolff,  the  liver  of  mussels  {Mytilus  edulis)  contains  the  poison;  its 
action,  according  to  Schmultmann,  Virchoiv.  Salkowski,  and  Brieger,  is  similar  to  that 
of  curare.  BrUger  has  also  shown  that  from  the  poisonous  mussels  there  can  be  ob- 
tained basic  sulistances  closely  related  to  ptomains.  the  basic  products  of  decomposi- 
tion. To  what  extent  the  causes  of  the  production  of  poisons  in  poisonous  fishes  and 
moUusks  are  to  be  ascribed  to  normal  and  to  what  e.xtent  to  pathological  processes  of 
life  cannot  at  the  present  time  be  alwaj^s  decided.  From  the  fact  that  the  mussels 
and  oysters  are  poisonous  only  in  certain  places  where  the  water  is  impure,  and  as  the 
starfish  found  in  the  same  localities  are  similarly  affected,  it  is  probable  that  the  poison- 
ous action  of  these  mollusks  may  in  part  be  due  to  their  contamination  with  bacteria 
or  to  the  occurrence  of  certain  diseased  conditions. 

The  venom  of  serpents  is  formed  exclusively  in  the  poison-glands  lying  in  the  upper 
portion  of  the  corner  of  the  mouth.  It  is  a  green  or  yellowish  fluid  and  its  activity  is 
not  influenced  by  drj'ing  or  by  preservation  in  spirits. 

Snake  venom,  the  poisoji  of  spiders  and  toads  and  of  the  blood  of  the  eel  and  murcena, 
ricin  {obtained  from,  the  seed  of  the  castor-oil  bean),  and  abrin  (from  the  seed  Abrvs  preca- 
torius)  show  properties  similar  to  those  of  the  bacterial  toxins  (compare  §11).  Snake- 
poison  and  that  of  the  blood  of  the  eel  have  also  a  haemolytic  action. 

It  is  difficult  to  give  an  exact  definition  of  poison  and  poisoning,  since  the  action 
of  the  sub.stances  considered  in  this  connection  varies  greatly  according  to  the  dose  and 
attenuation,  as  well  as  the  method  of  introduction  into  the  tissues  of  the  body.  The 
most  powerful  poisons  when  introduced  in  minute  doses  may  not  only  be  harmless, 
but  may  exert  a  beneficial  or  curative  effect.  On  the  other  hand,  substances  which  are 
not  usually  classed  with  the  poisons,  such  as  the  non-corrosive  sodium  salts,  when  in- 
troduced into  the  body  in  large  quantities  or  in  concentrated  solutions,  may  produce 
effects  which  must  be  regarded  as  of  the  nature  of  poisoning.  Further,  poisons  in  cer- 
tain dilutions  (phenol)  may  serve  as  food-material. 

Literature. 

(Intoxication.) 

Binz,  Bohm,  Liiebreich:  Arbeiten  deutsch.  Pharmakologen  a.  d.  J.  1865-1889,  Ber- 
lin, 1S90. 

Frohner:    Lehrb.  d.  Toxicologic  f.  Thierarzte,  Stuttgart,  1890. 

Hildebrandt:   Compendium  der  Toxicologic,  Freiburg,  1893. 

Kionka:    Vergiftungen.     Ergebn.  d.  allg.  Path.,  vi.,  Wiesbaden,  1901. 

Kobert:  Lehrb.  der  Intoxicationen,  Stuttgart,  1898;  Compend.  d.  Toxicologic,  Stutt- 
gart, 1894. 

Kunkel:    Handb.  d.  Toxicologic,  i.,  Jena,  1899. 

Lewin:  Nebenwirkung  d.  Arzneimittel,  Berlin,  1899;  Die  Pfeilgifte.  Virch.  Arch., 
138  Bd.,  1894;  Toxicologic,  Wien,  1897;  Cumulative  Wirkung.  Deut.  med. 
Woch.,  1899. 

Loew:   Xatiirliches  Sy.stem  der  Gifte,  Miinchen,  1893. 

Oppenheimer:    Toxine  u.  Antitoxine,  Jena,   1904. 

Roger:    Intoxications.     Path.  gen.  publ.  par  Bouchard,  i.,  Paris,  1895. 

V.  Wyss:    Lehrbuch  der  Toxicologic,  Wien,  1895. 

(Poimning  hy  Spoiled  Foods.) 

Bertarelli:    Gegenw.  Stand,  der  Pellagrafrage.     Centbl.  f.  Bakt.,  xxxiv..  1904. 
Bollinger:   Ueber  Heischvergiftung.     Zur  Aetiologie  d.  Infectionskrankheiten,  Mtu; 

chen,  1881. 
Butter  u.  Huber:    Die  Massenerkrankungen  in  Wurzen,  1877.     Arch.  d.  Heilk.,   .vix, 
Ceni;    (Ui  Astiergilli  nell'  Et.  della  Pellagra.     Riv.  sper.  di  fren.,  xxviii.,  1902. 
V.  During:    Pellagra.     Eulenburg's  Realencyklop.,  xviii.,  1898. 
van  Ermengem:Des  intoxications  alimentaires.  Bruxelles,  1895;  Botulismus.     Zeit. 

f.  Hyg.,  26  Bd.,  1897. 


POISONS.  21 

Flinzer:    Massenerkrankune:     in    rhoinnilz,    1870.     Vierteljalirssclir.     f.    ger.    Med., 

xxxiv..  1881. 
Hiisemann:    Ostreisiiuis  (Austeniv(M-,!:iftiin,<,0.     Kulenburg's  Jahrb.,  vii.,  1897   (Lit.). 
Kaensche:    Krankheitserreger  bei  FlcisclivtM-giftung.     Zeit.  f.  Hyg.,  xxii.,  189G. 
Loinbroso:    Die  Lehre  von  der  Pellajira.  Berlin,  1898. 
Nauwerck:   Wurstvergiftung.     Deut.  nied.  Wochenschr.,  1886;    Wiirtt.  Correspbl.   f. 

Aerzte.  1886. 
Scheube:   Die  Krankh.  d.  warmen  Lander.  Jena,  190;^. 
Schneidemuhl:   Botuli.smus.     Centrall)!.  f.  Bakt.,  xxiv..  1898  (Lit). 
Siedamg-rotzky :   T'elier  Flei.schvorgiftuiii!:.     Vortr.  f.  Tliieriirzte,  iii.  ser.,  2  H.,   1880. 
Silberschmidt:    Fleischvergiftung.     Zcitschr.  f.  Hyg.,  80  Bd.,  1899. 
Vaughan:    Milk- and  Cheese-poisoning.     Zeit.  f.  phys.  Chem.,  1886;  Journ.  of  Amer. 

Mod.  Assn..  1887. 
Yamagiva:   Zur  Kenntniss  der  Kakk^.     Virch.  Arch.,  156  Bd.,  1899. 

(Animal  Poisons. ) 

Aron:   Experimentelle  Studien  iiber  Schlangengift.     Zeitschr.  f.  klin.  Med.,  18S;^. 
ArustamoflF:   Ueber  die  Natur  des  Fischgiftes.     Centralbl.  f.  Bakt.,  x.,  1891. 
Brenning:    Die  Vergiftung  durch  Schlangen,  Stuttgart,  189.5  (Lit.). 
Brieger:   Miesmuschel vergiftung.     Biol.  Centralbl.,  vi.,  1886,  u.  Deut.  mod.    Woch., 

1SS5. 
Calmette:   Venin  des  serpents.     Ann.  de  I'Inst.  Past.,  vi.,  1892;   viii.,  1894;   ix.,  1895. 
Fischel  u.  Enocli:   Zur  Lehre  von  den  Fischgiften.     Fortschr.  d.  Med.,  x.,  1893. 
Husemann:    Fischeifte.     Eulenburg's  Realencyklop.,  1895;  Schlangengifte,  *.,  xxi., 

1S99:    Thiergifte.  ih..  xxiv.,  1900. 
Karlinski:    Zur  Pathologie  der  Schlangenbisse.     Fortschr.  d.  Med.,  viii.,  1890- 
Kaufmann:   Ueber  63  Falle  von  Giftschlangenbissen.     Correspbl.  f.  Schweiz.   Aerzte,. 

1S93. 
Lamb  and  Hanna:  The  Poison  of  Russell's  Viper.     Journal  of  Pathology,  viii.,  1902. 
Langer:   Das  Gift  der  Honigbiene.     Arch.  f.  exp.  Path.,  38  Bd.,  1897. 
V.  Linstow:    Die  Giftthiere,  Berlin,  1894. 

Lustig:   I  microorganismi  del  Mytilus  edulis.     A.  p.  le  Scienze  Med.,  xii.,  1888. 
Mitchell:    Researches  upon  the  Venom  of  the  Rattlesnake,  Washington,  1884. 
Mitchell  and  Reichert:   Venoms  of  Poisonous  Serpents,  Washington,  1886,  ref.  Biol. 

Central.,  vii.,  1888. 
Miura  u.  Takesaki:  Zur  Localisation  des Tetrodongiftes.    Virch.  Arch.,  122  Bd.,  1890. 
Miura  u.  Sumikawa-   Schlangengift.     Centralbl.  f.  allg.  Path.,  xiii..  1902. 
Mosso:   Fn  venin  dans  le  sang  des  murenides.     Arch.  it.  de  Biol.,  xii.,  1888;   u.  Arch. 

f.  exp.  Path.,  XXV,,  1888;  Du  venin  qui  se  trouve  dans  le  sang  de  I'aiguille.     Arch. 

it.  de  Biol.,  xii.,  1889. 
Nowak:    Et.  des  alter,  prod,  paries  venins  des  serpents  et  des  scorpions.     Ann.  de 

rinst.  Pa.st.,.  1898. 
Oppenheimer:    Toxine  und  Antitoxine,  Jena,  1904. 

Ragotzi:    Wirkung  des  Tiiftes  der  Naja  tripudians.     Virch.  Arch.,  122  Bd.,  1890. 
Roger:    Intoxications.     Path.  gen.  publ.  par  Bouchard,  i.,  Paris,  1895. 
Salkowski;   Miesmuschel  vergiftung.     Virch.  Arch.,  102  Bd.,  1885. 
Saotschenko:   Atlas  des  poissons  v^n^neux,  St.  Petersburg,  1887. 
Scheube:    Die  Krankheiten  der  warmen  Lander  (0])hidi.smus),  Jena,  1903. 
Schmidt:    Feb.  d.  Natur  des  Fischgiftes.     Verhandl.  d.  X.  int.  med.  Congr.,  ii.,  Ber- 
lin,  1891. 
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der  Kalachari).      Arch.  f.  exp.  Path..  38  Bd..  1897. 
Thesen:    Vergiftung  durch  Muscheln.     A.  f.  exp.  Path.,  1902. 
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Arch..  104  Bd.,  1886. 
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1S92. 
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See  §  12  for  literature  of  Ptomains  and  Toxins. 


22  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

§  7.  Poisons  may  be  divided  according  to  their  action  into  three 
groups:  first,  those  producing  local  tissue-changes;  second,  those  acting 
injuriously  upon  the  blood;  third,  those  affecting  chiefly  the  nervous 
system  and  the  heart  without  producing  recognizable  anatomical  lesions. 

The  poisons  which  cause  marked  local  lesions  injure  primarily  the 
tissues  with  which  they  first  come  into  contact  upon  entering  the  body.i 
If  such  poisons  are  diffused  by  means  of  the  body-fluids,  the  most 
diverse  organs  and  tissues  may  be  injured;  but  their  action  is  usuallj 
limited  to  that  organ  in  which  they  are  stored  up  or  through  whicl 
they  are  excreted,  especially  the  liver,  intestine,  and  kidneys. 

The  primary  seat  of  injury  is  most  often  the  mucosa  of  the  uppe: 
portion  of  the  intestinal  tract  and  the  respiratory  passages,  but  in  man^ 
cases  the  skin  is  first  affected.  Very  frequently  poisons,  which  are  em 
ployed  for  disinfecting,  are  brought  into  contact  with  wounds  for  th' 
purpose  of  killing  bacteria  or  preventing  their  growth,  and  in  this  wa; 
may  cause  local  changes  or  may  be  absorbed  and  damage  the  internal  or 
gans  or  the  entire  bodj^ 

The  first  great  group  of  poisons  belonging  to  this  class  are  those  whic 
cause  marked  tissue -changes  at  the  primary  point  of  contact,  which  ar 
similar  to  those  of  burns,  and  for  this  reason  have  been  designate 
caustics  or  corrosives.  If  the  action  of  a  caustic  reaches  its  most  chai 
acteristic  severity,  the  affected  tissue  will  be  wholly  destroyed  and  coi 
verted  into  either  a  dry,  hard  eschar,  or  under  certain  conditions  into 
moist,  soft  slough.  If  the  action  is  of  moderate  intensity  as  the  result  ( 
a  less  concentrated  solution  of  the  caustic  agent,  or  of  incomplete  actio 
of  the  chemical  even  when  applied  in  strong  solution  or  in  substanc< 
or  because  the  tissue  itself  is  more  resistant  as  in  the  case  of  the  skin,  tl 
changes  produced  are  much  less  severe,  and  are  characterized  by  re( 
uess,  swelling,  inflammation,  and  haemorrhages.  Very  diverse  chang< 
are  often  found  in  the  same  organ,  such  as  local  sloughing  (necroses 
haemorrhages,  inflammations,  and  small  swellings  due  to  local  hyperaemi; 
If  the  changes  have  existed  for  some  time,  the  local  eschars  are  su 
rounded  by  a  more  or  less  marked  inflammatory  zone,  which  in  the  ca; 
of  certain  caustics  may  be  of  very  limited  exent. 

The  substances  belonging  to  the  class  of  caustic  poisons  are:  first,  the  corrosn 
acids,  sulphuric,  nitric,  hydrochloric,  phosphoric,  oxalic,  arsenic,  arsenious,  osm 
acetic,  lactic,  trichloracetic,  carbolic,  and  salicylic  acids;  and  further,  the  corros'i 
combinations  of  the  alkalies  and  alkaline  earths^  potassium  and  sodium  hydroxi 
(watery  solutions  of  KOH  and  NaOH),  caustic  ammonia  (solution  of  NHs  in  wate 
ammonium  carbonate,  caustic  lime,  and  barium  sulphate.  Belonging  in  this  ck 
are  also  certain  corrosive  salts,  chiefly  of  the  heavy  metak,  such  as  salts  of  antimoi 
(tartar  emetic  and  antimony  trichloride),  salts  of  mercury  (corrosive  sublimate  a  1 
red  precipitate),  nitrate  of  silver,  zinc  chloride,  zinc  sulphate,  copper  sulphate  a  1 
copper  acetate,  aluminum  acetate,  potassiimi  chromate  and  bichromate,  and  chlori 
of  iron. 

The  poisons  belonging  to  this  class  derived  from  animals  are:  cantharidin.  from  t 
beetle  Lytta  vesicatoria;  phrynin,  the  secretion  from  the  cutaneous  glands  (parot: 
of  the  toad;  the  secretions  from  the  poison-glands  of  snakes  and  scorpions;  the  sec 
tion  of  the  sting-gland  of  bees,  wasps,  and  hornets;  the  secretion  of  the  salivary  glar 
of  stinging-gnats,  flies,  and  gad-flies;  and  the  secretion  of  the  poison-glands  of  1 
maxillary  palpa'  of  spiders  (tarantula) — all  of  which  cause  local  necrosis,  or  hsemorrhf 
and  inflammation.  Many  of  the  higher  plants  produce  in  their  blossoms,  seeds,  stems, 
roots  substances  which,  when  brought  into  contact  with  the  tissues,  cause  local  irri 
tion  and  inflammation,  as,  for  example,  daphne,  different  forms  of  Ranunculus,  vai 
ties  of  anemone.  Primula  obconica  (pubescent  portion),  marsh-marigold,  diffen 
varieties  of  Calla,  dragon-root.  Croion  ti<ilii  (from  the  seeds  of  whicli  croton-oil  i 
obtained),  buckthorn  {Rhamnus  cathar(ira).  lilack  elder  (Rhamnus  frangula). 

The  nature  of  the  local  changes  which  these  substances  and  many  others  i  < 


POISONS.  23 

\  mentioned  here  produce  is  naturally  very  varied,  and  is  depenihnt  partly  upon  the 
(activity  of  the  poison,  and  partly  upon  the  location  and  manner  of  application.  The 
[mineral  acids,  solutions  of  caustic  potash  and  mercuric  chloride,  when  concentrated, 
I  cause  marked  tissue-eschars,  associated  with  luemorrhajiie  inflanunations,  especially 
when  taken  into  the  stomach.  Throujrh  the  action  of  acids  there  is  a  marked  with- 
drawal of  the  alkaline  constituents  of  the  body  fluids,  leadinj^  to  disturbances  of  res- 
piration and  circulation.  The  venom  of  snakes  causes  usually  severe  local  inflanuna- 
tions  and  luemorrhapes,  which  often  extend  far  beyond  the  region  of  the  bite,  and 
sometimes  may  cause  also  a  widespread  jianjjrene.  There  are  also  snake-venoms 
which  produce  only  insi<rnificant  local  changes,  the  general  symptoms  of  poi.soninjj 
I  beinir  nuich  more  prominent.  The  roUitilc  or  gaseous  poi.sons,  which  in  the  form  of 
gas  or  vapor  cause  local  irritation  of  the  tissues,  alTect  chiefly  the  nuicous  membranes 
of  the  eye  and  respiratory  tract  {irrespirablc  gases).  To  this  cla.ss  belont:  especially 
the  fumes  of  anunonia,  chlorine,  sulphurous  acid,  nitric  oxide,  nitric  dioxi<le,  nitric  tri- 
oxide,  osmic  acid,  formalin,  and  nuistard-oil.  The  intensity  of  action  of  those  poisons 
is  very  varied,  often  causin<i;  only  a  transitory  hypera-mia.  but  bein>i  able  also  to  give 
rise  to  tissue  necrosis  anil  .severe  inflammation.  The  irritation  of  the  respiratory  tract 
gives  rise  to  coughing  anil  a  spasmodic  narrowing  of  the  glottis  which  may  interfere 
with  breathing. 

To  the  local  irritation  and  inflammation  caused  by  these  poisons  at  the  primary 
ssat  of  contact  may  be  added  further  effects  upon  inlernal  organs.  After  the  absorption 
of  these  poisons  into  the  fluids  of  the  body,  those  organs  suffer  most  in  which  the 
poison  is  stored  up  or  elaborated,  though  organs  of  the  most  varied  structure  may  be 
afTected,  as  well  as  those  not  concerned  in  the  excretion  of  the  poison.  In  the  case 
of  certain  poi.sons,  the  changes  at  the  point  of  entrance  are  very  -slight  and  often  not 
recognizable,  the  important  anatomical  lesions  occurring  first  in  other  tissues,  to  which 
the  poison  has  been  carried  by  the  blood.  Finally,  a  given  poison  may  act  also  as  a 
nerve  and  heart  poison,  so  that  clinically  the  effects  of  this  action  are  much  more  promi- 
nent than  the  local  lesion.  In  poisoning  with  corrosive  sublimate,  cell  necrosis  takes 
l)lace  in  the  .secreting  part  of  the  kidneys,  and  there  is  also  severe  inflammation  of  the 
colon.  The  salts  of  chromic  acid,  cantluiridin ,  and  many  acids  cau.se  more  or  less  marked 
degeneration  and  inflammation  in  the  secreting  portion  of  the  kidney  and  in  the  urinary 
passages. 

Phosphorus,  arsenic,  antimony,  and  pulegon,  which  have  but  slight  corrosive 
action,  produce  tissue-degenerations,  particularly  fatty  degeneration,  and  also  luemor- 
rhages,  in  the  kidneys,  liver,  heart,  muscles,  bone-marrow,  and  capillaries  of  different 
organs,  these  changes  being  particularly  marked  in  cases  of  phos])horus  poisoning. 
According  to  Meyer,  the  cause  of  the  tissue-degenerations  in  phosphorus  jjoisoning  is 
to  be  sought  in  its  action  upon  the  cardiac  nervous  system  and  the  con.sequent  dis- 
turbances of  circulation.  Tischner  believes  that  there  is  a  lesion  of  the  peripheral 
nervous  system. 

If  an  individual  is  exposed  for  months  or  years  to  the  fumes  of  yellow  phosphorus, 
there  may  take  jilace  an  inflammation  of  the  jaw  bones  leading  to  necrosis,  but  only 
when  the  occurrence  of  inflammatory  changes  is  favored  by  other  causes,  such  as 
putrid  decomposition  in  the  mouth  or  the  presence  of  decaying  teeth. 

The  long-continued  use  of  silrer  nitrate  may  be  followed  by  a  deposit  of  black 
granules  of  silver  in  the  most  diverse  tis.sues,  the  skin,  kidneys,  intestinal  villi,  and  the 
choroid  plexus. 

The  venom  of  snakes  possesses,  in  addition  to  its  local  effects,  a  paralyzing  action 
upon  the  nervous  system  and  heart,  and  may  cause  death  through  paralysis  of  the 
respiratory-  centre. 

Soluble  -salts  of  lead  when  ingested  may  cau.se  irritation  and  inflammation  of  the 
intestine,  with  such  .symptoms  as  vomiting,  diarrhoea,  con-stipation,  cramps  in  the 
stomach,  a.ssociated  with  .such  nervous  phenomena  as  anaesthesia,  motor  paralysis, 
convulsions,  vertigo,  and  loss  of  consciousness.  When  ingested  continuously  for  a 
long  time,  lead  gives  rise  to  ana-mia  {.lores),  general  disturbances  of  nutrition,  intes- 
tinal colic,  pains  in  the  limbs,  amesthesia,  motor  paralysis,  cerebnd  flisturbances,  and 
kidney  di.sease.  The.se  disturbances  are  without  doubt  dependent  u|)on  the  distribu- 
tion and  deposit  of  lead  throughout  the  body,  leading  to  anatomical  lesions  of  varied 
nature. 

The  active  principles  of  ergot  {Secale  cornutum),  8phace(imc  arid  and  cornutin. 
when  taken  in  large  doses,  or  when  repeatedly  eaten  in  bread,  catise  itching,  pain,  and 
cramps  in  the  limbs,  followed  by  numbness  and  feeling  of  cold  in  the  toes  .and  finger 
tips,  and  finally  there  may  ai.so  occur  a  more  or  less  exiensive  gangrene  of  these  parts 
{ergfitism.  "KribbelLranhheit'),  at  the  same  time  ulceration  of  the  inl<'stine  may 
occur.  In  cases  of  chronic  poi.soning.  degenerations  of  the  spin:d  cord  t;ike  place 
(Tuczek).     The  feeding  of  chickens  with  ergot  Ciiuses  gangrene  of  th«'  comb  through 


24  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

the  production  of  stasis  and  hyaline  thrombosis  in  the  blood-vessels.  In  animals  fed 
for  a  long  time  with  ergot  degenerative  changes  are  found  in  the  central  and  peripheral 
nervous  system,  in  the  blood-corpuscles,  and  in  the  endothelium  of  the  blood-vessels 
(Grigorjeff). 

Literature. 

(Poisons  Produciny  Local  Tissue- Changes.^ 

Bettmann:  "Wirk.  d.  Arseuiks  auf  Blut  uud  Knochenmark.     Beitr.  v.  Ziegler,  xxiii., 
IS'J.S. 

Brouardel:  Lcs  paralysies  arsenicales.     Arch,  de  med.  exp.,  viii.,  1896  (Lit.). 

Coen  e  D'Ajutolo:  Avvelenamento  cronico  di  piombo.     Beitr.  v.  Ziegler,  iii.,  1888. 

Eichhorst:  Ucber  Bleililhmung.     Virch.  Arch.,  120  Bd.,  1890. 

Erlicki  u.  Rybalkin:  Arseniklahmung.     Arch.  f.  Psych.,  xxiii.,  1892. 

Fraenkel  \i.  Reiche:  Nierenveraud.  nach  Schwefelsaureveraiftung.     Virch.   Arch., 

181  Bd.,  1893. 
Geyer:  Ilautvenind.  bei  Arsenicismus.     Arch.  f.  Derm.,  43  Bd.,  1898  (Lit.). 
Goetze:  Die  Bleivergiftung,  Wurzburg,  1893. 

Grig-orjeflF:  Mutterkornvergiftung.     Beitr.  v.  Ziegler,  xviii.,  1895. 
Griinfeld:  Mutterkornvergiftung.     Dorpater   Arbeiten,   herausgeg.    v.    Robert,   viii., 

1892. 
Hartmann:  Exper.   Untersuchuugen  uber  Chromsaureuephritis.     luaug.-Diss.,  Frei- 
burg,   1891. 
Husemann:     Arsenausschlage    u.    Arsenvergiftuug.     Encyklop.    Jahrb.,    v.,    1895; 

Bleigicht,  ib.,  1897. 
Ipsen:  Salpetersilurevergiftuug.     Vierteljahrsschr.  f.  ger.  Med.,  vi.,  1893. 
Jacobj:  Das  Sphacelotoxin.     Arch.  f.  exp.  Path.,  39  Bd..  1897. 
Janowski:  Die  Ursachen  derEiterung.     Beitr.  v.  Ziegler,  xv.,  1894. 
Jores:    Chron.  Bleivergiftung.    Beitr.  v.  Ziegler,  xxxi.,   1901. 

Kaufmann:  Die  Sublimatintoxication,  Berlin,  1888;  n.  Virch.  Arch.,  117  Bd.,  1889. 
V.  Kahlden:  Die  Aetiologie  und  Genese  der  acuten  Nephritis.     Beitr.  v.  Ziegler,  xi., 

1S92. 
Kobert:  Lehrbucli  der  Intoxicationen,  Stuttgart,  1893. 
Kocher:  Zur  Kenutniss  der  Pliosphornekrose,  Berhn,  1893. 
Kockel:    Wirk.   v.  Dampfeu  salpeteriger  u.  Untersalpetersaure.     Vierteljahrsschr.   f. 

ger.  Med.,  1898. 
Krysinski:  Pathol,  u.  khn.  Beitrage  zur  Mutterkornfrage,  Jena,  1888  (Lit.). 
Lang-erhans :  Verand.  der  Luf twege  nacb  Carbolsaurevergiftuug.     Deut.  med.  Woch., 

1S93. 
Lanz:  Pathogenese  der  mercuriellen  Stomatitis,  Berlin,  1897. 

Lesser:  Verand.  des  Verdauungskanals  durch  Aetzgifte.     Virch.  Arch.    83  Bd.,  1881. 
Leutert:  Sublimatvergiftung.     Fortschr.,  xiii.,  1895. 
Lewin:  Arsen.     Eulenburg's  RealencyklopSdie,  ii.,  1894. 

Lindemann :  Verand.  des  Stoffwechsels  durch  Pulegon.     Zeit.   f.  Biol.,  39  Bd.,  1900. 
Maier:  Bleivergiftung.     Virch.  Arch.,  90  Bd.,  1882. 
Meiser:  Wisnuithvergiftung.     Inaug. -Diss.,  Freiburg,  1892. 
Meyer:  "Wirkung  des  Phosphors.     Arch.  f.  exp.  Path.,  xiv.,  1881. 
Model:  Primula  obconica.    Munch,  med.  Woch.,  1904. 
Mtiller:  Arsenmelanose.     Arch.  f.  Derm.,  25  Bd.,  1882. 
Muir:  Arsenical  Poisoning.     Journal  of  Pathology,  vii.,  1901. 

Neuberg-er:  Wirkuug  des  Sublimates  auf  die  Nieren.     Beitr.  v.  Ziegler,   vi.,  1889. 
Pistorius:  Acute  Arsenikvergiftung.     Arch.  f.  exp.  Path.,  16  Bd.,   1882. 
Riess:  Phosphorvergiftung.     Euleub.  Kealeucyklop.,  xix.,  1899. 
Schultze:  Ueber  Bleilahmung.     Arch.  f.  Psych.,  16  Bd.,  1885. 
Steinhaus:  Verilnd.  d.  Netzhaut  durch  Phosphor.     Beitr.  v.  Ziegler,  xxii.,  1897. 
Tischner:  Unters.  z.  Pathol,  d.  Leber.    Virch.  Arch.,  175  Bd.,  1904. 
TJllmann:  Localisation  d.   Quecksilbermetalle  im  Organismus.     Arch.  f.  Derm.,  Er- 

gilii/h.,  1893. 
"Welander:    Absorption  uud  Elimination  des  Quecksilbers.     Arch.  f.  Derm.,  25  Bd., 

1893. 
Westphal:  Ueber  Encephalopathia  saturnina.     Arch.  f.  Psych.,  19  Bd.,  1888. 
Winternitz:  Allgemeiuwirkung  ortl.  reizender  StofEe.     Arch.  f.  exp.  Path.,  35  Bd., 

1  S<.)5. 
Ziegler  u.  Obolonsky:  Wirkuug  des  Arseniks  u.  des  Phosphors.     Beitr.  v.  Ziegler, 

ii.,  1888.     See  also  i^  6. 


BLOOD-POISONS.  25 

^  8.  The  poisons  irhieh  affect  the  blood  cliirjl//,  and  are  thoi-eforo  termed 
)Iood-poisons,  are  partly  pises  and  partly  lixed  substances.  The  latter 
ire  absorbed  chiefly  from  the  intestine,  but  they  may  also  enter  the  body 
hrou«i,h  wounds,  or  they  may  be  injected  directly  into  the  blood-vessels, 
some  of  the  blood-poisons  may  also  pi'oduce  local  lesions  in  the  tissue  at 
)oint  of  entrance;  further,  there  may  be  joined  to  the  action  on  the 
)lood  a  direct  effect  upon  the  nervous  system,  Mhich  under  certain  con- 
litions  may  cause  death  before  the  action  upon  the  blood  is  recogniz- 
tble.  Finally,  it  should  be  emphasized  that  the  blood-changes  produced 
)y  the  poison  maj"  cause  numerous  secondary  changes  in  different  or- 
gans, for  instance,  iu  the  kidneys,  liver,  intestine,  and  brain. 

Carbon  monoxide,  hj/drort/anie  acid,  potassium  ei/anide,  and  Jii/drof/en 
idphide  form  combinations  willi  luemoglobin  giving  rise  to  caibon-mon- 
(xide-luemoglobin,  cyan-methiemoglobin,  and  sulphur-nu'tluemoglobin, 
herel>y  inhibiting  or  destroying  the  functional  capacity  of  the  red  blood- 
ells.  They  also  produce  an  effect  ui^on  the  ner\-ous  system  which  is 
uost  marked  in  the  case  of  hydrocyanic  acid  and  potassium  cyanide. 
Chese  poisons  in  very  small  doses  iiaralyze  the  central  nervous  system, 
)roducing  death  almost  immediately  through  ])aralysis  of  tlie  centres  of 
espiration  and  circulation. 

Potassium  chlorate,  totui/Jendianun,  bi/drazin,  nitroben,:ol,  nitro(/li/ccrin, 
'nii/I  nitrite,  picric  acid,  phdlin  (a  poison  obtained  fi'om  the  mushroom, 
IfiaricusphaUoidcs),  helve/lie  acid  (poison  of  IlelvcJla  escaJenta),  extractum 
fiticis  maris  ailwreum.  arscniurctted  hydrogen,  and  other  substances  cause 
lest  ruction  and  luemolysis  of  the  red  blood-cells  and  lead  in  part  to  the  for- 
iiation  of  methfemoglobin,  that  is,  to  an  oxygen  combination  of  hsemo- 
jlobin,  the  oxygen  content  of  which  is  the  same  as  that  of  oxyhjemo- 
jlobiu,  but  in  which  the  oxygen  is  bound  more  firmly  than  in  the  latter. 

Certain  bacterial  products  which  are  called  bacterial  hcemolysins  have 
lIso  a  specific  action  upon  the  red  blood-cells,  leading  to  the  production 
>f  hfemoglobina?mia.  The  best  known  are  those  occurring  in  infec- 
ions  with  the  tetanus  bacillus  and  staphylococcus  and  aic  known  as 
etanolysin  and  staphylolysin. 

When  the  blood  of  an  animal  is  introduced  into  the  blood  stream  of 
nan  or  of  an  animal  of  another  species,  specific  hcemolysins  become  active, 
hat  is,  poisons  which  cause  htemolysis  of  the  foreign  red  blood-cells. 

Carbon-monoxide  poisoning  most  often  results  from  the  carbon  monoxide  in  coal- 
ir  illuminating-^as,  but  may  occur  under  otlier  conditions,  as  in  the  case  of  vapors 
)roduced  by  gun-powder  or  gun-cotton.  The  effects  of  the  inhalation  of  carljori  mon- 
>xide  result  from  the  combination  of  the  gas  with  the  hu-nioglohin  of  llic  Mood  and 
he  formation  of  carbon-monoxide-hiemoglobin.  The  amount  of  oxygon  coinbincd  with 
he  hemoglobin  is  thereby  decreased,  and  the  taking  up  of  oxygen  is  reduced,  even 
v'hen  the  respired  air  contains  only  0.05  per  cent  or  even  0.02  per  cent  of  (X)  ((h-ubcr). 
rhe  red  blood-cells  themselves  present  no  changes.  A  rapid  supply  of  carbon  monoxide 
o  the  nervous  .sy.stem  may  cause  direct  injurj^  to  the  nerves,  giving  rise  to  convulsions 
md  later  to  paralysis  (Geppert).  In  cases  of  long-continued  poi.soning  the  displace- 
nent  of  the  oxygen  from  the  greater  portion  of  the  red  cells  leads  to  tissue-asphyxia. 
i  the  affected  "individual  does  not  die,  there  may  result,  in  addition  to  the  poisoning, 
levere  disturl)ances  of  nutrition,  occurring  especially  in  the  nervous  sy.stem.  The 
)oisoning  itself  is  characterized  by  headache,  tinnitus  aurium,  vertigo,  malaise,  vomit- 
ng,  fainting,  convulsions,  paralysis,  and  coma.  The  l)lood,  as  a  result  of  the  presence 
)f  carbon  monoxide,  becomes  a  bright  violet  or  cherry-red  color,  so  that  the  hypera-mic 
ikin  and  internal  organs  al.so  appear  bright  red. 

Ili/ilrocj/anic  acid  {('Nil)  is  found  in  unstable  combination  in  the  leaves,  bark,  and 
;eeds  of  many  plants  (bitter  almonds,  cherry-  and  peach-stones,  apple-seeds,  leaves  of 
;he  laurel,  bark  of  Prunus  padus,  tubers  of  many  of  the  Euphorbiaceie,  flax.seetl,  etc.). 
°otas^um  cyanide  (CNK)  is  used  in  many  of  the  technical  arts.     The  action  of  both 


26  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

of  these  poisons  upon  the  blood  is  the  formation  of  cyanmethoemofilobin,  which  gives 
the  blood  a  bright  red  color  and  produces  a  bright  red  post-mortem  lividity. 

Hydrogen  sulphide  (//-.S)  is  a  constituent  of  the  gas  of  sewers  and  dung-pits.  "When 
inhaled  in  large  amounts,  it  may  cause  sudden  death  from  paralysis  of  the  nervous 
system.  When  hydrogen  sulphide  is  for  some  time  brought  into  contact  with  blood 
containing  oxygen  (as  is  usually  the  case  in  decomposing  cadavers),  a  sulphur-met  hae- 
moglobin is  formed,  which  gives  to  the  blood  a  greenish  color. 

The  poisons  that  dissolve  the  red  blood-cells,  in  part  with  the  formation  of  methanno- 
globin,  belong  partly  to  the  oxidizing  substances  (ozone,  iodine,  sodium  hypochloride, 
chlorates,  nitrites,  and  nitrates);    partly  to  the   reducing   agents  (nascent   hydrogen,    | 
palladium   hydride,   pyrogallol,   pyrocatechin,    hydrochinon,   and   alloxanthin);     also 
and  partly  to  substances  which  have  neither  a  reducing  nor  oxidizing  action  (salts  of 
aniline  and  toluidin,  acetanilid).     In  the  transformation  of  hjemoglobin  into  methse-    j 
moglobin  through  oxidizing  substances,  oxj^hsemoglobin  is  present  as  an  intermediate    ; 
stage.  ...  ' 

The  formation  of  methaemoglobin  can  occur  either  in  the  red  blood-cells  or  in  the  I 
hfemoglobin  which  has  escaped  into  the  blood-plasma;  but  the  destruction  of  the  blood- 
cells  and  the  escape  of  htemoglobin  into  the  plasma  are  not  always  followed  by  the 
formation  of  methiemoglobin.  In  the  case  of  a  marked  destruction  of  red  cells,  as  in 
poisoning  from  phallin,  helvellic  acid,  arseniuretted  hydrogen,  only  a  portion  of  the 
hajmoglobin  is  changed  into  methaemoglobin.  Haemoglobin  and  oxyhsemoglobin  have 
a  red  color,  methaemoglobin  a  sepia-brown. 

Dissolution  of  the  red  blood-cells  and  the  formation  of  methaemoglobin  occur  in  j 
the  case  of  a  part  of  those  poisons  causing  local  tissue-changes,  as  in  poisoning  with  ( 
acids,  metallic  salts,  phosphorus,  arsenic,  and  snake-venom.  I 

Verj'  large  doses  of  potassium  chlorate  {CIO3K)  may  cause  death  in  a  few  hours  i 
through  the  destruction  of  red  blood-cells  and  the  action  of  the  potassium,  with  the 
occurrence  of  vomiting,  diarrhoea,  dyspnoea,  cyanosis,  and  cardiac  insufficiency.  The 
lilood  becomes  chocolate-brown  in  color.  In  more  protracted  cases  of  poisoning 
through  smaller  doses,  products  of  blood  destruction  are  found  in  the  spleen,  liver, 
l)one-marrow,  and  kidneys;  and  the  urine  may  show  a  brown-red  to  black  color  (met- 
haemoglobin). Delirium,  numbness,  coma,  and  con\Tilsions  occur  during  the  course  of 
the  intoxication,  showing  that  the  central  nervous  system  suffers  severely.  Pyrogallol 
(CeHe,[OH]s)  produces  similar  effects;  hydrazin  {H^N — XH.^)  and  phenylhydrazin 
cause,  in  addition  to  haemolysis  and  the  formation  of  methaemoglobin,  multiple  throm- 
boses. In  poisoning  with  toluylendiainin  {C M i[N H -^.C H -.,)  the  chief  action  is  the 
destruction  of  red  blood-cells  leading  to  deposits  of  iron-containing  pigment  in  the 
spleen,  liver,  and  bone-marrow.  In  cats  methaemoglobin  may  be  excreted  through  thv^^ 
urine  {Biondi).  In  poisoning  with  picric  acid  {CJI-^NOi]  uOH)  there  occurs,  in  addition 
to  the  blood  changes  and  the  formation  of  methaemoglobin,  a  severe  irritation  of  the 
central  nervous  system  finding  expression  in  violent  convulsions.  Aniline  (Ce/ZsAWo) 
acts  in  a  similar  manner,  and  carbon  bisulphide  (C.S2)  not  only  produces  changes  in  the 
blood  but  also  irritates  and  causes  paralysis  of  the  central  nervous  system. 

According  to  Robert,  7'icin  derived  from  the  seeds  of  the  castor-bean,  and  abrin 
from  the  .seeds  of  abrus  precatorius,  should  be  classed  with  the  blood-poisons,  in  that 
in  the  test-tube  they  cause  an  agglutination  of  the  red  cells  and  the  formation  of  a 
tlocculent  precipitate.  In  animals  poisoned  experimentally,  local  irritations,  tissue- 
degenerations  and  inflammations,  similar  to  those  caused  by  certain  bacterial  toxins,  are 
produced,  as  well  as  disturbances  in  the  centres  of  the  medulla  oblongata,  leading  to 
cessation  of  respiration  with  progressive  falling  of  blood-pressure.  Tissue-degenera- 
tions, inflammation,  and  haemorrhage  are  found,  after  longer  action,  at  the  point  of 
application  and  in  the  intestine,  where  the  poison  is  excreted.  Degenerative  changes 
are  also  found  in  lymphocytes,  liver  and  kidney  cells,  and  heart  muscle. 

Literature. 

(Blood- Poisons  ;  Abrin  and  Ficin.) 

Afanasiew:  Vergiftung  niit  Toluylendiamin.     Zeitschr.  f.  klin.  !Med.,  6  Bd.,  1883. 
Belky:  Zur  Kenntniss  der  Wirkung  der  gasformigen  Gifte.     Virch.  Arch.,  lOG  15d., 

isso. 
Berkley:  Ricin-poisoning.     Trans,  of  the  Path.  Soc.  of  Philadelphia,  xviii.,  1898. 
Biondi:  Experimcutelle  Untersuchungeu  ilber  Hamatolyse.     Beitr.  v.  Ziegler,  xviii., 

l^sy,-). 
Bohm  u.  Ktilz:  Giftiger  Bestandtheil  d.  Morchel.    Arch.  f.  exp.  Path.,  19  Bd.,  1885. 
Bostroem;  Intoxication  durch  die  essbare  Morchel,  Leipzig,  1882. 


NERVE-  AND    IIEAKT-POISOXS.  27 

Jramer:  Befuiul  im  Gchiru  bci  Kohleuoxyilvcrs^iftuui'.     Ct'iitralhl.  f.  alia;.  Patli  ,  iv  . 

1S94. 
ruz:  Alt.  liist.  daus  rcmpois.  jmr  la  riciue.     Arch,  do  mod.  oxp..  xi..  18<J9. 
)ittrich:  Uebor  inetliamosrlohinbildendc  Giftc.     Arch.  1".  v\]k  Patli.,'.2()  Bd.,  1S92. 
)reser:  Zur  Toxikologie  des  Kohleuoxyds.     Arch.  f.  cxj).  Path.,  29  Bd..  1S91. 
Palkenberg:  ^■l^gitt.  durch  Auilia,  chlorsaure  Sal/.e  u.  .Sublimat.     Yirch.  Arch.,  1','3 

Bd.,  isjil. 
''lexner:  Hist.  Chang,  prod.  byBicinand  Abrin.     Jour,  of  Exp.  ^Ivd.,  18'J7,  rcf.  Cent. 

1'.  a.  Path.,  18!)!). 
Jeorgiewsky :  Wirkung  des  Extract,  filicis  maris  aeth.    Beit,  von  Zicgler,  xxiv.,  1898. 
jreppert:   L'cber  das  Weseu  der  Blaiisaurevergiftung.     Zeitschr.  f.  klin.  J\Ied.,  15  Bd  . 

ISS!). 
Jeyer:  Chrou.  Ilautveraudcrungcu  bci  Arseuicismus.     Arch.  f.  Derm.,  4o  Bd.,  1898 

(Lit.). 
aCeinz:  Blutdegeneration    u.  Regeneration.    B.  v.  Ziegler,  xxix.,  1901;  Exp.  Path.  I., 

.bna,  190-t. 
Eiiber:    Giftwirkimg  des  Diuitrobenzols.     Yirch.  Arch.,  126  Bd.,  1891. 
Eusemann:    Pilzvergiftuug.     Euleub.  Realencyklop.,  xix.,  1898  (Lit.). 
Katayama:    2seue  Blutprobeu  bei  Kolilenoxydvergiftuug.     Yirch.  Arch.,  114  Bd., 

ISSS. 

Kionka:    Blutgifte.     Ergebu.  d.  allg.  Path.  v.  Lubarsch,  vii.,  1902. 

Kobert:    Lchrbucli  der  Intoxicationen,  Stuttgart,  1893. 

Koch:    Sch\varz\vassert]eber  (Chininvergiftuiig).     Zeit.  f.   Hyg.,  30  Bd.,  1899. 

Lebedefif:    3[orchelvergiftung.     Yirch.  Arch.,  91  Bd.,  1883. 

Lewin:    Xebenwirkung  d.  Arzneimittel,  Berlin,  1899;  Toxikologie,  Wien,  1897. 

Marcacci:    Empoisonnement  par  I'oxyde  de  charbon.     Arcli.  ital.  de  Biol.,  xix.,  1893. 

Marchand:    Wirkung  chlorsaurer  Salze.     Arch.  f.  exp.  Path.,  23  Bd.,  1886;u.  23  Bd., 

IssT. 
V.  Mering:    Das  chlorsaure  Kali,  Berlin,  1885. 
Mtiller:    Ricinvergiftuug.     Arch.  f.  exp.   Path.,  42  Bd. ;  u.   Beit.    v.  Ziegler,   xxvii., 

1>I0(I. 
Oppenheimer :    Toxine  u.  Autitoxlne,  Jena,  1904. 
Petrone:  Avvelenamento  da  aci(U)  piroi^allico,  Catania,  1895. 
Ponfick:  31<.rchelvergiftung.     Yirch.  Arch.,  88  Bd.,  1886. 
Poelch.en:  Gehiruerweiehuug  uach  Kohlendunstvergiftung.     Yirch.  Arch.,  112  Bd., 

ISSS. 

Silbermann:  Blutgerinnung  durch  chlors.  Salze,  Arsen,  Phosphor,  etc.     Yirch.  Arch., 

117  Bd.,  1889. 
Stadelmann :  Yergiftung  mit  Toluylendiamin.     Arch.  f.  exp.  Path.,  14  Bd.,  1881,  16 

Bd..  1883,  23  Bd.,  1887;  Der  Ikterus,  Stuttgart,  1891. 
Stephens:  Haniolytic  Action  of  Snake  Toxins.     Jour,  of  Path.,  vi..  1900. 
Stockvis:  Yergift.  mit  chlorsaurem  Kali.     Arch.  f.  exp.   Path.,  10  Bd.,   1897;  u.   21 

Bd..  1S86. 
CTschinsky:  SchAvefelwasserstoffvergiftung.     Zeitschr.  f.  phys.  Chem  ,  17  Bd.,  1892. 
Werhovsky:  Abrin vergiftung.     Beit,  v,  Ziegler,  xviii.,  1895. 

§  9.  Tlie  last  group  of  poisons,  generally  classed  together  as  nerve 
ind  heart  poisons,  is  characterized  chieliy  by  the  fact  that,  in  spite  of  the 
severity  of  tlio  .symptoms,  as  shown  in  the  form  of  irritations  and  paraly- 
ses, anatomical  changes  either  cannot  be  recognized  at  all  or  are  conlined 
to  structural  changes  in  the  protoplasm  of  individual  nerve-cells,  which 
ire  of  similar  character  in  the  case  of  dilferent  poisons.  This  is  espe- 
[jiaTly  the  case  when  the  poison  is  quickly  fatal,  Miiile  if  the  poisoning 
runs  a  protracted  course,  or  in  the  case  of  chronic  poisoning  from  small 
loses,  extending  o\er  months  and  years,  there  are  very  often  found 
marked  anatomical  changes — a  fact  which  may  be  taken  as  evidence  that 
these  poisc^ns  do  not  })ro(hice  solely  functional  disturbances  of  the  ner- 
vous .system,  ])ut  cansc  iiijuiy  to  thecell-i:notoplasm  which  may  be  mani- 
fested in  the  form  of  degenerations. 

Of  the  Aery  great  ninnl)er  of  poi.son.s  u-hich  act  especUiJhj  upon  the,  ner- 
vous system  nud  nmy  aiui^o,  deatli  llirongli  its  paralysis,  the  most  impor- 
lant  are:  chloroform,  chloral  hydrate,  alcohol,  ether,  opium  and  its 
dkaloid  morphine,  cocaine,  atropine,  hyo.scyamine,  daturine  (.stramoui- 


28  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

uni-atropine),  nicotine,  coniiue,  eicutoxin,  santonin,  qninine,  veratriue, 
eolchieiiie,  aeonitine,  strychnine,  cytisin,  curarine,  and  samandarine 
(salamander-poison). 

Of  the  heart -poisons,  digitalin,  helleborin,  muscarine,  and  phryuin 
(poison  of  toads;  are  of  special  importaDce. 

CJtloroform.  (CIWU),  when  applied  directly  to  the  inucous  membranes,  causes 
local  irritation  and  may  produce  transitory  inflammation.  When  conveyed  to  the  blood 
tlirough  iniialalion  or  by  absorption  from  tlie  intestinal  tract,  it  gives  rise,  after  a 
short  "period  of  stimulation,  to  a  condition  of  diminished  irritability  of  the  cerebral  gray 
and  white  matter.  According  to  Binz,  the  protoplasm  of  the  ganglion-cells  suffers  a 
slight  coairulation.  Death  may  be  caused  by  paralysis  of  the  central  nervous  system, 
as'xvcll  as"^l)v  a  premature  heart-failure;  the  latter,  however,  occurring  only  when  the 
heart  is  abnormally  weak  or  degenerated.  Certain  individuals  show  an  especial  sus- 
ceptibility lo  the  action  of  chloroform.  The  long-continued  use  of  chloroform  may 
cause  degenerative  changes  in  different  organs,  as  the  heart,  kidneys,  liver,  muscles, 
and  blood. 

Et/ie?'  {diethyl  ether  CiHiOCJh)  acts  sitnilarly  to  chloroform,  but  is  less  poisonous, 
and  acts  less  detrimentally  upon  the  heart. 

yiiroiis  oxide  (N-xO)  acts  chiefly  upon  the  cerebrum,  lowers  the  sensibility  of  pain, 
and  paralyzes  consciousness;  later,  the  action  may  extend  to  the  spinal  cord,  the 
medulla  oblongata,  and  the  heart. 

Alcohol  (C^IIiOII),  after  a  transitory  stimulation,  has  a  depressing  and  paralyzing 
action  upon  the  brain,  at  the  same  time  causing  a  dilatation  of  the  arteries  of  the  skin, 
so  that  in  intoxicated  individuals  severe  chilling  through  the  skin  may  easily  occur. 
Death  may  take  place  suddenly,  with  symptoms  similar  to  those  of  apoplexy ;  more 
frequently  there  is  a  gradual  loss  of  consciousness  and  of  sensory  perception,  the  respira- 
tion becomes  slower,  the  pulse  small,  the  face  cyanotic;  complete  coma  and  general 
paralysis,  forming  the  closing  symptoms.  The  immoderate  use  of  alcohol  for  months 
or  years  may  cause  degenerative  atrophies  of  liver  and  kidneys  associated  with  increase 
of  connective  tissue;  further,  sclerosis  and  atheroma  of  the  arteries,  degeneration  of  the 
brain,  etc.,  are  ascribed  to  the  action  of  alcohol.  At  the  present  time  it  is  impossible 
to  say  in  what  manner,  how  often,  and  to  what  extent  these  changes  are  dependent 
upon  the  use  of  alcohol.  Much  is  ascribed  to  the  action  of  alcohol  that  is  not  in  any 
way  caused  by  it  and  is  due  wholly  to  the  action  of  other  injurious  agents.  It  is  cer- 
tain, Jiowever,  that  drunkards  suffer  frequently  from  disturbances  of  digestion  and 
circulation,  catarrhal  inflammations  of  pharynx,  larynx,  and  bronchi,  and  disturbances 
of  cerebral  function ;  and  that  the  disease  of  the  brain  known  as  delirium  tremens, 
wliich  is  cliaracterized  by  general  muscular  tremors,  obstinate  insomnia,  anxiety,  and 
hallucinations,  is  especially  to  be  ascribed  to  alcoholism. 

Chloral  hydrate  (CClsCIIO.IliO)  causes  local  irritation  of  mucous  membranes,  and 
through  the  blood  produces  paralysis  of  the  brain,  spinal  cord,  and  heart,  and  thus  in- 
duces sleep.  In  fatal  doses,  death  follows  deep  coma  as  a  result  of  oedema  of  the  lungs 
due  to  the  general  relaxation  of  the  tissues. 

Opium  and  Morphine  (CnHio^Oi)  depress  the  cerebral  functions,  thereby  inducing 
sleep;  in  individual  cases  there  may  be  a  preceding  period  of  stimulation.  Large  doses 
lead  to  unconsciousness,  paralysis  of  muscles,  slowing  and  weakening  of  the  heart's 
action,  contraction  of  the  pupils,  slowing  of  intestinal  peristalsis,  diminution  in  the  ex- 
change of  gases  in  the  blood  dependent  upon  (iiniiuished  excitability  of  the  respiratory 
centre.  There  is  no  characteristic  autopsy  flnding;  the  blood  is  usually  dark  and  fluid. 
The  chronic  use  of  opium  may  give  rise  to  digestive  disturbances,  emaciation,  vertigo, 
sleeplessness,  neuralgias,  imbecility,  impotence,  weakness  of  the  bladder,  hallucination, 
tremors  of  the  hands  and  feet,  fever,  etc.,  yet  these  symptoms  may  vary  much  in 
dilTerent  individuals.  In  chronic  morphinism  the  organism  becomes  accustomed  to 
increasingly  larger  doses;  withdrawal  of  the  drug  causes  severe  nervous  disturbances, 
and  under  certain  conditions  dangerous  collapse. 

Cocaine  {CnlhiAOt)  produces  peripherally  a  dulling  of  the  excitability  of  the 
.sensory  nerve-endings;  centrally,  first  a  stimulation  and  later  a  paralysis.  The  chronic 
use  of  cocaine  gives  rise  to  symptoms  similar  to  those  of  chronic  morphinism. 

Atropine  and  hi/oscj/amine  {Cnlh^MOi),  the  alkaloids  which  are  found  in  the 
SolanaceiP  (deadly  nightshade,  thornapple,  and  henbane),  cause  paralysis  of  the  periph- 
eral niTve  organs  and  a  central  stimulation,  followed  later  by  paralysis.  Solutions 
of  atropine  introduced  into  the  eye  produce  dilatation  of  the  pupil  and  paralysis  of  ac- 
commodation for  near  vision,  through  its  paralyzing  action  on  the  endings  of  the  motor 
oculi  ill  the  iris.  Atropine  may  further  cause  suppression  of  the  secretion  of  certain 
glands  (as  the  submaxillary) ;  it  also  inhibits  intestinal  peristalsis.  Asa  result  of  the 
action  of  this  poison  upon  the  brain,  a  condition  of  excitement,  gayety,  inclination  to 


NERVE-    AND    II KAHT-POISONS,  29 

lauixli.  leailinir  evcu  to  insanity  and  frenzy,  may  be  produced,  followed  by  paralysis. 
The  autopsy  tinditigs  are  negative. 

yir»t/nt'  (r,„y/n3'o),  ii  vohitile  alkaloid  found  in  the  tol)aeco  ])lHnt,  acts  upon  both 
perijiheral  and  central  nervous  systems,  ciiusing  nausea,  siilivation,  vomiting,  diarrha-a, 
vertigo,  nuiscle-weakness,  headache,  convulsions,  delirium,  and  paralysis.  Chronic 
nicotine  poisoning  may  give  rise  to  nervous  alTectious  and  disturbances  "of  the  heart's 
action. 

Coniine  {dHnN),  the  alkaloid  present  in  hemlock,  causes  paralysis  of  the  periph- 
eral motor  nerve-endings,  first  stimulating  and  tlien  paralyzing  the  central  nervous 
system.  Cicutoxin,  a  poisonous  resin  obtained  from  the  water-hemlock  {Cicuta  rirona) 
produces  nausea,  vomiting,  attacks  of  colic,  cardiac  palpitation,  convulsions,  and  un- 
consciousness. 

S,i)i(o/ii>i.  (CisIli^Oa)  causes  convulsions  by  its  action  on  the  brain  and  spinal  cord, 
with  benumbing  of  the  sensorium,  vertigo,  vomiting,  salivation,  and  yellow  vision  or 
xanthopsia,  in  which  white  is  seen  as  yellow  and  blue  as  green. 

Quinine  {C-2oII-i4^''iOn),  the  most  important  of  the  numerous  alkaloids  contained  in 
the  bark  of  cinchona  and  other  closely  related  plants,  has  a  i)aralyzing  action  upon 
living  protoplasm,  and  in  relatively  small  doses  lowers  the  functional  capacity  of  the 
brain.  Large  doses  produce  death  "through  paralysis  of  the  centre  of  respiration  and  of 
the  heart. 

Arouitine,  calchicine,  and  ro-dtrine  produce  local  irritations  and,  later,  benumbing 
of  the  peripheral  endings  of  the  sensory  nerves.  On  the  central  nervous  system  the}' 
have  rirst  a  stimulating  action,  later  a  paralyzing. 

Stri/chnine  {Cn^H^^S^Oi),  obtained  chietly  from  the  plant  nux  vomica,  causes  an 
increased  reflex  excitability  of  the  nerve  centres,  so  that  the  slightest  external  stimu- 
lus may  produce  tetanic  convulsions.  Death  may  occur  in  from  ten  to  thirty  minutes 
after  the  first  convulsion,  and  is  the  restdt  of  central  paralj^sis,  namely,  of  the  vaso- 
motor centre. 

Curanne  {CiiHiiN),  the  active  principle  of  the  arrow-poison  curare,  is  probably 
derived  from  the  cortical  portion  of  the  roots  of  dill'erent  plants  of  the  strychnia  family. 
When  used  in  small  doses  it  paralyzes  the  endings  of  the  motor  nerves  of  the  muscles. 
Larger  doses  cause  paralysis  of  the  central  nervous  system  and  of  the  vasomotor 
nerves,  after  a  teraporarj^  stimulation. 

lJi(jitalin  and  digitalein,  two  glucosides  obtained  from  the  foxglove,  act  as  local 
irritants;  after  absorption  they  stimulate  the  heart,  vagus-centre,  and  the  musculature 
of  the  blood-vessels,  so  that  with  a  slowing  of  the  heart-beats  there  is  an  increase  of 
blood-pressure.  Large  doses  cause  headache,  delirium,  tinnitus  aurium,  irregular  in- 
crease in  the  frequency  of  the  heart's  action,  convulsions,  and  coma. 

//<'Z?<'6o/7'«,  a  glucoside  obtained  from  hellebore,  acts  similarly  to  the  preparations 
of  digitalis. 

Muncarine  (C-^Hi^yOa),  the  poison  of  the  fly-agaric,  acts  as  a  stimulant  to  those 
nerve-endings  which  are  paralyzed  by  atropine.  The  intense  excitation  of  the  inliib- 
itory  centres  of  the  heart  causes  stoppage  of  the  unparalyzed  heart,  and  deatii  is 
thereby  produced.  The  general  symptoms  of  muscarine  poisoning  are  salivation,  ver- 
tigo, anxiet}',  nausea,  vomiting,  diarrhoea,  convulsions,  and  finally  unconsciousness. 
Small  doses  produce  a  condition  of  excitation  similar  to  that  of  drunkenness. 

Literature. 

(Xn-ve-  and  JTrari-Pol'iotis.) 

Abderhalden :  Alkohol  (Bibliographic).     Wien,  1904. 

Afanasiew:   Zur  Path,  des  acuten  u.  chron.  Alkoholismus.     Beitr.  v.  Ziegler,  viii., 

isiio. 
Ambrosius:  Tod  nach  Chloroforminhalation.     Virch.  Arch.,  138  Bd.,  Suppl.,  1894. 
Binz:  Das  Chinin,  Berlin,  1875;  Alkohol.     Eulenl)urg's  Uealenc  yklop..  iii.  Aufl.,  1K93. 
Braun:  Veriind.  d.  Nervensj^stems  dnrch  chron.  Alkoholinto.xication,  Tubingen,  1899. 
Brouardel:  Les  paralysies  aVsenicales.     Arch,  denied,  exp.,  viii.,  is!)(j  (Lit.). 
Demme :    Ueber  den  Einfluss  des  Alkohols  auf  den  Organismus  des  Kindes,  Stuttgart, 

1N90. 
Denys-  Zur  Kenntniss  der  WirkungdesStrychnins.    Arch.  f.  exp.  Path.,  20  Bd.,  1886, 
Duclaux:    L'alcool.    Ann.  de  I'lnst.  Pasteur,  1903. 

Faust.  Zur  Kenntn.  d.  Samaudarins.    Arch.  f.  exp.  Palli.,  41  Bd.,  1898. 
Fraenkel,  C. .  .Aliissigkeit  oder  Enthaltsamkeit '/  Berlin,  1903. 
Fraenkel,  E. ,  Veranderungen  durch  Chloroformnachwirkung.    Virch.  Arch.,  127  Bd., 

is;)2. 


30  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

Garre:  Tiiv  Aetliernaiknse,  Tubingen,  1893. 

Goldscheider  u.   Flatau:    Norniale   u.  i)atliol.   Aiiatoniie  der  Nervcnzcllen,    Berlin, 

INKS. 

Husemann:  Pfeilgifte.     Eiilenburg's  Realeucyldop.,  xviii.,  1898. 
Jacottet-   l-:t.  sur  Ics  alterations  des  cellules  uerveuses.    Beitr.  v.  Ziegler,  xxiv.,  1897. 
V.  Kahlden-  Wirkung  des  Alkohols  auf  Leber  u.  Niereu.    Beitr.  v.  Ziegler,  ix.,  1881. 
Kobert:  .Muscarinwirkung.     Arch.  f.  exp.  Path.,  20  Bd.,  1886;  Intoxicationcn,  Stutt- 

-ari.  is<j;l 
Kraepelin:  Psych.  Wirkung  des  Alkohols.    Miinch.  med.  Wocli.,  1899. 
Kunkel:     llandb.  d.  Toxikologie,  Jena,  1899. 
Lewin:  Die  Nebenwirkuug  d.  Arzneimittel,  Berlin,  1899;  Pfeilgifte.     Yirch.   Arcliiv, 

V.'.r,  Bd.,  1894. 
Ostertag:  Die  todtliche  Xarhwirkuiig  des  Chloroforms.     Virch.  Arch.,  118  Bd.,  1889. 
Poroscliin:   Veriind.  durcli  t'hionitornuiarko.se.     Cbl.  f.  d.  ined.  AViss.,  1898. 
Strassmann:  Todtliclie  Nachwlrkung  des  Chloroforms.     Virch.  Arch.,  115  Bd..  1889. 
Striimpell:  Die  Alkoholfrage   vom  arzll.    Standpunkt  aus.      ^Mliuch.    med.    Woch., 

1893. 
Tillie:  Ueber  d.  Wirkung  des  Curare  u.  seiner  Alkaloide.     Arch.  f.  exp.  Path.,  27  Bd., 

189U. 


4.     OrUjin  of  Disease  ihrongh  Infeetlon  or  Parasitism. 

§  10.  The  entrance  of  living  organisms  from  the  outer  world  into  the  tissues 
of  the  human  or  animal  body,  and  their  multijiJieation  there  with  the  liroduc- 
tion  of  pathological  processes,  is  kuowii  as  infection.  Since  these  orgau- 
isius  take  their  food  from  the  tissues,  they  are  during  their  stay  in  man 
or  in  animals  to  Ix^  regarded  as  parasites,  and  therefore  the  affections 
known  as  lh(^  infectious  diseases  are  nothing  more  than  parasitic 
conditions. 

Tiie  i)ai-asites  causing  the  majority  of  the  infectious  diseases  are  now 
known.  In  those  diseases  in  wliich  they  are  not  yet  discovered  (small- 
])0x,  measles,  scailatinii,  etc.)  the  existence  of  a  parasite  may  be  assujued 
through  tlie  peculiarity  of  the  infectious  disease;  and,  indeed,  through 
tlie  fact  tiiat  for  infection  only  the  smallest  imponderable  amount  of  in- 
fect iv<'  material  is  necessary,  so  that  the  severity  of  the  disease  can  be 
ex])laiiicd  only  through  the  assumption  of  an  increase  of  the  harmful 
agent  witliin  tlie  l)ody;  and,  further,  through  the  fact  that  the  disease 
in  question  is  characterized  by  definite,  constantly  recurring  phenomena 
and  by  a  typical  course.  It  may  happen  that  a  given  disease  may  spread 
from  one  affected  individual  to  other  individuals,  giving  rise  to  a  pesti= 
lence  or  epidemic,  which  may  spread  throughout  one  house  or  city  or 
tlirougliout  the  whole  land  or  over  many  lands.  The  spread  of  the  dis- 
ease occurs  sometimes  in  such  a  way  that  one  gets  the  impression  that 
thei-e  is  a  direct  passage  from  man  to  man,  a  direct  contagion  (diph- 
theria, smallpox,  measles,  influenza,  whooping-cough,  gunoi'rluea,  syph- 
ilis, and  lejirosy);  at  other  times,  as  if  the  causal  agent  of  the  disease 
clung  lo  certain  regions  as  a  so-called  miasma  (malaria),  and  from 
thence  infected  the  individuals  who  came  into  its  neighborhood;  finally, 
at  other  times,  as  if  the  disease  liad  been  spread  through  an  affected  in- 
dividual, who  had  acquired  the  disease  somewhere  and  had  then  changed 
his  residenci^  and  had  infected  the  new  place  of  residence  in  some  way 
or  other,  .so  that  the  inhabitants  there  acquired  the  disease.  Infections 
that  ni;iy  be  spicad  by  this  last  method  may  be  designated  miasmatic 
contagious  diseases  r  Asiatic  cholei-a.  yellow  fever,  typhoid). 

The  parasites  that  cause  the  infectious  diseases  belong,  accoiding 
to  our  present  knowledge,  foi-  the  greater  part  to  the  schizomycetes 
or  bacteria;  but  certain  of  the  higher  plants,  the  mould-fungi  ('eumy= 


INFECTION.  "T 

cetes),  and  \\\o  yeasts  may  also  causo  iiifoclions  diseases.  Fiirtlici-,  llic 
animal  parasites  are  also  represented  by  imnierous  species,  l>el(tn.L;inLi  in 
part  to  the  protozoa,  in  part  to  the  worms,  and  paitly  to  the  arthropoda. 
It  has  been  the  custom  to  accord  to  the  animal  i)arasites  an  especial 
position,  since  many  of  them  do  not  increase  in  tlie  host  in  whom  they 
live,  but  pass  only  tlu'ouiih  certain  sta<ies  of  development  without  cans- 
ing  such  symptoms  as  are  characteristic  of  the  infections  diseases.  Such 
adistinction  will  not  lu)ld,i;ood,  since  ty])ical  infectious  diseases  (nndaria) 
may  also  be  caused  by  animal  i)ai"asitt'S.  Further,  in  the  case  of  many 
of  the  animal  ])aiasites  a  definite  increase  does  take  j)lace  within  *lie 
human  oi'i;anism. 

AN'ith  the  recognition  that  the  infections  diseases  a r(>  canst'd  thi-ough 
the  parasitism  of  minute  living-  mirrovrf/anlwifi  not  visible  to  the  naked 
eye,  the  view  Avas  soon  reached  that  pure  contagious  diseases  must  be 
caused  by  parasites  that  could  thrive  only  within  the  human  or  animal 
organisms;  while  miasmatic  diseases  arose  throngh  living  agents  Avliich 
occnr  in  the  outer  world  and  occasionally  gain  cntj-ance  into  man  oi'  ani- 
mals. In  the  tii'st  case  the  microorganisms  were  designated  oidof/ruons 
p((r<isit('s,  in  the  second  ectof/rnoiis.  It  was  assumed  in  ivgaid  to  the 
miasmatic  contagious  diseases  that  the  microcirganisms  c<>idd  increase 
either  within  the  body  or  in  the  outer  world;  but,  in  the  latter  place, 
only  when  they  passed  from  the  human  or  animal  body  into  water,  food, 
or  earth. 

With  certain  limitations  this  view'  is  still  to-day  regarded  as  correct; 
but,  according  to  later  experiences,  its  original  application  is  not  always 
correct,  since  many  microorganisms  that  ordinarily  increase  oidy  in  liv- 
ing tissues  as  i:)arasites  i-equire  for  their  gi'owth  outside  of  the  hnnian 
body  certain  conditions  of  life  that  make  their  multiplication  possible, 
so  tiiat  in  a  certain  sense  a  contagium  may  become  a  miasma.  The  causal 
agents  of  measles,  scarlatina,  and  of  syphilis  can  develop  only  inside  of 
the  human  body ;  that  of  smallpox,  within  the  body  of  man  and  cattle, 
and  we  have  not  yet  succeeded  in  growing  them  in  artificial  media. 
Tubercle  bacilli  ordinarily  develop  only  in  the  tissues  of  man  and  ditfer- 
eut  vertebrates;  but  they  may  be  cultivated  on  certain  media  at  the  tem- 
perature of  the  body,  and  subsequently  can  be  successfully  inoculated 
into  man  and  animals.  Staphylococci  and  streptococci,  which  ])i'odnce 
suppurations,  anthrax  bacilli,  typhoid  bacilli,  cholera  s))iiilla,  and  others 
glow  easily  in  very  different  solid  and  Huid  media  and  can  aftei-  such  an 
artificial  cultivation  cause  disease  in  man,  both  thi-ongh  contagion  and 
through  transmission  from  the  outer  world.  But  it  should  be  noted 
that,  even  in  the  last-named  cases,  the  bacteria  concerned  have  often  not 
increased  in  the  outer  world,  so  that,  for  example,  water  used  for  drink- 
ing becomes  oidy  the  conveyer  of  the  infective  agent. 

]\Ialaria,  which  is  considei-ed  the  chief  type  of  a  miasmatic  disease,  is 
produced  by  a  microcnganism,  which,  <»utside  of  the  human  body,  must 
pass  through  definite  stages  of  de\  eloi)nu'nt  in  certain  mos<piitoes  or  it 
will  die.  Through  the  taking  up  of  blood  frcmi  a  malarial  i)atieiit  the 
infected  mosquitoes  (different  forms  of  Ano])heles)  i-epresent  the  malaria- 
producing  miasm,  and  man  is  again  infected  through  their  bite,  and  not, 
as  was  originally  supposed,  through  mists  ai'ising  from  marsln-s  or  through 
bacteria.  It  is  also  possible  to  lu'odnce  an  infection  with  malaria  by  tli(; 
transfusion  of  blood  from  a  malarial  patient  to  a  In-altiiN   imli\  idnal. 

The  view  that  certain  diseases,  particularly  epidemics,  were  of  parasitic  nrifnin,  is 
very  old,  and  found  expression  in  the  works  of  Kirchner  (I602-IG80),  Lancisi  (1654- 


32  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

1720),  Litinc  (1707-1778),  and  others.  It  has  been  left  to  verj^  recent  times,  however, 
to  place  the  theory  of  the  parasiiic  natureof  the  infectious  diseases  upon  a  secure  founda- 
tion. Though  several  decades  ago  Henle.  Liebermeister,  and  others  asserted  that  the 
peculiarities  of  infectious  diseases  could  be  explained  only  by  the  assumption  of  a 
contaqium  animaium,  the  establishment  of  this  doctrine  is  due  to  the  results  of  the 
investigations  of  the  last  thirty  years.  .     ,.      , 

The  climate  is  often  held  responsible  for  the  ongui  of  disease,  and  we  are  mcimed 
to  consider  a  region  having  a  uniform  temperature,  much  sun,  and  little  wind  as  a 
healthy  one.  whUe  one  having  marked  variations  of  temperature,  abundant  precipita- 
tion, little  sun.  and  much  wind  is  regarded  as  unhealthy.  This  is  true  to  a  certain 
extent,  in  so  far  as  invalids  or  individuals  susceptible  to  the  influences  of  weather  are 
concerned,  but  a  much  more  important  and  decisive  criterion  of  the  healthfulness  of  a 
region  is  the  presence  or  absence  of  specific  agents  of  disease,  vegetable  or  animal 
parasites  that  may  infect  man.  Such  disease-producing  agents  may  exist  in  affected 
members  of  the  population  of  the  regioii,  in  the  drinking-water,  in  the  earth,  or  in  animals 
etc.  In  the  tropics  the  malarial  parasites  play  the  most  important  role,  their  trans- 
mission to  man  being  brought  about  through  the  agency  of  mosquitoes.  Therefore, 
the  most  beautiful  region  which  seems  to  offer  the  best  climate  may  be  unhealthy; 
while  raw,  cold,  and  inhospitable  regions  may  be  very  healthy  through  the  absence  in 
them  of  the  causal  agents  of  disease. 

Literature. 

(Infections. ) 

Aoyama:   Mitteil.  iiber  die  Pestepidemie  in  Hongkong,  Tokio,  1895  (ref.  Cent.  f.  Bakt., 

xix.). 
Bouchard:   Les  microbes  pathogenes,  Paris,  1892. 

Charrin:    L'infection.     Path.  gen.  publ.  par  Bouchard,  ii.,  Paris,  1896. 
Daubler:    (Iruiidziige  der  Tropenhygiene,  Berlin,  1900. 
Duclaux:    Le  microbe  et  la  maladie,  Paris,  1886. 

Fear:   Scharlach,  Maseru,  Rotheln.     Ergebn.  d.  allg.  Path.,  iv.,  1899. 
Fltigg-e;    Die  Mikroorganismen,  Leipzig,  1896;  Verbr.  d.  Cholera.     Zeit.  f.  Hyg.,  xiv., 

l.S9;5  (Lit.). 
Galtier:    Traite  des  maladies  contagieuses  des  animau.x    domestiques,   2d  ed.,  t.  i., 

Paris,   1891. 
Haeser:   Geschichte  der  Medicin  u.  der  epidemischen  Krankheiten,  i.-iii.,  Jena,  1875- 

1S,S2. 
Hecker:    Die  grossen  Volkskrankheiten  des  Mittelalters,  her.  von  A.  Hirsch,  Berlin, 

ISCm. 
Hirsch,  A.:    Handh.  der  historisch-geogr.  Pathologic,  i.  and  ii.,  Stuttgart,  1881-1886. 
Kolle  uiid  Wassermann:    Handb.  d.  pathogenen  Microorganismen,  i.-iii.,  Jena,  1903. 
Koch  uiid  Gaifky:    Ber.  ub.  d.  Thatigkeit  der  zur  Erforschung  der  Cholera  im  Jahre 

188:^  nach  Egvpten  u.  Indien  entsandten  Kommission.    Arb.  a.  d.  K.  Gesundheits- 

amte,  iii.,  Berlin.  1887. 
Laveran:    Les  maladies  ('pi(l('>nii(|uos.      Path,  gen.,  ii.,  Paris,  1896. 
Liebermeister:    LelxT  (li(>  lis.ichci!  dci-  \'()lkserkrankung.,  Basel,  1865. 
Lofflev:    rel)or  die  geschiclitliche  Eiitwickelung  der  Lehre  von  den  Bakterien,  Leipzig, 

1SS7. 
Mannaberg:    Die  Malariakrankheiten,  Wien,  1899. 

Marchiafava  and  Bignami:    :\Ialaria.     Twent.  Cent.  Pr.,  xix.,  New  York,  1900. 
Rog-er:    Les  maladies  infectieuses,  Paris,  1902. 
Rumpf:   Die  Cholera  indica  und  nostras,  Jena,  1898. 
Scheube:   1  )ie  Krankheiten  der  warmen  Lander,  Jena,  1903. 
Schncidemtihl:    N'crgieichende  Pathologie  d.  Menschen  u.  d.  Thiere,  Leipzig,  1895 

Virchow:   Ccs.  Abhandl.  a.  d.  Gebiete  d.  off.  Med.  u.  d.  Seuchenlehre,  i.  and  ii.,  Berlin, 

1S79. 
Weichselbaum:    Epidemiologic,  Jena.  1S99. 

See  also  §  12. 

S  11.   Tlic  bacteria  are  small,  iiiiicclliilai'  oi-gaiiisms,    Avliich  appear 
ii!  tlie  f(»nii  of  lit  tic;  spheres  (cocci),  and  liuc,   straight,  or  curved  rods 
(l)acilli  and    si)irilla),   frequently    uniting    in    peculiar   combinations,     j 
3I:niy   jxtsscss  motile  organs   in  the    form  of  flagella.     Under  especial    I 


s 


IXFF.CTION.  33 

conditions  some  of  tlieni  produce  sixjics  or  ix'culiar  ])crni;uH'nt  I'ornis, 
mostly  oval  in  sliai>e. 

Fi'OHi  tlio  standpoint  of  the  pliysician  bacteria  may  bo  divided  into 
the  non=pathogenic  and  the  pathogenic.  To  the  hitt«M-  belong  all  those 
that  are  able  to  increase  in  the  hnnian  and  animal  ori;anism.  Jhd  this 
classihcation  is  not  altogether  satisfactory,  inasmuch  as  pathological  con- 
ditions may  be  caused  by  bacteria:  that  are  not  able  to  increase  within 
living  tissues.  This  rests  upon  t he  fact  that  all  bactei-ia,  not  only  the 
pathogenic,  but  also  the  non-pathogenic,  in  their  growth  in  initritive 
media  (albumin,  peptone,  gelatin,  non-nit I'ogenous  media),  decompose 
these,  and  thereby  often  jH'oduce  substances  that  are  toxic  for  man  and 
for  the  higher  animals.  These  changes  in  the  nutritive  media  ai-e  brought 
about  chietly  by  the  action  of  J'omotis  and  enzi/me.s,  the  latter  ])i-ocess 
being  regarded  as  a  direct  function  of  the  living  cell  substance,  while  the 
former  is  due  to  the  action  of  ferments  or  enzymes  that  are  liberated 
from  the  cells. 

The  most  important  of  the  substances  produced  by  the  decomposition 
of  proteids  are  the  nitrogenous  basic  cadaveric  alkaloids  or  ptomains, 
many  of  which  are  poisons  for  man.  For  example,  the  toxic  i»roducts 
neniiilin,  cadaveriu,  putrescin,  neurin,  and  methylguanidin,  the  last 
three  of  which  are  poisons,  may  be  obtained  in  pure  form  fiom  decom- 
posing meat.  If  these  enter  with  the  food  into  the  human  body  symp- 
toms of  intoxication  may  be  produced  without  any  develo])ment  of  bac- 
teria in  living  tissue.  On  the  whole,  their  activity  is  not  consideicd  very 
great,  and  it  is  questionable  whether  the  artificially  produced  poisonous 
ptomains  ever  arise  during  the  processes  of  decomposition. 

Besides  the  prof>erty  of  producing  ptomains  and  other  poisonous  sub- 
stances (for  example,  hydrogen  sulphide),  which  belongs  to  many  differ- 
ent bacteria,  the  pathogenic  bacteria  produce  other  poisons  specific  for 
the  individual  species.  The  first  of  these  to  be  considered  are  the  toxins 
in  the  narrowei"  sense,  that  is,  j)oisonous  substances  which  do  not  belong 
to  the  ptomains  and  are  also  not  albuminous  bodies  (toxalbumins). 
They  are  the  products  of  secretion  of  the  bacterial  cells  and  can  be  sepa- 
rated by  filtration  from  the  bacteria.  The  most  important  rei)]-esenta- 
tives  of  such  poisons  are  those  produced  by  the  bacUU  of  diphiheyhi  and 
tetanus,  both  in  cultures  and  in  the  human  organism.  It  is  ])robable  also 
that  cholera  sj)irilla  produce  them  in  small  aniount.  The  toxins  are  very 
unstable  bodies  and  quickly  lose  their  activity  through  lieating  above 
50"  C,  the  effect  of  light,  and  through  the  action  of  acids  and  other 
chemical  substances;  when  dry  they  will  stand  100°  C  without  injury. 
Their  chemical  structure  is  not  known;  they  may  be  compared  Mitli  the 
enzymes.  Their  activity  is  also  limited  to  the  animal  susceptible  to 
the  given  disease.  When  injected  into  susceptible  aniimds,  theii-  action 
fakes  place  after  a,  jyeriod  of  incubation  known  as  the  period  oflatenei/.  lu 
the  affected  organism  they  cause  the  production  of  antibodies  or  antitoxins, 
which  render  the  toxin  harmless  in  the  organism  and  also  neutralize  it 
in  vitro. 

As  a  second  form  of  specific  poison  there  occur  intracellular  toxins 
or  endotoxins,  that  is,  poisons  which  cling  to  the  bacterial  cell  and  are 
separated  from  it  only  with  difficulty.  Even  less  is  known  of  their 
nature  than  of  the  true  toxins.  Typhoid  bacilli,  cholera  sjjirilla,  and 
pneumococci  form  such  poisons,  and  it  has  been  assumed  that  they  be- 
come active  after  the  destruction  of  the  bacteria  in  the  linman  organism. 
I  A  third  form  of  bacterial  i)oison  is  found  in  the  bacterial  proteins  or 
3 


34  THE    EXTRINSIC    CAUSES    OF   DISEASE. 

micoproteins,  that  is,  tlie  substance  of  the  bacterial  cell  itself.  They 
prodiu-t' chietlv  a  local  effect,  liiKliug-  expression  in  intiammatory  proc- 
esses. II  is  vtMv  pr(tl)able  that  such  a  local  action  occurs  in  all  bacte- 
rial iiif.'clioiis  ill  Avhicli  the  bacteria  develop  locally.  If  the  bacteria 
coiiccriiecl  pi'oduce  antitoxins  the  action  of  these  is  combined  with  that 
of  the  bacterial  i)roteins. 

Ill  individual  cases  it  is  very  often  impossible  to  decide  to  what  ex- 
tent ptomains  or  to  wluit  extent  specific  bacterial  toxins  and  micoproteins 
are  concerned  in  the  production  of  the  pathological  condition.  Tlie 
term  bacterial  toxin  is  very  often  used  in  a  broad  way  to  cover  all  of 
the  ])()is()ii()iis  substances  produced  by  bacteria. 

8(»iue  pathogenic  bacteria  increase  first  in  the  outer  world  (for  exam- 
ple, the  tetanus  l)acillus),  and  only  occasionally  do  they  develop  in  the 
linmau  or  animal  l)()dy ;  on  the  other  hand,  other  forms  develop  ordi- 
narlhi  onlji  in  the  human  or  aninml  orqanism  (tubercle  bacilli,  glanders, 
lepi'osy,  dii)htheria,  and  influenza  bacilli)  and  need  for  their  development 
outside  of  the  body  especial  nutritive  media,  or,  indeed,  they  cannot  be 
cultivated  at  all.  Others  still  increase  with  especial  energy  in  human  and 
animal  tissue,  but  are  also  easili/ grown  upon  different  nutritive  media  (strepto- 
coccus, staphylococcus,  anthrax  bacillus,  typhoid  l)acillus,  cholera  spiril- 
lum), and  are  also  able  to  multiply  under  natural  conditions  in  the  outer 
woild. 

The  distribution  of  pathogenic  bacteria  from  the  affected  individ- 
ual to  the  outer  world  takes  place  through  coughing,  sneeziug,  expec- 
toration, speaking,  through  intestinal  and  urinary  discharges,  secretion 
from  wounds,  sloughing  of  portions  of  tissue,  etc.  When  thrown  out 
into  the  air  they  may  remain  floating  for  some  time  and  be  carried  to 
some  distance,  but,  sooner  or  later,  they  become  attached  to  some  object. 
Through  drying  and  through  sunlight  many  of  them  are  quickly  de- 
stroyed, cithers  remain  alive  for  a  certain  period,  often  a  very  long 
time,  especially  in  the  form  of  spores,  and  may  be  found  in  either  a  dry 
or  moist  state,  in  the  water  or  in  the  earth.  If  they  find  the  proper  food- 
material  and  if  the  temperature  is  high  enough  for  their  development, 
the  bacteria  may  multiply. 

Fi'om  the  ])lace  where  they  are  thrown  down,  or  from  the  objects  to 
which  they  cling,  or  where  they  have  undergone  further  development, 
the  bacteria  may  later  suffer  a  wider  distribution.  Stronger  currents  of 
air  may  cai-ry  them  farther  away,  especially  from  the  objects  to  which 
they  simply  cling,  or  also  in  the  dust  of  the  room  or  of  the  street.  Many 
of  them  are  brought  to  the  human  and  animal  organism  imrtly  through 
food  and  drink,  partly  through  the  air,  and  i)artly  through  contamina- 
tions of  the  fingei's. 

TIk^  avenues  of  entrance  for  bacteria  are,  in  general,  the  mucous 
meinl)ranes  of  the  intestinal  canal,  respiratory  tract,  and  the  middle  ear, 
the  conjunctiva,  the  alveoli  of  the  lungs,  and  open  wounds.  But  it 
should  b(>  noted  that  many  bacteria  are  able  to  gain  an  entrance  only  in 
certain  tissues,  for  example,  the  typhoid  bacillus  and  the  cholera  spiril- 
lum gain  entrance  only  from  the  intestine  and  not  from  the  skin  or  lung. 
Through  recent  wounds,  both  pathogenic  and  non-pathogenic  bacteria 
ai-e  rai)idly  taken  u]>  into  the  lymph  and  blood;  while  through  wounds 
showing  iieallhy,  gi'anulating,  uninjured  surfaces,  the  entrance  of  many 
bacteria  into  the  tissues  is  hindered.  Pathogenic  bacteria  (pus  cocci) 
uot  infre(|U(Mitly  enter  through  the  uninjured  skin,  either  by  way  of  the 
hair-follicles  or  through  the  sebaceous  or  sweat-glands.     Under  especial 


IXFECTIOX.  35 

?oiKlitioiis  (coitus,  surgical  operations,  dribbling-  of  urine,  childbirth) 
[he  inlection  may  take  its  start  from  the  mucous  membranes  of  tlie  uro- 
i;enital  tract.  Some  infections  may  be  liansmitted  by  insects,  which 
jave  taken  up  bacteria  with  tlie  l)h)od  or  seeretions  of  a  diseased  indi- 
ridnal  or  animal,  oi',  having  become  conlaniinatcd  extei'nally  by  sueh, 
nay  infect  an  open  wound  l)y  sci'ai)iug  the  bacteria  oil"  theii-  legs  ujion 
he  exposed  suilace,  or  by  the  direct  iulro(biction  of  gei-ms  into  the  skin 
>r  accessible  mucous  nuMubranes  during  the  act  of  stinging  oi- sucking. 
[f  nu'at  containing  bacteria  be  eaten,  and  if  the  animal  while  ali\  e  was 
itfected  by  an  infectious  disease  which  also  occui's  in  man,  this  pai-ticu- 
ar  disease  may  be  ti-ausmitted  to  man,  in  case  the  bactei-ia  had  not  been 
jreviously  destroyed. 

Bacteria  arrive  at  the  point  of  entrance,  sometimes  in  association  with 
chemically  acti^•e  substaiu'cs,  sonu'times  without  such;  tlu^  Ihst  is  more 
ikely  to  occur  in  the  intestinal  tract,  the  secontl  in  the  resi>iiatory  pas- 
sages and  in  the  lungs;  yet  chemical  substances  nuiy  also  iind  their  way 
nto  the  lungs  with  bacteria,  aud  bacteria  may  enter  the  intestiual  canal 
;vithout  the  association  of  chemically  active  material. 

If  toxic  bacterial  products  enter  in  considerable  amount  into  the 
ntestinal  canal  or  wounds  at  the  same  time  with  the  bacteria,  the  symp- 
oms  of  an  intoxication  may  be  produced  without  an  infection,  that  is, 
ivithout  an  increase  of  the  bacteria  in  the  tissue  taking  place.  This 
?vent  may  also  happen  wheu  bacteria  producing  such  poisons  develoj)  in 
he  contents  of  the  intestine,  in  wound-secretions  or  in  necrotic  lung  tis- 
sue, and  increase  there  as  saprophytes.  Strictly  speaking,  we  cannot  re- 
gard this  as  an  infection,  but  must  look  upon  the  disease  so  produced  as 
lu  intoxication;  but  it  is  uot  always  possible  iu  such  cases  to  draw  a 
sharp  line  between  an  intoxication  and  an  infection,  since  bacteria  origi- 
lally  developing  as  parasites  uot  infrequently  penetrate  into  the  tissues 
lud  there  multiply. 

Intestinal  intoxications  dependent  upon  bacterial  toxins  occur  es- 
pecially when  meat  or  duids  in  a  condition  of  bacterial  decomposition 
lave  been  eaten  as  food.  To  such  intoxications  belong  a  lai-ge  ]>i()])or- 
ion  of  the  affections  designated  as  meat-,  sausage-,  fish-,  and  cheese-poison- 
ng,  in  which  the  poisou  is  either  taken  as  such  into  the  intestinal  canal, 
)r  first  formed  there.  Likewise,  many  vegetables  in  a  condition  of 
"ermentation  and  decomposition,  for  example,  cabbage,  peas,  beans, 
torn,  rice,  etc.,  exert  a  harmful  influence  upon  the  intestine  or  upon  the 
Entire  organism,  especially  when  they  have  been  eaten  iu  large  amounts 
|)r  for  a  long  period  of  time.  !J\or  infrequently  there  occur  also  acute 
■)oisouings  of  the  same  kind. 

If  the  bacteria  which  have  entered  the  body  through  one  of  the 
iibove-meutioned  avenues  of  infection  are  in  a  strict  sense  pathogenic,  so 
ihat  they  give  rise  to  an  infection,  they  may  increase  first  at  the  point 
^>f  entrance,  in  the  intestinal  mucous  nu-mbrane,  in  a  wound,  in  tlie 
jkin,  etc.  The  local  effects  of  their  growth  are  dependent  prinuirily 
jipon  the  individual  characteristics  of  the  bacteria,  as  well  as  upon  the 
.)eculiarities  of  the  affected  tissue.  In  general,  the  local  action  is  char- 
cterized  by  tissue-degenerations,  necrosis,  inflammations,  and  new-for- 
nation  of  tissue,  so  that  it  is  possible  in  many  cases  to  determine  the  na- 
urc  of  the  infection,  that  is,  the  species  of  bacteria  causing  the 
II  feet  ion,  from  the  character  of  the  local  changes.  It  is,  however, 
illicultor  impossible  to  determine  in  every  case  the  exact  mode  of  ac- 
lou  of  the  multiplying  bacteria;  iu  general,  it  uiav  be  said  that  the 


36  THE    EXTRIXSIC    CAUSES    OF    DISEASE. 

processes  of  cbemical  metamorphosis  excited  by  the  multiplication  of  the 
bacteria  produce  certain  changes  iu  the  tissue-cells,  lu  that  different  sub- 
stances of  active  chomical  nature  either  kill  the  cells,  or  at  least  induce 
degenerative  changes  in  them,  or  iu  part  excite  increased  cell-activity. 
In^the  furtlier  development  of  the  process  the  substances  derived  from 
dead  and  dissolving  bacteria  may  also  produce  effects  upon  the  surround- 
ing tissue.  In  a  certain  sense,  therefore,  there  occurs  through  the  local 
growth  of  bacteria  a  local  intoxication,  which  is  of  far  greater  significance 
than  the  withdrawal  of  nutritive  material  through,  the  consumption  by  the 
bacteria  of  food  substances.  The  latter  is,  however,  not  wholly  without 
significance,  inasmuch  as  the  chemical  changes  produced  by  the  bac- 
teria iu  the  tissue  juices  often  render  these  unfit  for  the  nourishment  of 
the  tissue-cells,  so  that  the  cells  suffer  even  when  no  poisonous  substances 
are  produced. 

The  participation  of  the  entire  organism  in  a  local  bacterial  infec- 
tion may  be  very  slight  or  wholly  absent,  so  that  the  disease  appears  as 
a  purely  local  affection  (tuberculosis).  In  other  cases  the  toxins  and 
toxalbnmins  formed  iu  the  local  focus  of  infection  are  absorbed  into  the 
body  fluids  (i.e.,  into  the  blood),  and  a  general  intoxication  (toxinwmia) 
is  produced ;  that  is,  poisonous  effects  are  exerted  upon  the  nervous  sys- 
tem, sometimes  upon  the  blood  itself  and  upon  the  heart;  and  the 
poisons  thus  taken  into  the  body  may  i^roduce  demonstrable  changes  iu 
the  internal  organs,  particularly  in  the  excretory  glands,  at  times  also  iu 
the  skin.  In  many  diseases  (tetanus,  typhoid  fever,  streptococcus  and 
staphylococcus  infection,  diphtheria)  the  symptoms  of  poisoning  are  es- 
pecially prominent. 

If  iiealing  does  not  take  place  iu  the  primary  seat  of  infection,  thei 
neighboring  tissues  may  be  involved  by  an  invasion  of  bacteria  by  con-; 
tinuity.  Very  often  the  bacteria  gain  entrance  to  tlie  lymph=vessels; 
or  blood-channels  (bacteriwmia),  and  in  this  way  are  transported  and 
spread  over  the  entire  body.  The  result  of  this  metastasis  of  bacteria  is 
the  production  of  a  lymphogenous  or  hsematogenous  infection  ;  that' 
is,  secondary /oci  of  disease  identical  in  character  with  the  jyrimarij  seat  of 
infection  are  formed  at  a  distance  from  the  primary  focus.  In  certain 
diseases  (tuberculosis,  suppurations,  plague)  the  number  of  metastases 
is  usually  very  great,  so  that  many  parts  of  the  body  (lymph-glands, 
li\er,  lung,  brain,  muscles,  bones,  kidneys,  etc.)  may  contain  diseased 
foci.  On  the  other  hand,  in  other  infections  metastasis  of  bacteria 
from  the  original  focus  to  other  organs  does  not  occur  (tetanus,  diph- 
theria), or  the  transported  bacteria  cause  only  changes  of  a  milder  type 
(typhoid  fever). 

Th(!  entrance  of  bacteria  into  the  blood  leads  to  bacteriaemia.  Dur-:| 
iug  the  ti-ansportatiou  of  bacteria  through  the  blood-vessels,  there  is' 
usually  no  increase  of  the  bacteria  in  the  cii'culating  blood,  the  blood 
serriiirj  onlji  as  a  vehicle  to  carry  the  bacteria  to  other  parts  of  the  body, 
multii)licatiou  occurring  first  at  those  points  where  the  bacteria  have^ 
come  to  rest.  Xevertheless,  in  certain  infections  (anthrax)  the  bacterial 
increase  enormoushj  in  the  circulating  blood,  and  iu  this  way  may  cause' 
damage  to  the  bhjod  itself.  Through  the  obstruction  of  small  blood-ves- 
sels by  tlie  multiplying  bacteria,  there  may  be  added  to  the  intoxication 
also  local  disturl)auces  of  circulation. 

The,  metastasis  of  bacteria  or  toxic  substances,  or  both,  from  a  local- 
ized seat  of  infection,  and  the  production  thereby  of  secondary  foci  and. 
symptoms  of  intoxication,  give  rise  to  the  condition  which  is  generallyl 


BACTERIAL    INFECTION.  37 

terniiHl  sepsis.  According  to  tlic  prodoininant  syiiii)toiiis  llioro  may  be 
iistiiiiiuished  a  scptcvmia  or  scpiicwitiia,  a  pi/auiiia  and  :i  li/iiip/i(nif/oitis. 
rbrongh  1  lie  combination  of  both  the  hitter  wit  h  sept  icaMiiia,  scjtfiropifa'mia 
is  prodnced.  Originally  the  designation  septicaemia  Mas  applied  to 
:hose  cases  in  Avliich  a.  localized  infection  was  associateil  Mith  info.ricdfion 
caused  by  liacterial  ])oison  or  a  toxincvniia  withont  the  spi-ead  of  bacteria 
hrongh  the  body.  At  tlie  pi-esent  time,  according  to  the  precedent  Kset 
n'  Koch,  (Jatfky,  and  others,  sei)tica'niia  is  nsed  to  designate  the  con- 
lition  characterized  by  the  entrance  of  both  l)acteria,  and  tlieir  ])ois()ns 
nto  the  blood,  a  coincident  to.rin<vi)ti(i  and  hdcicyiwrnid  :  indeed,  by  many 
luthors  the  pure  intoxication  or  toxiniemia  is  separated  from  septiciemia. 
The  term  pyaemia,  originally  signifying  a  metastasis  of  pus  tlirough 
he  blood,  is  at  ])resent  employed  to  designate  the  condition  in  Avliich 
he  metastasis  of  bacteria  gives  rise  to  the  formation  of  metastatic  ah- 
\cesses. 

In  septicopyaemia  the  symptoms  of  toxinoemia  and  bacteria^mia  are 
combined  with  the  formation  of  metastatic  foci.     Lymphangoitis  is  an 

nflammation  of  the  hjmpli-vesseJs  and  their  surroundings  caused  by  trans- 
)orted  bacteria. 

Sepsis  in  its  different  forms  is  most  frequently  caused  by  the  true 
pyogenic  organisms,  sta])h)ilococcns  jmogenes  aureus,  and  the  streptococeus 
pyogenes,  but  similar  conditions  also  occur  in  infection  with  the  jJneu- 
nococeus,  gonocoeeus,  typhoid  bacillus,  colon  haclRus,  2)l(igue  bacillus,  etc. 

If  bacteria  are  deposited  secondarily  in  the  body-passages  which  are 
ined  with  mucous  membiane,  as  in  the  respiratory  or  urogenital  tract, 
hey  may  multiply  within  these  tracts  and  produce  their  characteristic 
pathological  changes.  Likewise,  they  may  multiply  also  within  the 
arge  body=cavities,  in  the  peritoneal,  pleural,  and  subarachnoid 
paces.  In  the  case  of  an  infection  occurring  in  a  pregnant  woman, 
aany  varieties  of  bacteria  (anthrax,  symptomatic  anthrax,  glanders, 
recurrent  fever,  typhoid,  pneumonia,  the  pyogenic  bacteria,  tubercu- 
osis)  may  be  transmitted  to  the  foetus. 

The  description  given  above  of  the  course  of  an  infection  may  be 
aken  as  a  general  type,  and  many  infectious  run  such  a  course  (typhoid, 
>ya^mia,  erysipelas,  plague,  diphtheria,  tetanus,  tuberculosis,  syphilis, 
eprosy,  glanders,  actinomycosis,  etc.);  but  there  aie  also  many  devia- 
ions  fi-om  this  scheme.  In  the  first  place,  it  not  infrequently  happens 
hat  in  an  infection  which  in  general  runs  a  typical  course,  the  primary 
eat  of  infection  is  not  demonstrable,  either  because  no  changes  occuii-ed 
.t  the  point  of  entrance,  or  the  changes  prodnced  luive  since  disap- 
»eared.  Such  forms  of  infection  are  known  as  cryptogenic;  they  may 
>e  lymphogenous  or  hsematogenous.  It  is  typical  of  many  infections 
hat  the  primary  localization  of  the  cause  of  tlie  disease  is  not  recogniz- 
ble,  so  that  general  symptoms  occur  before  local  changes  are  demonstrable, 
,nd  the  tissue-changes  occurring  later  have  moi-e  the  character  of  a  sec- 
ndary  localization  of  tlie  jyoison  of  the  disease.  This  occurs  esi)ecially  in  a 
lumber  of  infectious  diseases,  the  causes  of  which  are  unknown  tons; 
or  example,  in  scarlet  fever,  smallpox,  and  measles;  yet  in  many  in- 
ections  whose  causes  ai-e  known  we  are  not  always  able  to  discover  at 
^hat  point  the  first  multi])lication  of  the  bacteria  occuis.  Thus  we 
:now  that  in  relapsing  fever  tin;  si)irilla  are  found  in  the  blood  in  large 
umbei's  at  the  time  of  the  fever,  l)ut  the  i)lace  of  their  multiplication  is 
uknowu  to  us. 


38  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

IsTot  infrequently  a  secondary  infection  may  be  joined  to  one  already 
present.  In  many  oases  the  association  is  entirely  accidental,  in  other 
cases  the  anatomical  changes  i^rodnced  by  the  first  infection  cause  a 
local  predisposition  to  the  new  invasion.  To  the  first  group  would  be- 
long, for  instance,  a  croupous  pneumonia  occurring  in  an  individual 
suffering  with  tuberculosis  of  the  kidney  or  bones;  while  the  occurrence 
of  an  infection  with  cocci  causing  suppuration  and  septic  intoxication 
during  the  course  of  typhoid,  influenza,  diphtheria,  scarlet  fever,  dysen- 
tery, caseous  ulcerating  tuberculosis,  etc.,  may  be  regarded  as  due  to  the 
production  of  local  tissue-changes  favoring  the  entrance  of  bacteria. 
These  secondary  infectious  usually  aggravate  the  sufferings  of  the  patient 
in  that  a  new  independent  disease  is  added  to  the  one  already  present; 
but  it  may  also  happen  that  the  organisms  entering  secondarily  into  the 
body  grow  oidy  as  saprophytes  in  exudates  or  in  tissues  killed  by  the 
first  infection.  In  certain  infections,  as,  for  example,  in  many  forms  of 
pundent  processes,  the  tissues  may  contain,  even  at  an  early  stage,  two 
or  more  varieties  of  bacteria — a  mixed  infection  or  double  infection. 
The  associated  bacteria  can  persist  in  their  association  and  in  common 
excite  pathological  changes;  but  they  may  also  become  separated  fi'om  ;j 
each  other,  in  that  one  microorganism  gains  a  wider  distribution  than  | 
the  other. 

It  has  been  known  for  many  years  that  during  decomposition  poisonous  substances 
are  formed.     As  early  as  1852  Beck  observed  that  ammonia  hydrothionate,  which  oc- 
curs in  pus  and  putrid  ichor,  possessed  septic  properties  when  injected  into  animals. 
Pannm,  in  1863,  obtained  from  decomposing  material  a  putrid  -pouon,  that  is,  a  body 
not  ck'stroycd  by  boiling  and  evaporation,  wliich  possessed  an  action  similar  to  that 
of  snakc-iidi'-iin  "and  tlie  vegetable  alkaloids  and  caused  in  dogs  salivation,  dilatation  of 
the  iiupiU,  ilianiiu'a,  fever,  and  severe  prostration.      Yon  Bergmann  and  SchmUdehcrg 
obtained  IVoiu  decomposing  yeast  a  crystalline  body,  sepsin,  which  in  animals  produced 
the  symptoms  of  a  putrid  intoxication.     Senator,  Hiller,  and  Mikulicz  extracted  from 
decaying  tissue-masses  by  means  of  glycerin  a  substance  which  likewise  possessed  a 
septic  action.     Billroth  called  this  poisonous  substance  'putrefactive  zymoid.     Selmi  en-  i 
deavoicd  to  characterize  all  these  substances  more  minutely,  and  obtained  from  differ-  I 
ent  constituents  of  cadavers  extracts,  partly  soluble  in  ether,  partly  in  water,  which  he  j 
recouiii/.cd  as    fixed  bases    of  alkaloiiMike    character,   and    which  he   designated   as  j 
cadaveric  alkaloids  or  ptomains.     Cumticr,  Etard,  Zuelzer,  Sonnenschein,  Bechamp, 
l<clniii(dih(  !■(/,  Ihirridch,  r.  Xi  iirki.  Otto,  Ai///erer,  and  others  also  found  in  decomposing  | 
tissues  similar  cadaveric  alkaloids,  whicli  in  experiments  upon  animals  were  partly  in-  ; 
ert,  and  partly  toxic,  producing  in  the  latter  case  symptoms  of  poisoning  similar  to  i 
curare,  morphine,  and  atropine.     To  von  Isencki  (1876)  is  due  the  honor  o'f  being  the  ' 
first  to  obtain  a  cadaveric  alkaloid  in  its  pure  form  and  to  establish  its  formula;  this  '. 
was  accompli.shed  in  the  case  of  collidiu,  obtained  from  decomposing  glue  and  albumin,   i 
its  platinum  salt  crystallizing  in  tlat  needles.     Following  t\  JVeucki,  Etard,  Gaufier,   j 
and  Bauniann,  and  especially  Briefer,  have  studied  ptomains,  the  last  named  having  j 
obtained  a  large  number  of  them  in  a  pure  state  and  determined  their  physiological  ! 
action.     For   instance,  Brieger   obtained   from   fibrin  peptone  a  poison   (peptotoxiu)  ' 
which  in  animals  causes  symptoms  of  paralysis  and  ultimately  death.     From  decora-  i 
posing  horse-Hesh    he  extracted    three    substances  crystallizing  in  needles,   namely, 
neuridin,  neurin,  and  cholin,  the  second  of  wdiich  is  markedly  poisonous,  and,  like  ! 
muscarine,  causes  salivation,  disturbances  of  circulation  and  respiration,  contraction  of  '' 
tiw  pupils,  and  clonic  convulsions.     From  fish-flesli  he  obtained,  besides  neuridin,  three  ' 
other  poisonous  bodies:   ethylendiamin,  a  sulistance  similar  in  its  action  to  muscarine, 
and  a  .substance  called  gadinin.     From  decomposing  glue  and  cheese  he  obtained  tlie 
poison  neurin,  and  from  decomposed  yeast  dimetliylamin. 

The  majority  of  ptomains  are  not  found  in  fresh  tissues,  and  it  is  therefore  very 
prol)able  that  they  arc  derived  from  the  splitting  of  chemical  combinations  present  m. 
the  tissues.  Thus  it  is  prolxible  that  cholin  is  formed  from  the  splitting  of  lecithin, 
and  by  the  further  decomposition  of  cholin  the  ]ioison  neurin  is  formed.  Cholin  and 
neuridin  are,  acccjrding  to  Brieger,  demonstrable  even  in  the  fresh  human  brain. 

After  the  poisonous  nature  of  part  of  the  ptomains  had  been  made  knowTi  through 
the  researches  mentioned  above,  there  was  developed  the  hypothesis  that  the  toxic  symp- 
toms observed  in  infectious  diseases  could  be  entirely,  or  in  a  great  measure,  ascribed 


BACTERIAL    INFECTIOX.  39 

to  the  action  of  the  toxic  ptomains.  Through  the  investigations  of  recent  years 
iltiiiLV.  Ycrsin,  Buchncr,  Bricgcr.  C.  Fracnkcl,  P/eiffcr.  IChiiic/i.  Wasscninnin.  nndotliers) 
it  has  been  shown  tiiat  besides  the  iitomains  there  occur  specific  bacterial  poisons, 
wliich  are  characteristic  for  the  sjiven  bacterial  species.  Tliese  were  first  refjarded  as 
ac'iive  aliiuniin  boihes  and  were  called  toxalbumins.  Bricijer  and  Frumkci  \\o\i\  the 
\  ii'w  that  they  are  formed  by  the  action  of  bacteria  from  the  albumins  of  the  body 
jiiiccs.  Buchncr.  on  the  contrary,  believes  that  they  are  produced  by  the  bacterial  cell 
ii-ilf.  Investijiations  on  the  poisons  formed  in  diphtheria,  tetanus,  cholera,  typhoid 
li'Ncr.  pneumonia,  and  tuberculosis  have  shown  that  the  so-called  toxalbumins  are  not 
alliuniin  bodies,  and  liave  led  to  the  differentiation  of  different  ijoisonous  substances 
as  iriven  in  the  text  above. 

The  toxins,  in  the  strict  sense,  may  be  conii)areil,  according  to  their  orifjin,  with 
till'  enzymes  formed  by  the  body  cells  (pepsin,  tryi)sin,  ptyalin)  which  produce  hydro- 
lytic  splittinii.  On  the  other  luunl,  the  endotoxins  clinf,n"n<r  to  the  cells  may  be'com- 
paii'd  with  the  expressetl  juice  of  yeast  known  as  Zymase  (Buchncr).  which  isalile,  in 
the  same  way  as  the  living  protoplasm  of  the  yeast-cell,  to  excite  an  alcoholic  fermenta- 
tiiMi  in  fluids  containing  sugar.  Toxins  and  enzymes  are  mixed  with  albuminous 
suli-tances  which  up  to  the  present  time  have  not  been  separated  from  them.  This 
(■\|ilains  why  they  were  earlier  regarded  as  all)uminous  bodies.  Bric(/cr,  who  first 
characterized  the  toxic  substances  as  toxalbumins,  has  himself  prepared  toxins  that 
gave  no  albumin  reaction. 

According  to  the  views  of  Ehrlich,  only  those  substances  are  poisons  that  possess 
a  chemical  affinity  for  some  element  of  the  body  and  through  their  union  with  this 
cause  an  injurious  action  that  may  be  recognized  clinically  (toxophorous  affinity). 
A  toxin  or  haptin  is,  according  to  him,  a  poison  which  possesses  two  specific  atomic 
groups,  a  haptophore  group  which  permits  the  union  with  the  body  cells  throigh  the 
haptophorous  group  of  the  latter,  and  a  toxophore  group  which  exerts  the  poisonous  action. 
If  in  any  poi.son  the  specific  action  of  the  toxophore  group  is  lost,  while  the  haptophore 
group  remains,  there  arise  toxoids  or  non=poisonous  haptins  which  may  anchor 
I  themselves  to  the  body  cells  but  are  no  longer  ]3oisons.  Finally,  there  occur  also 
I  primary  bacterial  products  (in  diphtheria),  the  toxons  (lihrlich),  that  is,  poisons  which 
have  the  same  haptophore  group  as  toxins  but  a  less  acti\e  toxojjliore  group. 

Since  the  infraccUuIar  io.rins,  the  endotoxins  (typhoid  l)aoiili,  cholera  spirilla,  B. 
pyocyaneus.  pus  cocci),  are  stored  up  in  the  bodies  of  the  liacteria,  the  bacterial  cell- 
substance  is  the  most  active.  In  old  cultures  the  poisons  pass  over  into  the  fluid,  liut 
they  probably  no  longer  represent  the  primary  endotoxin,  but  a  modification  of  the  same. 

Cholera  spirilla,  typhoid  bacilli,  and  pneumococci  form  endotoxins,  which  on  the 
death  of  the  bacteria  are  in  part  set  free,  and  become  active  as  such,  or  act  in  a  modified 
form  at  the  same  time  with  the  bacterial  proteins. 

Anthrax  and  tubercle  bacilli  probably  form  no  true  toxins,  but  contain  poisons  of 
another  kind  whose  action  is  combined  with  that  of  the  bacterial  proteins. 

The  importance  and  the  course  of  an  infection  depend,  therefore,  upon  the  char- 
acter of  the  cells  possessing  receptors  for  the  given  toxin.  In  tetanus  it  is  the  nerve- 
cell;  in  diphtheria  and  tuberculosis  the  connective-tissue  cell.  Diphtheria  poison  does 
not  injure  the  skin  of  the  mouse,  while  the  one-hundredth  or  one-thousandth  part  of 
the  same  dose  will  produce  tissue-necrosis  in  the  guinea-pig  (Ehrlich). 

Aggressins:  When  bacteria  are  grown  in  the  pleural  or  peritoneal  cavities,  in 
pleural  or  peritoneal  exudates,  blood-serum,  or  even  in  distilled  water,  there  is  formed 
a  substance  which,  when  the  non-toxic  sterihzed  culture  fiuid  is  inoculated  at  the 
same  time  with  a  sublethal  dose  of  the  bacteria,  neutralizes  the  protective  powers  of 
the  body  and-permits  the  growth  of  the  bacteria.  The.se  sub.stances  have  been  called 
aggressins,  and  may  be  regarded  as  serving  the  bacterial  organism  in  the  same  way 
that  the  opsonins  protect  the  animal  body.     (Bail:  Arch.  f.  Hyg.,  1905.) 

Literature. 

(Bacterial  Iit/cciion  and  Intoxivaiion.) 

Bauingarten:  Der  gegenwiirtige  Stand  der  Bakteriologie.  Berlin,  klin.  Woch.,  1900. 
Bouchard:  Actions  des  produits  secretes  par  les  microbes  pathogdnes,  Paris,  1.S90; 

Thf'orie  de  I'infection.     X.   intern,   med.  Congr.   i.   Berlin,  1891;    Les  microbes 

])athog('nes,  Paris,  1892. 
Brieger:  Bakteriengifte.     Zeit.   f.  Hyg.,  xix.,  1895;  Diphtheric  u.  Tetanus.     Deut. 

mod.  Woch.,  1890;  Fleischvergiftung,  \h.,  1897. 
Buchner:   Ueber  Bakteriengifte,  Mi'mch.  med.  Woch.,  1893. 


40  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

Canon:    Bakteriologische  Blutuntersuchungen  an  den  Leichen.     Cent.  f.  a.  Path.,  xv., 

1904. 
Chantemesse:  Le  sol,  I'eau  et  I'air.     Traite  de  Path,  gen.,  II.,  Paris,  1896. 
Charrin:    ^'infection.     Traits  de  Path.  gen.  publ.  par  Bouchard,  ii.,  Paris,  1896. 
Debierre:   Les  maladies  infectieuses,  microbes,  ptomaines,   leucomaines,  Paris,  1888. 
Duclaux:   Ferments  et  maladies,  Paris,  1882;   Le  microbe  et  les  maladies,  Paris,  1886. 

rhi'-nomenes  generaux  de  la  vie  des  microbes.     Ann.  de  I'lnst.  Pasteur,  i.,  1887; 

Les  matieres  albuminoides,  ibid.,  v.,  1891;   Traite^  de  Mikrobiologie,  Paris,  1899. 
van  Ermengem:    Les  intoxications  alimentaires,  Bruxelles,  1895. 
Fischer:   Aetiologie  der  Fleischversiiftungen.     Z.  f.  Hyg.,  39  Bd.,  1902. 
Flexner:    Tlie  Pathology  of  Toxalbumins,  Baltimore,  1897. 
Fltigge:    Die  Mikroorganismen,  Leipzig,  1896. 

Forssmann:   Bakterologie  u.  BotuIi.smus.     Centralbl.  f.  Bakt..  xxix.,  1901. 
Gaflfky  ii.  Paak:    Wurst-  u.  Fleischvergiftung.     Arb.  a.  d.  Kais.  Gesundheitsamte, 

vi..   1890. 
Gamaleia:   Les  poisons  bacteriens,  Paris,  1892. 
Gautier:   Sur  les  alcaloides  derives  de  la  destruction  bacterienne  ou  physiologiques  des 

tissues  animaux,  ptomaines  et  leucomaines.  Paris,  1886. 
Germane:   Uebertragung  der  Infektion  durch  die  Luft.     Z.  f.  Hyg..  26  Bd.,  1897. 
Halban:   Kesorjit.  d.  Bakt.  bei  localer  Infection.     Jahrb.  d.  K.  Akad.,  \Yien,  1896. 
Hildebrand:   Eindringen  pathog.  Mikroorgani.smen  von  d.  Lunge  aus.     Beit.  v.  Zieg- 

Icr.  ii.,  1887. 
Hueppe:   Naturwissensch.  Einfiihrung  in  die  Bakteriologie,  Wiesbaden,  1896. 
Husemann:   Fleischvergiftung.     Encykl.     Jahrb.,    v.,    1895;      Ptomaine.     Eulenb. 

ihicykl..  xix.,  1898. 
Janowski:   Die  Ursachen  der  Eiterung  (Lit.).     Beitr.  v.  Ziegler.  xv.,  1894. 
V.  Kahlden:   Sepsis.     Eulenburg's  Realencyklop.,  xxii.,  1899  (Lit.). 
Koch:    rntcisuchungen  tiber  Wundinfectionskrankheiten,  Leipzig,  1887. 
Kruse:    Die  Kranklieitserregung,  Leipzig,  1896. 
Lenhartz:   Die  septischen  Erkrankungen,  Wien,  1902. 
Levy:   Sep.sinvergiftung.     Arch.  f.  exp.  Pathol..  34  Bd.,  1894. 

Ldffler:   Die  geschichtliche  Entwickchmg  der  Lehre  von  den  Bakterien.  Leipzig,  1887. 
Neisser:    Durcl-gaiigigk.  d.  Darniwund  f.  Bakterien.     Zeit.  f.  Hyg.,  xxii.,  1896  (Lit.). 
Notzel:    Infection   irraiuilirender  A\'unden.     Fartsch.,  xvi.,  1898. 
Oppenheimer:   Bakteriongifte.    Handb.  d.  pathol.  Mikroorganismen,  i.,  Jena,  1903. 
Panum:     Das  putride  Gift,  die  Bakterien,  die  putride  Infection  und  die  Septikamie. 

Viich.  Arch.,60Bd.,  1874. 
Pawlowsky:   Zur  Frage  der  Infection.     Zeit.  f.  Hyg..  33  Bd.,  1900. 
Petruschky :  Krankheitserreger  u.  Krankheitsbild."^  ^  Z.  f.  Hyg.,  36  Bd.,  1901. 
Rdmer:   Infection  vom  Conjunctivalsack  aus.     Zeit.  f.  Hyg.,  32  Bd.,  1899. 
Roth:    Durchlassigkeit  d.  Schleimhaute  u.  d.  iiuss.  Haut'fur  Bakterien.     Zeit.  f.  Hvg.. 

iv.,  1888. 
Roux  et  Vaillard:  Contr.  a  I'et.  du  tetanos.     Ann.  de  I'lnst.  Pasteur,  1893. 
Roux  et  Yersin:   Contr.  a  I'et.  de  la  diphtherie.      Ann.  de  I'lnst.  Pasteur,  1888  and 

1890. 
Runge :    Die  Krankheiten  der  ersten  Lebenstage,  Stuttgart,  1893. 
Schimmelbusch  u.  Ricker:   Bakterienresorption    frischer    Wunden.      Fortschr.    d. 

.Mc.l..  IS95. 
Simmonds:  Bakteriolog.  Blutuntersuchungen  an  der  Leiche.     Virch.  Arch.,  175  Bd. 

Treutlein:   Milzl)randinfektion.     Cent.  f.  allg.  Path..  1903. 
Vaughan  and  Novy:   The  Cellular  Toxins,  1902  (Lit.). 
Virchow:    Traumatismus  u.  Infection.     Virch.  Arch.,  162  Bd.,  1900. 
Wassermann:   Weson  der  Infektion.     Handb.  d.  pathol.  Organismen,  i.,  Jena,   1903. 
Woodhead:   Bacteria  and  their  Products,  London,  1891. 
.See  also  §  6  and  §  10. 


8  12.  Tlio  pathogenic   moulds  (^eumycetes)  and  the  budding  fungi 

Ix'loii^-,  as  do  llic  scliizoiiiycclcs,  to  tlio  iion-chiorophyllaceons  tliallo- 
I)liyt('s.  They  occui-  in  llie  liuiuuii  oroaiii.siii  in  the  form  of  jointed  or 
iion-joiiitod  and  sometimes  bi-aiicliiii<v  threads  or  hyphw,  and  short  oval 
cells,  the  so-called  couidia.  The  eumycetes  may  be  divided  into  the 
moulds,  llie  funjjns  of  thrush,  and  the  cutaneons  mould-fungi.  At  times 
tliey  form  fructification  organs  of  peculiar  structure.  The  siugie  cells 
arc  much  larger  than  those  of  tlie  scluzomycetes,  so  that  they  may  be 


:1 


INFECTION    BY   YEASTS    AND    AIOl  LDS.  41 

seen  with  lower  magnifyino:  power.  Outside  of  the  body  tlie  viouhls  de- 
veloj)  as  A'elvety  tilius  oi  ditferent  eolors,  on  the  surface  of  many  oi-j^anic 
substances  and  fluids,  from  the  carbon-compounds  and  salts  of  which  tliey 
deri\  e  their  nourishment.  The  //(((st-fiiiif/i  aic  fonnd  chiclly  in  Ihiids  con- 
tain in.u- sui^ar,  and  are  the  cansc  of  the  ah'oliolic  fci-mciitation  of  t lie  same. 

The  si)Oies  or  conidia,  Avliich  it'i)i'cs('nt  rt'sistant  r<'])ro(hictivc  cells, 
are  for  the<i,reater])art  formed  in  sj^'cial  orj;ans<>f  fructilication,  but  may 
also  be  developed  by  a  simple  process  of  constriction  of  the  ends  of  the 
hyplut^,  and  pass  into  the  air  from  the  surface  of  the  mould-film,  and 
may  be  widely  scattered  by  the  air-currents.  Likewise,  yeast-cells  may 
be  carried  about  in  the  air,  in  the  case  of  the  evaporation  of  a  fermenting 
lluid  and  the  conversion  of  its  residne  into  dust. 

The  ))toiil<ls  maif,  as  do  the  bacteria,  prodiK-e  poisonouH  mbstances  in  the 
nutria ir  media  in  which  thei/  muUiplti,  usually  lirst  outside  of  the  liumau 
body,  and  when  these  are  taken  in  Aviththe  food  symptoms  of  intoxica- 
tion are  produced.  For  example,  the  chronic  disease,  known  -as  pelhtf/ra 
or  maidism,  which  occurs  particularly  in  Italy,  Spain,  southwestern  por- 
tion of  France,  and  Eoumania,  and  is  chai'acterized  by  gastro-intestinal 
disturbances,  changes  in  the  skin,  spinal  and  cerebral  functional  distui'b- 
auces,  and  general  marasmus,  is,  according  to  the  view  of  many  Mriters, 
the  result  of  the  eating  of  corn  Miiich  has  been  Gpoiled  thi-ough  the 
growth  of  AsjiergiUus  fumigatuH  and  Jiaveseens  or  Poiieil/iinii  f/ldueion. 
According  to  Ceni  the  active  poisonous  substances  are  i)roduced  in  the 
spores  of  the  fungi. 

As  parasitic  agents  causing  disease  the  moulds  and  tlu^  yeasts  cause 
only  loeal  infections  characterized  by  tissue  degeneration  and  inllamma- 
tion. 

The  moulds  develop  in  regions  accessible  from  without,  in  the  skin, 
the  ear,  motith  cavitj^  lungs,  etc.  They  usually  occur  lirst  as  sapro- 
phytes in  cerumen,  necrotic  lung  tissue,  etc.,  but  they  may  also  ijene- 
trate  into  living  tissue. 

The  thmsh  fuji(/HS  occurs  chiefly  in  the  epithelium  of  the  njtper  laj^er 
of  the  mucosa  of  the  alimentai-y  tract,  but  often  i)euetrates  into  the  con- 
nective tissue  and  causes  inflammation.  Hoematogenous  metastasis  is 
rare. 

The  cutaneous  moulds  multi]>ly  in  the  epithelium  of  the  skin  and  cause 
inflammation  (favus,  herpes  tonsurans,  ])ityriasis  versicolor,  erythiasma). 

The  yeast  fungi  develop  most  fre(inently  in  the  stomach,  ]>articn!arly 
after  the  eating  of  fermenting  fruit  juices.  In  cases  of  glycosniia  they 
may  multiply  in  the  urinary  bhuhh'r  and  excite  there  a  fermentation. 
Within  the  tissues  they  develoi)  only  rarely,  and  cause  thei'c  local  intlam- 
mations  of  varjdng  character. 

Yeast-like  budding  fungi  occur  also  in  a  granulomatous  and  .sui)i)urativc  process 
afTecting  the  skin  and  internal  organs  (blastoniycetic  dermatitis,  blastomycosis,  sac- 
charomycosis,  coccidioidal  granuloma,  etc.).  the  majority  of  the  cases  have  oc- 
curred in  America.  The  para.sites  involved  cannot  at  present  he  definitely  classified. 
By  some  writers  (Ricketts)  they  are  believed  to  helong  to  the  genus  Oidium  {ouliomy- 
cosis).  Blastomycetes  are  supposed  to  Ijc  the  cause  of  a  peculiar  suppurative  disease 
in  horses. 

Literature. 

{Infection  by  Moulds  and  Yeasts.) 

Bestarelli:   Stand  der  reliagrafrage.     Cent.  f.  Bakt.,  xxxiv.,  1904. 

Buschka:    Ueber  Hefenm^kosen.     Klin.  Vortr.,  No.  18,  Leipzig,  1898. 

Busse;    Pathogene  liefen  und  Cctiimmeipilze.     Ergebn.  d.  allg.  Path.,  v.,  1900. 


42  THE    EXTRINSIC    CAUSES    OF    DISEASE. 

Cao:   Oidien  u.  ( tidiomvkosen.     Zschr.  f.  Hyg.,  34  Bd.,  1900  (Lit.). 

Ceni;   Aspprsjillus  fumiiratus.     Beitr.  v.  Ziegler,  xxxv.,  1904. 

Ceni  u.  Besta:    Asperjiillus  fumigatus  und  flavescens  u.  d.  Bez.  z.  Pellagra.     Cent.  f. 

allg.  I'alh.,  xiii..  1902. 
Dubi-euilh:   Les  moisissures  parasitaires  de  I'homme.     Arch,  de  med.  exp.,  1891  (Lit.). 
Leber:    Die  Entstehung  der  Entziindung,  Leipzig,  1891. 
liombroso:   Die  Lehre  von  der  Pellagra,  Berlin,  1898. 
Neusser:    Die  IVllagra,  Wien,  1887, 

Paltauf  uiiil  Heider:    Der  Bacillus  maidis  u.  s.  Bez.  z.  Pellagra.     Med.  Jahrb.,  1889. 
Pick:   .Stand  der  Derniatomykosenlehre.     Arch.  f.  Derm.,  xxix.,   1894. 
Podak:    Aspergillusmykosen.     Virch.  Arch.,  139  Bd.,  1895  (Lit.). 
Ricketts:    Oidionivcosis.     Journal  of  Med.  Research,  1901. 
Sanfelice:    Pathogene  Blastomyceten.     Zeit.  f.  Hyg.,  xxi.,  1896. 
Saxer:    Pn(Mimoiioinykosis  aspergillina,  Jena,  1900. 
Siebenmann:   Die  Schimmelmykosen  des  Ohres,  Wiesbaden,  1890. 
Sternberg:    Pathogene  Hefen.    Beitr.  v.  Ziegler,  xxxii.,  1902. 
Toulerton:   Pathogen.    Action  of  Blastomycetes.     Journ.  of  Path.,  vi,  1899. 
Tuczek:   Klin.  u.  anatom.  Studien  liber  Pellagra,  Berlin,  1893. 

§  13.  The  production  of  disease  by  animal  parasites  is  most  fre- 
quently broiiglit  about  by  the  iutroductiou  of  mature  parasites,  larvse, 
or  esgs  into  the  intestinal  tract  through  the  medium  of  the  food  and 
drink  or  by  unclean  fingers.  This  is  particularly  true  of  those  parasites 
whose  habitat  is  in  the  intestine  or  the  tissues  located  within  the  body ; 
such  parasites  are  accordingly  designated  as  Entozoa.  Parasites  living 
in  the  outer  tissues,  as  the  skin,  are  termed  Epizoa;  they  remain  either 
on  tlie  sui-face  of  the  skin  or  penetrate  into  the  same  from  without. 
The  passage  of  parasites  from  the  intestine  into  the  internal  tissues  and 
the  changes  thereby  produced  constitute  the  condition  which  is  usually 
called,  after  the  designation  first  used  by  Heller,  an  invasion-disease. 
The  animal  parasites  for  the •  greater  part  produce  only  local  changes, 
but  they  can  also  cause  symptoms  of  a  general  disease,  particularly  when 
the  ])arasites  increase  in  the  body  and  are  present  in  great  numbers  in 
the  1)1  ood  or  certain  tissues,  or  when  they  produce  toxic  substances. 

The  parasitic  protozoa  are  partly  harmless  parasites,  which  develop 
in  the  secretions  of  the  mucous  membranes  without  causing  pathological 
changes.  Other  forms,  on  the  contrary,  can  penetrate  into  the  living 
tissues,  increase  inside  of  cells,  and  give  rise  to  local  morbid  changes, 
characterized  chiefly  by  peculiar  new-formations  of  tissue  (coccidia-dis- 
ease  of  the  i-abbit's  liver,  epithelioma  contagiosum).  Certain  forms, 
wliicli  are  x)i'obably  to  be  classed  as  Sporozoa,  increase  in  the  blood,  as 
inhabitants  and  destroyers  of  the  red  blood  cells,  and  are  the  cause  of 
the  infe(;tioiis  disease  known  as  malaria.  Others  still  (trypauosomata) 
inhabit  the  bl()0(l-]>liisma.  It  is  not  impossible  that  other  infectious  dis- 
eases, for  exami)]e,  small-pox,  are  caused  by  parasites  belonging  to  the 
Protozoa. 

The  parasitic  worms  ( Neinafodes,  Ccstodes,  Trematodes)  occur  in  man, 
partly  in  the  adnll  and  fully  developed  sexual  state,  and  partly  in  the 
lai'val  state.  In  tlie  first  case  they  are  for  the  greater  part  intestinal 
I)afasiles,  which  obtain  nourishment  from  the  intestinal  contents,  rarely 
sucking  tiic  blood  from  tiu'  intestinal  mucosa.  Fully  developed  worms 
are  also  foimd  in  other  regions,  as  in  tlie  blood-  and  lymph-vessels,  bile  '■ 
passages,  lung,  ])elvis  of  the  kidney,  and  in  the  skin.  The  eggs  or  fully 
develoi)ed  larvae  i)roduced  in  the  body  by  parasitic  worms  are  either  cast 
out  with  llu*  dejecta  or,  througli  active  wandering  or  metastasis  through 
the  blood  or  lympli,  finally  reach  other  organs  of  the  body,  where  they 
pass  the  lii'st  stage  of  their  <levelo])nuMit .     Here  they  remain,  however. 


IXFECTIOX    BY    AXIMAL    PARASITES.  4o 

in  ;i  larval  condition,  and  do  not  roach  sexual  nuiturity.  The  larvic  are 
capable  of  further  development  only  when  they  have  been  taken  into  a 
new  host,  or  have  been  a,<;ain  eaten  by  the  same  host. 

The  worms  which  reacli  their  sexual  maturity  in  Ihc  human  body  arc 
taken  in  as  larvie  through  the  food  and  diink.  Their  lirst  stage  of  de- 
velopment is  passed  in  the  great  majority  of  cases  in  animals  whose  llesh 
is  nsed  for  food;  in  other  cases  in  certain  of  the  lower  animals  not  used 
as  food.  Others  develop  in  water  or  damp  earth  or  even  in  the  human 
intestine,  so  that  the  embryos  or  eggs,  which  pass  off  with  the  dejecta, 
develop  at  ouce  in  case  they  are  again  introduced  into  the  intestinal 
tract  of  man. 

The  worms  which  occur  in  man  only  in  the  larval  condition  (hydatids) 
develop  from  eggs  which  ha\e  come  from  sexually  uiature  worms,  which 
inhabit  diiferent  animals.  They  are  taken  into  the  intestinal  tract  usu- 
ally in  the  food  or  drink,  but  under  special  conditions  eggs  capable  of 
development  may  be  contained  in  the  dust  of  the  air,  and,  being  inhaled 
and  finally  reaching  the  intestinal  tract,  complete  the  first  stage  of  de- 
velopment. 

The  intestinal  parasites  for  the  greater  part  produce  only  slight  dis- 
jturbances,  though  they  luay  cause  mechanical  irritation  of  the  intestine. 
I  The  presence  of  blood-sucking  worms  iu  large  niimhers  (Anclii/Iosfotjia 
Iduodotale)  can  cause  anremia.  Some  also  produce  poison  (Botlnioccph- 
I  alun').  Those  parasites  which  enter  the  tissues  may  cause  in  their  \  icinity 
jmild  inllammation  and  proliferation  of  tissue,  which  may  ])i()duce  more 
{marked  clinical  symptoms  when  the  number  of  the  i)ai'asites  {irir/iina- 
I  hirrw)  iu  the  tissues  is  very  great.  Others  are  of  pathological  impor- 
i  tance,  in  that  they  reach  a  large  size  (ecJiinococcus  cysts)  and  thereby 
i  crowd  aside  and  compress  the  neighboring  structures. 
I  Otherwise  their  pathogenic  significance  depends  essentially  upon  tlieir 
j  location.  A  parasite  situated  in  the  muscles  or  subcutaneous  tissue  may 
I  cause  very  slight  symptoms,  while  one  in  the  eye,  medulla  oljlongata, 
'.  heart,  or  blood-vessels  may  cause  severe  disturbances,  and  under  certain 
conditions  death. 

The  parasitic  arthropoda  (Arachnida  and  Insects)  come  to  the  human 
body  partly  from  the  outer  world,  partly  from  infected  animals,  and 
partly  from  infected  human  beings.  They  belong  almost  wholly  to  the 
E])izua,  which  have  their  habitat  iu  and  upon  the  skin  and  accessible 
mucous  membranes  (lice,  bedbugs,  fleas,  mites)  or  only  occasionally  take 
llicir  nourishment  from  the  skin  (gnats,  gad-flies,  flies),  afewmnltiiily 
eitlier  in  the  skin  (itch-mite)  or  upon  its  surface  { lice).  Flies  and  gad- 
flics  occasionally  lay  their  eggs  upon  the  mucous  membranes  or  surfaces 
of  wounds,  and  from  the  eggs  so  laid  larvie  may  develop.  The  larva  of 
an  arachnoid  (Fentastoma  denticulatum)  is  alone  found  in  the  intei-nal 
(.1  uans.  In  so  far  as  these  parasites  penetrate  into  the  tissues,  they  cause 
ii  illation  and  inflammation;  the  bite  of  insects  that  suck  blood  is  also 
followed  by  an  inflammation  in  the  neighborhood  of  the  ]»uncturc. 

Attention  has  recently  been  directed  to  the  i)ossi])ility  that  nios- 
quitos,  stinging  flies,  gad-flies,  bed-bugs,  lice,  etc.,  may  be  Ihc  conveyers 
of  an  infection,  in  that  bacteria  or  protozoa  may  by  chance  Ix^  attached 
to  their  bodies,  or  that  in  the  act  of  sucking  blood  of  an  infected  man  or 
animal  they  may  take  up  into  their  bodies  either  bacteria  or  protozoa 
and  later  convey  them  to  other  individuals.  So  far  as  experience  goes, 
tlic  danger  of  such  conveyal  is  not  very  great  in  the  case  of  the  majority 
of  the  infectious  diseases,  since  the  bacteria  thus  taken  up  die  after  a 


44  THE    EXTRTXSIC    CAUSES    OF    DISEASE. 

time ;  yet  it  is  probable  that  such  conveyal  does  take  place,  as,  for  ex? 
ample,  in  plague,  infection  with  pus-cocci,  and  authrax.  Tliis  metho( 
of  couveyal  is  of  chief  importance  in  malaria,  in  that  the  j;?rtsmo(Zi(X  take] 
from  the  blood  of  infected  individuals  by  mosquitoes  (anopheles)  underg 
further  development  in  the  body  of  the  mosquito  and  produce  a  new  generation 
which  through  the  bite  of  the  mosquito  is  transferred  to  another  individual, 
that  the  si)read  of  malaria  is  accomplished  through  mosquitos.  SimilaB 
conditions  exist  also  in  the  case  of  the  tsetse-fly  disease  and  Texas  feve; 
of  cattle,  the  latter  being  conveyed  by  ticks.  Further,  it  is  claimed  bi 
Manson,  Sonsino,  and  others  that  the  infection  of  man  with  the  filaria  i 
also  brought  about  through  the  agency  of  mosquitos. 

Of  the  parasitic  protozoa  there  should  be  mentioned  also  the  Amoeba  dysenteria 
the  cause  of  one  form  of  dysentery  in  man;  the  Trypanosoma  evansi,  the  cause  c 
surra;  Tr.  brucei,  the  cause  of  the  tsetse-fly  disease  or  nagana;  Tr.  gambiense  th 
etiological  agent  in  human  trypanosomiasis  or  sleeping-sickness;  and  the  Trichomona 
as  a  probable  causal  agent  in  catarrhal  conditions  of  intestine  or  genito-urinary  trad 
Supposed  protozoan  parasites  have  also  been  described  as  the  causal  factors  of  small 
pox,  scarlatina,  tick-fever  in  man,  rabies,  syphilis,  tumors,  etc.,  but  convincing  proof 
are  not  yet  at  hand.  A  protozoal  origin  is  also  assumed  by  some  writers  for  yellow 
fever,  partly  because  of  the  fact  that  the  causal  agent  of  this  disease  is  conveyed  by  a 
mosquito,  Stegomyia  fasciata  {Reed  and  Carroll). . 

Literature. 

(Origin  of  Disease  through  Animal  Parasites.) 

Blanchard:   Parasites  animaux.     Path,  gen.,  ii.,  Paris,  1896. 

Braun:   Die  thierischen  Parasiten  des  Menschen,  Wiirzburg,  1893. 

Celli:    Die  Malaria,  Berlin,  1900. 

Grolgi:  Malariainfection.     Arch,  per  le  Sc.  med.,  x.,  1886,  and  xiii.,  1889;  Arch.ital.de 

Biol.,  ix.  and  xiv.,  1890;    Beitr.  v.  Ziegler,  iv.,  1889,  and  vii.,  1890;  Zeitschr.  f. 

Hyg.,  X.,  1891. 
Grassi:   13ie  Malaria,  Jena,  1901. 
Howard:   Mosc|uitos,  New  York,  1901. 

Huber:    Hil)liographie  der  klin.  Helminthologie,  Miinchen,  1891-1895. 
Laveran:   l)u  paludisme  et  de  son  hematozoaire,  Paris,   1891. 
Laveran  vi  Mesnil:   Trypanosomes  et  Trypanosomiasis,  Paris.  1904. 
Leuckart:   Die  thierischen  Parasiten  des  Menschen,  2  Aufl.,  1879-1897. 
Ltihe;    Ilrgebnisse  der  neueren  Sporozoenforschung.     Cent.  f.  Bakt.,  xxvii.  and  xxviii., 

Mannaberg:  Die  Malariaparasiten,  Wien,  1893;  Die  Malariakrankheiten,  Wien,  1899. 

Miihling:  IJebertragung  von  Krankheitserregern  durch  Wanzen  u.  Blutegel.  Cent, 
f.  Bakt.,  XXV.,  1899. 

Nuttal:  Die  Mosquito-Malariatheorie.  C.  f.  Bakt.,  xxv.  and  xxvi.,  1899;  die  Rollei 
der  Insecten,  Arachnoiden  u.  Myriapoden  als  Trager  bei  der  Verbreitung  von 
durch  Bakterien  u.  thier.  Parasiten  verursachten  Krankheiten.  Hygien.  Rund- 
schau, ix.,  1899,  ref.  Cent.  f.  Bakt.,  xxvi.,  1899. 

Reed:  I^tiology  of  Yellow  Fever.  Pan- Amer.  Cong.,  1901;  Amer.  Med.,  1901;  Med. 
lioc,  1901. 

Schneidemiihl:   Die  Protozoen  als  Krankheitserreger,  Leipzig,  1898. 

Uhlworm:   Contralbl.  f.  Bakt.  u.  Parasitenkimde,  1887-1900.'' 

II.  Congenital  and  Inheritable  Anlage  of  Disease. 

1.    Lnniunitij^   Fredi.sjmsition,   and  Idiosgnerasg. 

§  14.  Toward  the  injurious  agents  capable  of  producing  disease  differ- 
ent individuals  show  very  different  powers  of  resistance,  and  such  differ- 
ences ai-e  exhibited  particularly  in  the  case  of  the  infectious  diseases  audi 
many  poisons.  When  an  individual  is  not  susceptible  to  a  given  infec- 
tion or  poison,  the  property  thus  manifested  is  designated  as  immunity  i 
and  as  insusrrptihility  to  poison;  but  if  an  individual  is  easily  infected  by 
a  pathogenic  Tnicinxuganism,  we  assume  that  he  possesses  iC predisposition 


COXGKXITAL    AND    TXUKHTTAT^LF    DTSE ASFS.  45 

'  to  the  jiivoii  disease.     If  influences  of  any  kind  havinj,^  no  eflVct  on  ordi- 
!  nary  individuals  are  able  to  throw  certain   i)ers()ns  into  a  ])aIh<)lo<vi('al 
I  condition,  this  plienomenon is  explained   tiirini-h  tlir  assuniptidu  of  an 
extraordinary  sensitiveness,  an  idiosi/ncni.s;/. 

ImmKniti/  and  2)ir(lispo.sifi(»i   represent   the  opposite  behaviors  of  an 
organism  toward  external  injurious  ai;ents,  but  at   the  same  time  Ihey 
'  cannot  be  shari)ly  separated  from  each  other.      In   very  many  <'ascs  tiie 
immunity  is  not  absolute  but  ouly  relative,  so  that  the   individual   con- 
cerned may  be  nuule  ill  throui;h  a  ,i;iven  harmful  aj^ent,  for  example,  a 
'  pathogenic  microoruanism  or  a  poison,  wIumi  the  agent  acts  in  its  char- 
acteristic manner  and  strength.     On  the  other  hand,  the  i)redisposition 
I  to  a  disease  may  be  but  slight,  so  that   the  latter  occuis  only  under  es- 
)  pecial  conditions. 

i        An  absolidc  iinntiDtif//  or  insuscejyfibiJit)/  is  ])ossessed  by  man  against 

i  many  of  the  microorganisms  pathogenic  for  aninuils,  for  example,  the 

bacteria  of  swine  ])lague,  swine  erysijx'las,  and  sym^itomatic  anthrax, 

and  this  may  rest  upon  the  fact  that  the  character  of  his  tissue  and  tissue 

;  juices  does  not  admit  a  localization  and  multiplication  of  the  given  bac- 

I  t^ria,  or  that  the  poisons  produced  by  the  latter  are  not  i)oisonous  Un-  man. 

I        The  human  race  is  vert/  susceptMe  to  smallpox,  vaccinia,  measles,  and 

!  influenza,  so  that  the  great  majority  of  human  individuals  in  the  course 

I  of  life  acquire  these  diseases.     In  the  case  of  other  diseases,  as  scarlet 

I  fever,  pneumonia,  typhoid  fever,  diphtheria,  the  sii.srcjdibilitj/  srons  much 

lexH,  but  it  is  not  possible  to  determine  exactly  to  what  extent  the  great<'r 

rarity  of  these  diseases  is  dependent  upon  tlie  fact  that  the  individuals 

not  affected  are  not  exposed  to  the  infection. 

In  the  case  of  many  infectious  diseases,  there  is  a  greater  suscepti- 
bility shown  in  childhood  than  in  old  age ;  as,  for  example,  diphtheria, 
whooping-cough,  and  scarlet  fever.  Further,  there  are  also  variations 
in  the  degree  of  susceptibility  at  different  times,  as,  for  example,  an  in- 
dividual may  be  exposed  at  certain  times  to  measles  without  becoming 
infected,  while  at  other  times  under  similar  conditions  he  may  contract 
the  disease. 

In  the  case  of  many  pathogenic  organisms  there  appears  to  be  neces- 
sary for  the  entrance  of  infection  a  certain /ayo/'/»<7  condition  or  temporary 
increase  of  sttseeptihildy.  As  evidence  of  this  may  be  taken  the  fact  that 
in  the  human  alimentary  canal,  especially  in  the  mouth  and  throat, 
as  well  as  in  the  respiratory  tract,  pathogenic  organisms  (streptococci, 
staphylococci,  ])neumococci,  tubercle  bacilli)  may  be  ])resent  without  the 
occurrence  of  an  infection.  It  may  also  liapi)en  that  cholera  spirilla 
may  increase  abundantly  in  the  intestine  without  causing  marked  symp- 
toms. 

Such  occurrences  may  be  explained  in  part  by  a  decrease  or  loss  of 
virulence  on  the  part  of  such  bacteria,  but  this  explanation  cannot  be 
applied  to  all  cases.  In  many  instances  it  must  be  assumed  that  the 
harmlessness  of  the  bacteria  is  due  to  the  ability  of  the  tissues  to  hinder 
their  entrance  into  the  deeper  parts.  In  some  cases  this  may  depend 
upon  the  structure  and  organization  of  the  tissue,  in  other  cases  chemical 
substances  may  have  a  determining  intluence  (see  §20).  In  favor  ot  the 
first  assumption  lies  the  fact  that  tissue-lesions,  which  ])ermit  of  the 
entrance  of  bacteria,  bring  about  an  infection.  A  wound,  therefore, 
in  whatever  xcay  produced,  forms  a  Joeal  prrdi.s]>osition,  and  the  disease, 
in  such  cases,  bears  the  character  of  a  wound-infection.  Infections 
caused  by  pus-cocci,  tubercle  bacilli,  tetanus  bacilli,  glanders,  and  an- 
thrax bacilli  are  often  of  this  character. 


46  THE    IXTRIXSIC    CAUSES    OF    DISEASE. 

Other  causes  leading  to  an  increased  predisposition  to  infection  are 
less  easily  recognized.  It  appears  that  severe  chUling,  "takbtfi  of'coJd,^''  or 
hunf/fv  may  have  tliis  eliect ;  also  c/i<(it(/('.s  ui  the  tlafiues  due  to  pteeeding 
infections  or  non-infectiom  local  or  f/eneral  diseases  (see  §  11,  Secondary 
Infections).  In  tlie  case  of  intestinal  infections  (typhoid,  cholera),  gastro- 
intestincd  disturbances,  diminished  acidity  of  the  stomach  contents,  over- 
loading of  the  intestines,  retention  of  the  contents,  etc.,  play  an  impor- 
tant lole.  Xot  infreciuently  it  is  impossible  to  deterinine  what  causes 
liiue  favored  the  production  of  an  infection  at  a  gi^en  time. 

Special  predisposition  or  special  lessened  resistance  of  the  organ- 
ism is  also  not  infrequently  shown  to  other  injurious  agents  than  those 
of  infectious  nature.  Certain  individuals  are  less  able  than  others  to 
stand  external  high  temperatures,  particularly  if  at  the  same  time  bodily 
labor  is  performed.  Of  the  soldiers  on  a  march  only  a  fraction  may 
suffer  from  heat-stroke,  although  all  are  under  the  same  conditions.  The 
altitude  at  which  different  individuals,  during  mountain  ascents  and  bal- 
loon voyages,  become  sensible  of  the  deficiency  of  oxygen,  varies  greatly. 
The  effects  of  chloroform  anaesthesia  differ  greatly  in  different  individ- 
uals. Many  persons  become  exhausted  through  physical  or  mental  la- 
bor at  a  time  when  in  other  individuals,  under  like  conditions,  no  trace 
of  such  exhaustion  is  discoverable ;  and  such  influences  operating  daily 
upon  a  brain,  in  cases  of  especial  predisposition,  may  lead  to  diseased 
conditions. 

Occasionally  certain  individuals  show  a  sensitiveness  toward  particu- 
lar external  influences,  which  is  wholly  anomalous  to  that  usually  ob- 
served, so  that  symptoms  of  disease  may  be  caused  by  influences  which 
ordinarily  do  not  affect  the  majority  of  mankind.  Such  a  peculiar  sen- 
sitiveness is  designated  idiosyncrasy.  It  is  exhibited  particularly  in 
reference  to  certain  chemical  substances,  in  that  certain  articles  of  food 
or  drink  regarded  as  harmless  act  upon  such  persons  as  poisons.  The 
eating  of  fresh  fruit  or  sugar  or  salad  produces,  in  certain  individuals, 
nausea  and  vomiting.  Others  have  an  aversion  to  partaking  of  dishes 
prepared  from  liver  or  kidneys,  and  become  ill  if  they  overcome  this 
aversion  and  eat  these  foods.  Others  still,  after  eating  crawfish,  lobster, 
strawberries,  raspberries,  morels,  or  asparagus,  are  affected  with  urti- 
caria, a  disease  characterized  by  an  eruption  of  itching  wheals,  colic,  and 
vomiting.  Not  a  few  persons  are  unable  to  drink  boiled  milk  without 
un]il('asant  results  therefrom.  Alcohol,  even  in  very  small  doses,  may 
in  ct'itain  individuals  cause  marked  excitation,  or  narcosis,  or  remarka- 
ble disturbances  of  the  vaso-motor  system.  The  drinking  of  cocoa  may 
caus(;  cardialgia  and  dyspeptic  symptoms.  Doses  of  morphine  or  chloro- 
form, which  are  borne  by  the  majority  of  mankind  without  injury,  may 
cause  in  certain  individuals  severe  symptoms  or  even  death.  Some  in- 
dividuals show  a  high  degree  of  sensitiveness,  on  the  i)art  of  the  mucous 
meinl)ranes  of  the  respiratory  tract,  to  the  pollen  of  certain  grasses,  so 
that  during  the  time  of  the  hay-harvest  the  inhalation  of  the  pollen 
which  is  widespread  through  the  air  gives  rise  to  a  catarrhal  condition 
of  the  nose  and  conjunctiva,  often  of  the  larynx,  trachea,  and  bronchi, 
which  in  severe  cases  may  be  associated  with  asthma  and  fever.  These 
conditions  ai-e  known  as  hay-fever,  hay-asthma,  or  as  pollen-diseases. 
Acconliiig  to  the  investigations  of  Dunbar,  the  pollen  contains  a  substance 
that  may  be  extracted,  and,  when  injected  subcutaneously  into  those  dis- 
posed to  this  disease,  causes  the  characteristic  symptoms  of  intoxication. 
Disinfecting  fluids,  corrosive   sublimate  or   carbolic  acid,  in  solutions 


rEEDISPOSlTIOX    AXD    IDIOSYNCRASY.  47 

wiiicli  are  orcliiiarily  borne  without  discomfort,  may,  Mlieii  ai)i)lied  to 
the  skin  of  certain  individnals,  cause  not  only  local  distuibances  of  sen- 
sation and  intlanimation,  but  under  certain  conditions  may  excite  ;in 
eczema  that  spieads  over  a  lar<»e  part  of  the  body. 

On  what  the  i)eculiar  idiosyncrasy  in  individual  cases  depends  is  not 
clear.  In  many  cases  an  esi)ecial  excitability  of  the  neivous  system  or 
of  certain  parts  of  the  same  may  be  regarded  as  the  cause  of  the  ])hen()m- 
enon.  In  the  case  of  an  idiosyncrasy  toward  chemically  actixc  sid)- 
stances,  it  may  be  assumed  that  the  alfected  cell-protoi)lasm  contains 
atomic  groups  which  combine  with  the  i;iveii  substance. 

The  great  importance  of  the  part  playetl  by  natural  i)redisposition  and  immunity 
in  the  origin  of  infectious  diseases  has  not  only  been  made  evident  by  the  study  of  the 
spread  of  epidemics  among  men  and  animals,  but  has  received  also  abundant  confirma- 
!tion  by  mnnerous  experimental  investigations.  If,  for  example,  a  mixture  of  dilTerent 
bacteria  bo  injected  into  an  animal,  only  a  part  of  these  will  develop  and  produce  tis.sue- 
chamres:  the  others  die.  If  the  same  mixture  be  injected  into  an  animal  of  a  different 
species,  the  bacteria  which  develop  are  not  the  same  as  those  in  the  first  case.  Further, 
a  certain  form  of  bacteria,  which  when  inoculated  into  a  certain  species  of  mou.sc  in- 
variably causes  death,  may,  when  inoculated  into  another  mouse  of  dilTerent  species, 
be  without  efTect.  Mice  are  very  susceptible  to  anthrax,  rats  are  nearly  inunune.  The 
poison  of  the  so-called  septica^nia  of  rabbits  kills  with  ab.solute  certainty  rabbits  and 
mice;  guinea-pigs  and  rats  are  immune  to  it,  while  sparrows  and  pigeons  are  suscepti- 
ble. The  spirilla  of  relapsing  fever  may  be  .successfully  inoculated  only  into  apes. 
Gonorrhoea,  syphilis,  and  leprosy  cannot  be  successfully  inoculated  into  any  of  the 
lower  animals  with  the  exception  of  apes. 

In  the  case  of  a  natural  antitoxic  immunity  the  toxins  that  may  enter  the  organism 
may  remain  as  perfectly  harmless  material  in  the  body,  and  only  relatively  late  are 
split  up  in  the  process  of  metabolism.  In  such  ca.ses  the  avidity  between  the  toxin 
and  the  body  cells,  their  receptors  respectively,  may  be  entirely  wanting  or  very  slight. 
When  not  entirely  wanting,  an  increase  of  the  dose  may  produce  intoxication.  An 
immunity  against  small  doses  may  arise  through  the  anchoring  of  the  poison  (for  ex- 
ample, tetanus  poison)  to  tissue  elements  whose  changes  do  not  produce  symptoms  of 
disease;   or  antitoxins  may  be  present  which  render  the  toxins  inert. 

The  especial  diseases  to  which  the  new-horn  so  frequently  succumb  are,  aside  from 
the  conditions  acquired  during  intra-uterine  life,  dej:)endent  partly  upon  a  pathological 
weakness  of  the  entire  organism  (especially  in  case  of  premature  birth),  and  partly  upon 
the  surrounding  conditions.  Asphyxia,  which  is  of  such  frequent  occurrence,  may 
arise  either  as  the  result  of  bodily  weakness  or  of  pathological  influences  exerted  dur- 
ing delivery.  Infectious  diseases  may  be  acquired  through  the  stiunj)  of  the  cord  or 
through  the  accessible  mucous  membranes  and  respiratory  tract  during  birth.  Htenior- 
rhages  are  dependent  partly  upon  traumatic  influences  exerted  during  birth,  partly 
upon  di.sturbarces  of  circulation  and  upon  infections. 

Nurslings  and  als  j  older  children  are  more  susceptible  to  many  infections  than 
ladults;  particularly  so  in  the  case  of  whooping-cough,  diphtheria,  measles,  .scarlet 
fever,  and  tuberculosis.  In  the  intestine  of  nursing  infants,  bacilli,  tubercle  bacilli  in 
particular,  are  very  easily  taken  up  into  the  lymph-ve.ssels;  the  skin  of  infants  also 
ioffers  less  resistance  to  the  entrance  of  pus-cocci  than  that  of  older  individuals.  Young 
Mugs  may  be  easily  infected  with  anthrax  while  old  ones  cannot.  In  this  connection  it 
should  be  noted  that  the  -slight  susceptibility  or  the  inununity  of  many  adults  is  de- 
pi'iidcnt  upon  the  fact  that  they  owe  their  immunity  to  attacks  of  such  di.sea.ses  during 
childhood.  Further,  it  .should  be  remarked  that  children  are  more  exposed  to  certain 
infections,  for  instance,  tuberculosis,  than  are  adults. 

In  later  life  hemorrhages,  softening  of  the  brain,  cardiac  degenerations,  cancerous 
growths,  and  the  formation  of  gall-stones  are  of  especially  frequent  occurrence.  The 
disease  of  the  arteries  knowii  as  arteriosclerosis,  and  also  gout,  may  a|)pear  even  in  the 
late  years  of  middle  life.  The  predisposition  in  old  atje  to  certain  diseases  depends  in 
part  upon  degenerative  processes,  as.sociated  with  premature  senility  of  the  tissues:  in 
part  also  upon  the  fact  that  certain  infl  ences,  which  the  years  bring  with  them,  grad- 
ually accumulate,  so  that  finally  the  changes  which  they  produce  become  .so  i)rominent 
that  they  lead  to  functional  disturliances,  and  thereby  to  recognizable  morbid  condi- 
tions. Moreover,  it  is  to  be  remarked  that  many  pathological  .symptoms  of  old  ape 
are  .secondary  di.sea.ses,  which  become  api^arent  only  after  other  tissue-changes  have 
reached  a  certain  degree.  For  example,  .senile  luemorrhages,  senile  gangrene,  degenera- 
tions of  the  brain  and  heart  are  dependent  upon  disease-processes  occurring  in  the 
arteries. 


48  THE    IXTRINSTC    CAUSES    OF    DISEASE. 

The  predisposition  of  the  sexes  to  certain  diseases  depends,  in  the  first  place,  upon 
the  especial  structure  and  function  of  the  sexual  apparatus.  The  conditions  of  preg- 
nancy and  the  puerperium  otier  an  especially  favorable  field  for  many  diseases,  as,  for 
example,  for  infection  through  wounds.  Moreover,  different  relations  of  the  sexes  to 
many  diseases  may  be  explained  by  differences  in  the  modes  of  labor  and  in  the  habits 
of  living  of  the  two  sexes. 

Differences  of  predisposition  of  different  races  are  shown  particularly  in  regard  to 
malaria  and  dysenterv,  toward  which  the  negro  in  general  shows  less  susceptibility 
than  the  European.  'Malarial  parasites  may  be  present  in  the  blood  of  the  former 
without  giving  rise  to  symptoms  of  disease. 

Literature. 

(Predisposition  and  Immunity.) 

Bourcy:   PrcMisposition  et  immunite.     Pathol,  gen.,  i.,  Paris,  1895. 

Charcot:    Legons  sur  les  maladies  des  vieillards,  18G8. 

Dunbar:    Zur  Ursache  u.  Heilung  des  Heufiebers,  Munchen,  1903;    D.  med.  Woch., 

]9{)3. 
Ehrlich:  Experimentelle  Untersuchungen  iiber  Immunitat.    Deut.  med.  Wochenschr., 

1891. 
Emmerich:    Die  Ursachen  der  Immunitat.     Arch.  f.  Hyg.,  xii.,  1891. 
d'Espine  ct  Picot:   Manuel  pratique  des  maladies  de  I'enfance,  Paris,  1889. 
Galli-Valerio:  Immunita  e  resiatenza  alle  malattie.  Mil.,  1897. 
Goenner:    Heufieber.     Correspbl.  f.  Schweizer  Aerzte,  1897. 
von  Hansemann:  Die   anat.  Grundlage  d.  Disposition.    Deutsche  Klinik,  i.,  Berlin, 

1903. 
Henoch.:   A'orlesungen  iiber  Kinderkrankheiten,  Berlin,  1890. 

Hirsch:    Handbuch  der  historisch-geograi)liischen  Pathologic,  Berlin,  1881-1886. 
Hueppe:    Naturwissensch.  Einflihrung  in  die  Bakteriologie,  Wiesbaden,  1896. 
Jousset:   Traite  de  racclimatement  et  de  Tacclimatation,  Paris,  1884. 
Lode:    Beeinflussung  d.  Disposit.  z.  Infect,  durch  Warmeentziehung.     Arch.  f.  Hyg., 

28  Bd.,  1896. 
Lubarsch:   Untersuch.  iib.  d.  Ursachen  d.  angebor.  u.  erworbenen  Immunitat,  Berlin, 

1891;    Zur  Lehre  von  den  Geschwiilsten    u.  Infectionskrankheiten,  Wiesbaden, 

1899. 
Mag-gelsen:    I'eber  die  Abhangigkeit  der  Krankheiten  von  der  Witterung,  Leipzig, 

1S90. 
Marfan:   Le  surmenage.     Pathol,  gen.  de  Bouchard,  i.,  Paris,  1895. 
Martius:  Pathogenese  innerer  Krankheiten,  Leipzig,]  899  and  1900;  Krankheitsursache 

u.  Krankheitsanlage.     Verb,  der  Dtsch.  Ges.  d.  Xaturforscher,  Leipzig,  1898. 
Mtiller:    Die  Krankheiten  d.  weibl.  Korpers  in  ihren  Bezieh.  z.  d.   Geschlechtsfunc- 

tionen,  1888. 
Riess:    Heufieber.     Realencyklop.,  1896  (Lit.). 
Runge:    Die  Krankheiten  der  ersten  Lebenstage,  Stuttgart,  1893. 
Stockvis:    Vergleichende  Rassenpathologie  und  Widerstandsfahigkeit  des  Europaers 

in  tkm  Tropen.     Verb.  d.  X.  internat.  med.  Congr.  i.  Berlin,  1891. 
Zeehuisen:   Ueber  Immunitat  und  Idiosynkrasie.     Arch.  f.  exp.  Path.,  35  Bd.,  1895. 

2.    Inlieritahle  Diseases  Arisiiifj  from.  Congenital  Fatliotogieal  Anlage. 

§  15.    Among  the  morbid  conditions  arising  from  congenital  aniage, 

and  which  either  appear  spoutaueously  or  are  developed  through  any 
external  iniluence  whatsoever,  there  may  be  distinguished  different 
groups;  namely,  one  in  which  the  body  as  a  whole — the  constitution — is 
involved;  another  in  Mhich  only  a  part  of  the  body  as  a  system  or  an 
organ  is  affected;  and,  finally,  a  third  in  wliich  only  a  part  of  an  organ 
presents  functional  or  anatomical  changes  of  a  pathological  nature.  It 
must  be  noted  that  there  is  no  sharp  dividing  line  between  these  groups, 
inasmuch  as  local  pathological  changes  may  be  associated  with  constitu- 
tional conditions.  Further,  it  is  often  very  difficult  or  impossible  to  de- 
tennine  exactly  what  part  the  aniage  and  what  part  extrinsic  causes  have 


TATIIOLOGICAL    CONDITIONS    DUE   TO    I.\TI{I  XSIC    CAI^SES.   49 

taken  in  the  prodnction  of  sncli  ])alh()looie;il  conditions,  innsnincli  as  the 
force  of  the  external  inllnence  which  lias  called  the  patholoiiical  process 
into  activity  cannot  be  estimated  with  certainty. 

Among  the  constitutional  diseases  arising  from  intrinsic  causes 
are  to  he  mentioned,  tirst,  the  development  of  dwarfs  and  giants,  dis- 
turbances of  growth,  the  tirst  of  which  is  marked  by  an  nnder-develoj)- 
ment  of  all  the  ])aits  of  the  body,  both  of  the  skeleton  and  the  soft 
parts,  while  the  second  is  characterized  by  a  growth  e.\«'eeding  that  of 
the  ordinary  individual.  It  cannot  be  doubted  that  both  dwarf  and 
giant  growths  are  often  purely  dependent  upon  a  congenital  anlage; 
but  the  same  effects  can  be  produced,  at  least  in  so  far  as  the  iu- 
hibitiou  of  growth  is  concerned,  by  harmful  intlnences  exerted  dur- 
ing the  period  of  development  and  growth.  It  cannot  always  be  told 
with  certainty  whether  an  abnormal  bodily  growth  is  depemlent  U])on 
a  congenital  anlage  or  upon  pathological  intiuences  during  the  pei'iod 
of  growth,  as,  for  example,  defective  develoi)ment  or  disease  of  the 
thyroid  gland. 

The  same  difficulty  is  presented  iu  cases  in  w'hich  the  body  has  at- 
lained  full  development  of  stature,  but  manifests  a  general  feebleness  of 
onstitution,  as  shown  by  its  inability  to  withstaiul  a  gieat  vaiiety  of 
external  intiuences.  Such  condition  may  arise  either  fnmi  congenital 
iefective  and  weak  anlage  or  from  harmful  intiuences  which  have 
ittacked  the  developing  body  during  intra-  or  extra-uteiine  life; 
3r  further,  congenital  weak  anlage  and  external  weakening  intlu- 
mces  uuiy  have  affected  the  development  of  the  individual  in  au  equal 
neasure. 

A  further  constitutional  peculiarity,  w^hicli  is  founded  upon  a  spe- 
cial congenital  anlage,  is  corpulence  (obesity,  adlposUas,  lipomatosis  uni- 
versalis), a  condition  in  which  fat  is  deposited  in  au  excessive  amount, 
3ither  in  the  tissues  normally  containing  fat,  or  further,  in  regions  which 
lormally  contain  no  fat,  as,  for  examx)le,  beneath  the  endocardium  or 
)etween  the  muscles.  The  increased  deposit  of  fat  is  ultimately  to  be 
eferred  to  a  disproportion  between  fat-production  or  fat-supidy  and  fat- 
•onsumption,  the  pathological  increase  of  fat  being  at  one  tinu^  depend- 
■nt  upon  au  abnormal  increase  of  fat-production,  at  anothei-  on  a  de- 
if-nse  of  fat-consumption.  Daily  experience  teaches  that  the  enei-gy 
\  iih  which  metabolism  goes  on  in  the  body  differs  gi-eatly,  and  changes 
ilso  at  the  different  periods  of  life,  so  that  the  nonnal  amount  of  nour- 
>hmeut  tends  at  one  time  to  fatten,  at  another  time  does  not. 

In  the  pathological  condition  termed  obesitj^  which  in  part  rests 
ipou  a  congenital  tendency,  the  energy  of  the  ])roto]»lasmic  foices  of 
lestructive  metamorphosis  is  weakened,  so  that  an  abnormal  amount  of 
at  is  deposited,  even  when  only  a  moderate  or  even  a  decreased  amount 
•f  nutritive  material  is  supplied  to  the  tissue. 

Gout,  like  obesity,  is  also  a  constitutional  disease,  which  is  chiefly 
lependent  upon  a  congenital  anlage  aiul  is  produced  essentially  by  in- 
rinsic  causes.  The  exact  nature  of  the  disease  is  not  yet  known.  It  is 
haiacterized  by  deposits  of  uric  acid  in  the  tissues.  According  to  (Jar- 
o(l  and  Ebstein,  the  acute  attacks  of  gout  are  caused  by  an  accumida- 
ion  of  uric  acid  which  has  its  oiigin  either  in  the  kidm-ys  oi-  in  local 
onditions.  On  the  other  hand  Pfi-iffer  holds  that  the  essential  feature 
f  the  gouty  tendency  consists  in  the  fact  that  the  uric  acid  is  i)rodnced 
n  a  form  which  is  soluble  oidy  with  dihicultv.  Accoiding  to  vou 
4 


50  THE    INTRINSIC    CAUSES    OF    DISEASE. 

Noordeii,  the  formation  and  deposit  of  uric  acid  is  only  a  secondary- 
process,  which  is  induced  by  the  presence  of  a  certain  ferment  having 
only  a  local  actiou,  and  is  consequently  not  dependent  upon  the  amount 
or  character  of  the  uric  acid  formed  in  other  parts  of  the  body. 

Pathological  changes  arising  in  single  systems  and  organs  from 
congenital  aniage  may  occur  in  any  part  of  the  body,  and  may  involve 
an  entire  system  or  organ,  or  only  a  part  of  one. 

In  the  skeleton  thei-e  may  occur  abnormal  development  of  single 
parts,  as,  for  example,  an  abnormal  smallness  of  the  extremities  (micro- 
melia)  or  of  the  head  (microcephalus)  in  contrast  to  the  size  of  the 
trunk;  an  abnormal  over-development  of  a  bone  or  group  of  bones 
(macrocephalus,  macrodactylism,  giant  growth  of  a  finger,  entire  foot, 
or  of  an  extremity) ;  malformations  of  the  extremities  (cleft-hand,  cleft- 
foot,  etc.).  Occasionally  supernumerary  bones,  as  carpal  bones  or 
phalanges,  may  develop,  giving  rise  to  supernumerary  fingers.  Fur- 
ther, there  may  be  developed  atypical  formations,  such  as  bony  out- 
growths (exostoses,  hyperostoses),  which  may  extend  over  the  skeleton 
to  a  greater  or  less  extent,  originating  either  spontaneously  or  following 
some  traumatism. 

In  the  muscular  system  there  occur  particularly  pathological  bony 
formations,  eithei-  single  or  multiple  (myositis  ossificans),  which,  in  the 
period  of  childhood,  occasionally  lead  to  a  progressive  stiffness  of  the 
muscles,  through  the  transformation  of  muscle  into  bony  plates. 

In  the  vascular  system  there  occur  either  gross  anatomical  changes, 
such  as  abnormal  branching  of  the  arteries,  pathological  develoi^ment 
of  the  heart,  or  finer  changes,  which  reveal  themselves  through  some 
abnormal  action  on  the  part  of  the  circulatory  apparatus  or  through  a 
tendency  to  hiiemorrhages  (Jicemoj)hiUa)  which  take  place  spontaneously, 
that  is,  without  our  being  able  to  demonstrate  the  actiou  of  some  in- 
jurious influence  upon  the  heart  or  blood-vessels. 

During  the  development  of  the  central  nervous  system  there  may 
occur  primary  disturbances,  which  in  part  may  manifest  themselves  only 
through  some  pathoJogical  disturbance  of  function  or  some  special  2iy('dis- 
j)osition  to  disease,  while  others  are  distinguished  by  gross  anatomical 
changes,  such  as  abnormal  smallness  of  the  brain  (micrencephalon)  or  of 
the  spinal  cord  (micromyelia),  defective  develoj)ment  or  absence  of  par- 
ticular ])arts  (see  chapter  on  malformations),  misplacement  of  the  gray 
mattei-  (heterotopia  of  the  gray  substance),  abnormal  formation  of  cavi- 
ties (syringomyelia),  or  abnormal  formations  of  neuroglia.  These  dis- 
turbances may  involve  the  functions  of  the  sensory  organs  and  the  motor 
centres,  and  even  to  a  greater  extent  the  psychical  processes.  The  mor- 
bid conditions  known  as  idiocy,  epilepsy,  periodic  and  circular  insanity, 
hysteria,  neurasthenia,  as  well  as  paralysis,  mania,  melancholia,  and 
dementia,  may  have  their  origin  in  a  congenital  predisposition.  Ee- 
ccntly  the  tendency  to  crime  has  also  been  ascribed  to  a  congenital  pre- 
disposition, and  Lombroso,  in  particular,  has  endeavored  to  prove  tiiat 
the  man  who  lives  only  through  crime  and  for  crime,  the  Homo  delin- 
quens,  is  a  congenital  criminal— that  is,  a  man  who  suffers  from  bodily 
and  mental  abnormalities,  who  possesses  other  physical  and  psychical 
chaiacters  than  the  normal  man  or  even  than  one  who  is  simply  men- 
ially nn])alanced,  in  that  he  presents  the  symptoms  of  a  form  of  degener- 
ation tiMiding  in  a  well-defined  direction.  According  to  Lombroso,  a 
subnormal  development  of  the  anterior  half  of  the  cranium,  associated 
with  a  corresponding  lack  of  development  of  the  anterior  portion  of  the 


PATHOLOGICAL    COXUITIOXS    Dl  E    TO    IXTHIXSIC    CAfSES.     51 

•erebrum,  in  connection  witli  an  over-developnuMit  of  tlio  ])()sterior  por- 
iou,  prodnccs  a  feebler  development  of  the  intellii;ence  and  of  the  moral 
ense,  and  fa\ors  a  stron.uiy  developed  instinct-life.     Benedikt  even  j,M)es 

0  far  as  to  maintain  that  the  criminal  possesses  a  peculiar  confionration 
•f  the  cerebral  convolutions,  similar  in  tyi>e  to  those  of  beasts  of  i)rey. 

The  views  of  Lombroso  and  IJenedikt  have  nu't  with  much  opposi- 
ion,  and  have  been  attacked  as  incorrect.  There  can  be  no  doubt  that 
here  does  not  exist  a  degenerate  species  of  the  human  i-ace,  which  is 
liaracterized  by  such  anatomical  peculiarities  as  to  make  it  possible  for 
IS  to  distinguish  a  class  of  Ro)iio  dcliiiqiiois  from  that  of  Homo  mjyiens. 
Ul  the  somatic  peculiarities  regarded  as  characteristic  of  the  criminal 
ype — as,  for  example,  the  beast -of -prey  type  of  cerebral  convolutions, 
lightly  developed  frontal  brain,  receding  forehead,  massiveness  of  the 
ower  jaw,  prognathia,  asymmetry  of  the  ci-anium,  maiked  i)rominence 
f  the  arcus  superficialis  and  arcus  frontalis,  pathological  conformations 
|f  the  skull,  etc. —while  relatively  frequent  in  criminals,  are  also  far 
rom  being  infrequent  in  normal  men.  On  the  other  hand,  it  is  not  to 
•e  doubted  that  the  tendency  to  crime  is  very  frequently  dependent  upon 
,  congenital  predisposition  having  its  seat  in  some  special  organization 
f  the  central  nervous  system.  In  this  respect  the  criminal  resembles 
he  insane  individual;  further,  mental  diseases— for  example,  epilepsy 
jnd  hysteiia — are  often  observed  in  criminals. 

1  Pathological  cerebral  fnnctioHS  may  develop  iirimarily  in  individuals 
•ossessing  such  morbid  predispositions— that  is,  Avitlutut  external  intlu- 
uces  playing  any  part  in  the  production  of  the  disturbance,  so  that  the 
person  concerned  may  manifest  pathological  disturbances  of  cerebral 
junctions  without  the  concurrence  of  any  external  injury,  either  during 
[lie  period  of  development  and  growth  or  later.  On  tlie  other  hand,  iu 
jther  cases,  external  influences — such  as  mental  work,  sorrow,  care, 
sychical  irritation,  disease,  etc.— are  the  causes  which  give  rise  to  the 
articular  illness — that  is,  to  the  occurrence  of  pathological  brain  or 
piual-cord  functions.  In  these  cases  the  inherited  tendency  consists 
uly  in  an  abnormal  weakness,  a  predisposition  to  disease  of  the  central 
ervous  system,  so  that  insignificant  influences  which  would  produce  no 
^cognizable  effects  upon  a  normal  individual  are  sufficient  to  excite  the 
lorbid  phenomena.  Since  many  influences,  as  diseases,  infections, 
sychical  irritations,  are  adequate  under  certain  conditions  to  produce 
lental  diseases  in  individuals  who  must  be  regarded  as  normal,  it  is 
lear  that  in  many  instances  it  is  difficult  and  often  im])ossible  to  deter- 
liue  what  part  the  intrinsic  causes — the  iidierited  ])r('(lisposition — and 
hat  irdvt  the  extrinsic  causes  have  had  in  the  production  of  a  disease 
f  the  central  nervous  system. 

In  the  case  of  the  peripheral  nerves,  it  is  especially  their  connective- 
ssue  elements  which  often  take  on  a  pathological  activity  of  growth 
nder  the  influence  of  inti'insic  causes.  This  activity  may  manifest  it- 
ilf  partly  in  the  form  of  diffuse  thickenings  (fibromatosis  of  the  nerves), 
'hich  ai-e  situated  either  along  the  course  of  those  neives  large  enough 

be  dissected  with  the  knife  or  along  the  finer  nerves,  often  in  large 
umbers  thiough  the  entire  nei'vous  system,  and  occasionally  inxolving 
le  entire  territory  of  the  peripheral  nei'ves,  the  skin  being  most  fre- 
uently  affected  (multiple  fibromata  of  the  skin).  In  individual  cases 
le  fibromatosis  of  the  nerves  is  associated  with  an  inci-ease  in  the  num- 
er  of  nerve-fibres,  so  that  within  a  given  area  of  neiV(vdistribution 
lere  will  be  found  a  great  increase  of  nerve-fibres,  thickened  through  a 


52  THE    IXTRIXSIC    CAUSES    OF    DISEASE. 

pathological  increase  of  the  eudoneurinm  and  for  the  greater  part  twi,ste( 
and  wound  into  serpentine  foinis  (cirsoid  neuroma,  plexiforni  neuroma). 

Among  the  congenital  pathological  conditions  of  the  visual  appa= 
ratus  are  to  ht^  mentioned  in  pai'ticular  dyschromatopsia  and  acliroma 
topsia,  congenital  partial  or  total  color-blindness,  which  are  frequently, 
spoken  of  as  Daltonism,  and  are  characterized  by  a  want  of  perception 
for  certain  colors  (most  frequently  for  red  and  green)  or  for  all  the! 
colors.  In  this  same  category  belongs  further  the  typical  pigment  degen 
eratiou  of  the  retina,  in  which  there  occurs  a  peculiar  spotted,  blact 
pigmentation  of  the  retina,  associated  with  a  diminution  of  centraj 
sharpness  of  vision  and  light-perception,  with  a  narrowing  of  the  visua; 
field.  Finally,  certain  forms  of  myopia,  also  albinism  (absence  of  pig- 
ment in  the  choroid),  the  latter  condition  also  involving  the  structure.^ 
of  the  skin,  are  to  be  considered  in  this  connection. 

Of  intrinsic  conditions  of  the  auditory  apparatus  deaf -mutism  is  oi 
chief  importance;  this  condition,  in  part  at  least,  is  dependent  upon  ; 
primary  disturbance  of  development.  Further,  certain  malformatiou> 
of  the  external  ear  fall  into  this  class. 

In  the  skin  and  subcutaneous  connective  tissue  new-growths  maj 
develop  from  congenital  anlage,  consisting  of  proliferations,  sometimes 
of  connective  tissue,  at  other  times  of  epithelium.  They  often  involvt 
particular  parts  of  the  skin,  as  the  cutaneous  nerves,  blood-vessels, 
lymph-vessels,  or  the  adipose  tissue.  When  occurring  as  extensivt 
thickenings  of  the  skin  and  subcutaneous  tissue,  they  constitute  tht 
foundations  of  the  conditions  known  as  tibromatous,  neuromatous, 
hsemangiomatous,  lymphangiomatous,  and  lipomatous  elephantiasis.  As 
circumscribed  growths  they  are  known  as  birth-marks,  fleshy  moles, 
lentigines,  freckles,  and  tumors  of  the  blood-  and  lymph -vessels.  The 
epithelial  hypertrophies  give  rise  to  those  conditions  designated  as  fish 
scale  disease  or  ichthyosis,  ichthyotic  warts,  and  cutaneous  horns. 

In  addition  to  the  pathological  conditions  which  have  been  mentioned, 
there  are  also  malformations  of  the  body  (see  chapter  on  malforma 
tions)  or  also  of  internal  organs  which  must  be  regarded  as  primary— 
i.e.,  which  are  not  j^roduced  by  injurious  influences  exerted  upon  thi 
developing  foetus.  Finally,  many  forms  of  tumors  (see  chapter  or 
tumors)  are  to  be  placed  in  this  class,  particularly  those  which  are  founci 
to  be  already  developed  at  birth  or  which  develop  during  childhood. 

Literature. 

(Diseases  Arlsbig from  J)ifriiisic  Causes.) 

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lieiten,  Wien,  1892. 
Baer:  Dor  Verbrecher  in  anthropologischer  Beziehuna^,  Stuttgart,  1893. 
Benedikt:  Anat.  Studien  au  Verbrechergebirnen,  Wien,  1879;   Cent.  f.  d.  med.  Wiss. ' 

ISHO. 
Charcot:  Maladies    des  vieillards,  gouttes  et  rhumatisme.     (Euv.  compl.,  vii.,  Paris' 

1890. 
Cohn:  Studien  ilber  die  angeb.  Farbcnblindheit,  Breslau,  1879. 

Crocq:   I/unite  de  la  diathese  et  I'heredite  morhide.     liev.  de  med.,  1893.  i 

Ebstein:    Die  Fottleibigkeit,   Wiesl)ad('n,   1882;   Natur  uud   Behandlung  der  Gicht 

Wiesbaden,  1882;  Beitr.  z.  Lehre  von  der  harnsauren  Diathese,  Wiesbaden,  1891 

Die  Steilung  der  Fettlcibi«rkeit,  der  Gicht  und  der  Zuclierkrankheit  im  nosolog 

System.     Deutseli.  med.  Wocii.,  1898. 
Fere:  Nervenkrankhciiteu  nnd  ihre  Vererbung,  Berlin,  1896. 
Le  Gendre:  L'liercdite.     Pathol.  g<>n.  publ.  par  Bouchard,  i.,  Paris.  1895. 


THE    TXIlEHlTAXrE    OF    DISEASE.  53 

rrassmann:  Erblichkeit  der  Psycliosen.     Zoitschr.  f.  Psych.,  ."i'i  Bd.,  189r). 

laeckel:  Anthropogeuie,  1891. 

tiscli:    Die    Fettleibigkeit,  Stuttgart,   1888,  aud    Euleiiburg's    Ut-iilencyklop.,  Art. 

;       Fettsucht,  1895. 

Colisch:  Wcseu  und  Beliandlung  der  uratischen  Diathese,  Stuttgart,  189;). 

toiler:  Erblichkeitsstatistik  der  Geisteskrankheiten.     Arch.  f.  Psych.,  27  Bd.,  1895. 

Curella:  Ccsare  Lombroso  und  die  Naturgeschichte  des  Verbrechers,  Hamburg,  1893. 

iee:   De  I'obesite,  Paris,  1886. 

.ocher-Wild.  Ueber  Familienanlage  luid  Erblichkeit,  Zurich,  1874. 

.ombroso:  Der  Verbreclier,  i.-iii.  (mit  Biidcratias),  llainhurg,  1891-1895. 

.ombroso  u.  Ferrero:  Das  "Weib  als  Verbrcchcrin  und  Prostituirte,  Iluiuburg,  1894. 

linkowski:  Die  Gicht,  Wien,  190:^. 

'-.  Noorden:  Pathologie  (h^s  StofTwcchsels  (Fettsucht,  Giclit),  Jena,  189:5. 

•feitfer:    Das  Wesen  der  Gicht,  AVicsbaden,  1891. 

chaefifer:  Fotale  Oiirformen  bei  Ervvaciisenen.     Arcli.  f.  Antliropol.,  xxi.,   1893. 

ernoff:  Die  Lehre  Lombroso's.     Biol.  Centralbl.,  xvi.,   1896. 
''irchnw:  Descendenz  u.  Pathologie.     Virch.  Arch.,  lO;}  Bd.,  1886. 
^Vag-ner:  Die  Kranklieitsaulage.  '  Deutsch.  Arcii.  f.  kiiu.  Med.,  23  Bd.,  1888. 
Viedersheim :  Der  Bau  des  Meuscheu,  Freiburg,  1902. 
•      Sec  also  J=  17. 

§  16.     The   origin     of    congenital    pattiological    aniage    -that    is, 

f  diseases  in  Mhich  extrinsic  influences  are  either  entirely  ab.sent  during: 
oth  intra-  and  extra-uterine  life,  or  are  of  significance  only  as  a  source 
f  irritation  sufiBcient  to  excite  into  development  pathological  teudencies 
Iready  present  in  the  body — may  be  explained  in  two  ways :  Either  the 
(itholofiical  ^peculiarities  of  the  individual  concerned  are  inherited  from  the 
iirc.stors,  or  they  are  developed  from  the  seed,  i.e.,  from  the  individual  sexual 
iirh'i  that  have  coxndated  or  from  the  segmentation  nucleus  resulting  from 
irir  union. 

The  inheritance  of  pathological  qualities  is  a  fact  clearly  shown  by 
liiiical  observations,  inasmuch  as  many  of  the  examples  of  diseases  due 
)  intrinsic  causes  which  are  cited  in  §  15  also  appear  as  inheritable 
I  lai  act  eristics  in  certain  families.  In  some  cases  these  characteristics 
re  transmitted  from  the  parents  to  the  children,  in  other  cases  the 
laii.lchild  may  exhibit  pathological  peculiarities  of  the  grandparents, 
If  ])arents  themselves  remaining  exempt;  finally,  in  other  cases  the 
atliological  peculiarity  may  be  manifested  in  individuals  of  tlu^  collat- 
tal  l)ranclies,  as  from  uncle  to  nephew.  Dwarfishness  and  giantism  are 
atliological  peculiarities  which  frequently  characterize  cei'tain  families. 
i\  lingers,  cleft-hand  aud  cleft-foot,  hare-lip,  dextrocardia,  birth-marks, 
inlliple  exostoses,  fibromato.sis  of  the  nerves,  aud  multiple  neurofibro- 
lata  may  appear  in  families  for  many  successive  generations. 

('t)ngenital  haemophilia  is  also  an  inheritable  condition,  which  is 
idinarily  transmitted  through  the  daughter  to  a  male  grandchild,  the 
aughter  not  showing  the  disease.  There  may  occur,  however,  a  direct 
ansinission  of  haemophilia  from  parents  to  childicn.  Partial  or  total 
)l()r -blindness  also  occurs  as  an  inh('rital)le  family  di.M'a.se.  esj)ccially 
nfecting  the  male  members,  and  like  ha-mopliilia  is  iiansniilted  tlirough 
le  female  line,  which  does  not  suffer,  to  th(^  male  descendants.  The 
•pical  pigment-degeneration  of  the  retina,  myopia,  deaf-mutism,  cer- 
lin  forms  of  progressive  muscular  atrophy,  and  polyuria  (Weyl)  are 
•so  inheritable. 

According  to  Gairdner  and  Garrod,  in  about  ninety  per  cent  of  the 
i.^cs  of  gout  there  is  a  family  history  of  the  disease. 

Of  the  pathological  conditions  of  the  nervous  system  many  are  in- 
■I  if  aide;  to  these  belong  especially  periodic  and  circular  insanity, 
)ilt  psy,  hysteria,  congenital  insanity,  and  to  a  somewhat  less  extent 


54  THE    IXTRIXSIC    CAUSES    OF    DISEASE. 

melancholia,  mania,  delusional  insanity,  and  alcoholism.  Progressiva: 
paralysis,  the  deliriums,  and  the  conditions  of  nervous  exhaustion  an 
but  slightly  inliueneed  by  heredity  (Kraepelin).  Hagen  estimates  ihi 
number  of  hercdilaiy  insane  at  28.9  per  cent,  Leidesdorf  at  25  per  ceuti 
Tigges  at  o\er  4(1  per  cent  of  all  cases,  while  Forel  holds  that  G9-85  pe> 
cent  have  liereditary  taint. 

In  the  most  severe  forms  of  hereditary  degeneration  the  pathologica 
condition  itself  is  inherited,  but  more  frequently  the  predisposition  t( 
disease  is  alone  inherited  and  the  morbid  condition  itself  is  develope( 
through  the  action  of  extrinsic  harmful  influences  upon  the  central  uer 
vous  system.  The  character  of  the  disease  in  the  descendants  may  bi 
the  same  as  in  the  ancestors  {idnitical  heredity).  More  often  the  charac 
ter  of  the  disease  is  changed  (transfonndtional  heredity),  not  infrequentb 
in  the  sense  that  the  severity  of  the  condition  increases  from  generatio] 
to  generation  {degenerative  heredity). 

According  to  Morel,  there  may  appear,  for  example,  in  the  first  geu 
eration,  nervous  temperament,  moral  depravity,  excesses ;  in  the  second, 
tendency  to  apoplexy,  severe  neuroses,  alcoholism ;  in  the  third,  psychi 
cal  disturbances,  suicidal  tendency,  intellectual  incaj)acity;  finally,  ii 
the  fourth,  congenital  idiocy,  malformations,  and  arrests  of  development 

The  occurrence  of  inheritable  diseases  is  by  no  means  remarkable 
it  is  a  well-known  fact  that  in  a  family  not  only  the  peculiarities  of  race 
but  also  of  that  particular  family  are  inherited,  and  that  very  often  tli 
characteristic  qualities  of  either  parent  or  of  both  recur  in  the  children 
As  a  hypothesis  for  the  explanation  of  heredity,  it  is  only  necessary  t' 
assume  that  the  peculiar  quality  under  consideration  represents  no 
merely  a  somatic  change  accidentally  acquired  during  the  life  of  the  an 
cestor,  but  much  rather  a  quality  of  the  ancestor  developed  from  a  con 
genital  anlage.  Diseases  which  in  a  normal  individual  arise  only  uii 
der  the  influences  of  some  external  injurious  influence  are  never  in  atru 
sense  inherited  (compare  §  17),  but  only  those  pathological  condition 
existing  in  the  germ  are  to  be  regarded  as  examples  of  true  inheritance 
If  a  certain  disease,  as,  for  example,  a  mental  disease  or  myopia,  is  tb 
product  of  a  special  inherited  predisposition  plus  the  effect  of  injuriou 
influences  which  have  acted  upon  the  body  during  life,  only  that  par 
can  be  transmitted  which  has  its  seat  in  some  peculiar  congenital  anlage 
but  not  that  caused  by  external  influences — the  acquired  condition  can 
not  be  inheiited. 

In  direct  inheritance — i.e.,  in  that  form  of  inheritance  in  whic] 
parental  qualities  are  transmitted  to  the  child — the  transmission  of  nor 
mal  as  well  as  of  pathological  qualities  is  possible  only  when  both  sexun 
cells,  in  the  condition  in  which  they  combine,  contain  the  potentialitie 
of  the  characteristics  of  both  parents,  in  so  far  as  these  characteristic 
are  tiansmissilfle.  The  product  of  the  union  of  the  sexual  cells — th 
segmentation-cell— must,  therefore,  contain  within  itself  both  the  pa 
ternal  and  maternal  (|ualities.  Since  the  sexual  cells  do  not  represen 
a  product  of  tin'  body  develoi)ing  during  the  course  of  life,  but  are  rathe 
to  be  regarded  as  inde])(Mident  structui-es,  which  at  an  early  period  o 
development  are  separated  from  the  other  parts  of  the  body  (that  is,  froi; 
the  somatic  cells)  into  special  organs,  Avhere,  protected  and  nourished  b; 
the  body  to  whidi  they  belong,  they  lead  an  independent  existence;  th 
only  i)ossible  explanation  for  the  phenomenon  of  inheritance  is  found  i 
the  hypotliesis  that  the  individual  sexual  cells  contain,  from  the  time  o 
their  origin  onward,  the  potentialities  of  the  same  qualities  which  appea 


THE    IXIIKKITAXCE    OF    DISEASE.  "> 

ill  the  body  in  which  tlioy  dwoll.  IJoth  the  sexual  eells  and  the  body 
itself,  therefore,  iiduMJt  ii!  general  the  same  (pialities  from  the  aneestoi-s. 
Since  in  tlie  M't  of  fructification  only  the  nucU'i  of  the  scxuiil  cells — that 
i>,  parts  of  the  sauu' — Ci)uie  to  copuhition,  we  are  compeUed  further  to 
assuiiie  that  the  nuclei  are  the  bearers  of  inheritabh'  (|nalilies,  and  tlie 
peculiarities  of  the  individual  aiisin-;- iiom  the  comhinaliou  of  the  sex- 
ual nuclei  have  their  fouiuhition  in  the  or<;anization  of  tlie  nuclei. 

The  appearance  in  the  descendants  of  nonnal  or  i)atholo<;ical  char- 
acters belonging  to  the  collateral  relatives  (uncle,  great -aunt,  or  cousin), 
j  but  which  are  not  present  in  the  parents,  is  known  as  collatrral  iit/irri- 
\  tanee.     This  phenomenon  is  explained  by  the  hypothesis  tluit  the  sexual 
I  cells,  in  their  origin,  received  characteristics  Avhich  the  bodies  of  the 
I  parents  did  not  receive,  oi-  which,  at  least,  did  not  undeigo  development 
and  manifest  themselves  in  the  ixu'ental  boilies,  whereas  in  certain  rela- 
tives they  did  become  manifest. 

The  appearance  in  an  individual  of  normal  or  pathological  character- 
istics which  were  wanting  in  the  i)arents,  but  were  present  in  the  grand- 
parents or  great-grandparents,  is  known  as  atavistic  inheritance.  This 
phenomenon  is  explained  by  the  hypothesis  that  given  characteristics  of 
the  grandparents  or  great-grandparents  were  tiansmitted  to  the  sexual 
cells  of  the  son,  or  of  the  son  and  grandson,  without  developing  in  the 
body  of  the  first,  while  the  quality  thus  remaining  latent  became  again 
manifest  in  the  grandson  or  great-grandson. 

The  attempt  has  been  made  to  give  to  the  atavistic  mode  of  transmis- 
sion— which  is  of  frequent  occurrence  and  is  usually  confined  to  the 
immediate  generations  of  ancestors — a  wider  significance  in  pathology. 
Thus  it  has  been  proposed  to  explain  the  occurrence  of  numy  iiewlj-  aris- 
ing pathological  conditions,  which  appear  similar  to  certain  somatic 
qualities  possessed  by  remote  animal  species  in  the  ancestry  of  man,  as  a 
reversion  to  the  type  of  these  ancestors.  For  example,  microcei)halus 
and  micrencephalus  have  been  explained  as  a  reversion  to  the  ape  type ; 
and  Lombroso  is  inclined  to  regard  the  homo  delinquens  as  an  atavistic 
phenomenon.  There  can  be  no  doubt  that  certain  writers  have  gone  too 
far  in  this  respect  and  have  mistaken  certain  acquired  pathological  for- 
mations or  new  germ-variations  (compare  §  17)  for  atavistic  conditions. 
Aside  from  the  question  of  reversion  to  the  type  of  the  nearest  genera- 
tions of  ancestors,  atavism  plays  but  an  insignificant  part  in  pathology, 
and  it  can  really  be  emi)loyed  only  in  the  explanation  of  pathological 
formations  in  which  the  tissues  show  a  certain  fluctuation  of  beha\  ior, 
so  that  not  rarely  formations  arise  which  in  phytogeny  or  ontogeny  rep- 
resent stages  of  the  then  normal  conditions.  In  this  category  belong,  for 
example,  the  occurrence  of  certain  forms  of  the  ear,  supernumerary  ribs, 
nipples,  or  mammary  glands,  and  the  development  of  certain  muscles 
which  are  found  in  the  most  closely  related  mammals. 

It  is  held  by  many  writers  tluit  in  in/Iiriifunl  ni.s,s,  urt/i/irctl  />,it/i»for;ic(il  coiuJitiona 
may,  under  cerUiiii  rirruiiisdtiirrs,  he  traiisinitleil  ^^  t/ir  (/,. •«•,■„</, nifs.  Some  even  aflinn 
the  possibility  of  liereditary  traiisiiiissioii  of  tlet'ormilies  caused  by  injury,  and  re^^ard 
such  transmission  as  proved  in  certain  cases,  hi  support  of  their  view  they  tjclieve 
that  they  can  refer  to  the  hereditary  transmission  of  birth-marks,  malformations  of  tlie 
fingers,  myopia,  mental  diseases,  predisposition  to  tul)erculosis,  etc.,  as  examples,  ac- 
cording to  their  assumption,  of  diseases  which  appeared  in  the  first  instance  as  ac- 
quired, and  which  were  then  transmitted  tf)  the  descendants.  Furtlier,  they  hold  that 
they  can  point  to  observations  on  animals,  of  which  numerous  accounts  are  found  in 
the"^  literature,  as  giving  evidence  that  injuries  may  cause  deformities  which  are  later 
transmitted  to  tlie  offspring. 


56  THE    INTRINSIC    CAUSES    OF   DISEASE. 

An  unprejiulifod  oxamination.  however,  of  the  material  collected  in  support  o: 
this  view  shows  that  nh.s,  rr,itini,.s  irliirh  (.stithlish  the  hereditary  transmission  of  patJiolog 
ical  characti  ri.sfir.s  ifijnlr,  ,1  i,,  tlw  iiuUciihinl  do  not  exist.  The  alleged  proofs  are  founc 
iu  part  to  be  based  upon  iiiaicunite  observations,  in  part  upon  incorrect  inferences 
drawn  from  accurate  observations.  For  example,  the  assumption  that  the  occurrenct 
of  a  birth-mark  in  a  child  in  the  same  region  of  the  skin  as  tliat  in  wliich  the  mothei 
has  a  scar  is  a  proof  of  iuheriteil  deformity  is  wholl}'  in  the  wrong,  inasmuch  as  birth 
marks  and  scars  represent  two  entirely  dillerent  pathological  processes.  If,  among  tht 
descendants  of  a  man  who  suffered  from  some  form  of  mental  disease  and  who  showed 
this  disease  only  after  a  certain  age  through  the  perversity  of  his  actions,  there  appears 
an  inheritable  disease  of  the  central  nervous  system,  or  if  we  note  a  similar  occurrence 
in  the  case  of  myopia,  we  cannot  conclude  from  such  observations  that  the  disease  ol 
the  ancestor  was  purely  an  acquired  condition.  The  term  acquired,  in  the  biological 
sense,  can  be  applied  only  to  that  which  in  the  course  of  the  life  of  an  individual  arises 
purely  from  extrinsic  influences,  but  not  to  a  cjuality,  the  anlage  of  wliich  existed  al- 
ready* in  the  germ-cell,  although  this  quality  did  not  become  manifest  until  excited  tc 
development  by  extrinsic  influences.  Should  there  appear  in  a  family  inheritable  men- 
tal diseases  or  hereditary  myopia,  the  first  case  of  such  diseases  may  have  already  been 
due  to  some  pathological  alteration  of  the  germ,  although  no  manifestations  of  the  dis- 
ease occurred  until  some  of  the  outside  influences  of  life  excited  it  to  activity,  and  so 
rendered  pos.sible  the  recognition  of  the  pathological  condition.  The  particular  patho- 
logical condition  in  this  case  cannot,  therefore,  be  regarded  as  a  purely  acquired  disease. 

The  observations  of  Brown-Sequard  that  guinea-pigs,  in  which  epilepsy  has  been 
experimentally  induced,  can  transmit  the  condition  of  epilepsy,  have  been  shown  by 
Sommer  to  be  incorrect,  in  that  the  condition  is  not  a  true  epilepsy,  but  a  reflex 
epileps}',  and  is  not  transmitted. 

Against  the  occurrence  of  an  inheritance  of  acquired  pathological  conditions  is  the 
simple  consideration  that  the  human  race,  which  is  exposed  to  so  many  injurious  influ- 
ences, and  whose  individual  members  suffer  so  frequently  from  disease  and  mutilations, 
would  very  soon  arrive  at  a  state  of  extreme  misery  and  stunted  growth  and  would 
eventually  perish  were  only  a  small  part  of  the  acquired  diseases  transmitted  to  the 
descendants.  Further,  the  origin  of  man  and  animal  forms  reproducing  through  ger- 
minal cells  is  in  itself  an  argument  against  the  possibility  of  the  transmission  of  qualities 
acquired  by  the  individual. 

The  act  of  fructification — that  is,  the  first  step  leading  to  the  production  of  a  new 
individual — is  accomplished  by  the  copulation  of  the  sexual  nuclei — that  is,  of  the 
nuclei  of  the  ovum  and  spermatozoon.  According  to  the  researches  of  the  last  decades, 
there  can  be  no  doubt  that  tliese  nuclei  are  the  bearers  of  the  hereditary  characteristics  of 
the  parents,  and  that  the  individuality  of  the  copulating  nuclei  is  inherent  in  the  or- 
ganization of  the  same.  It  is  impossible  to  conceive  in  what  manner  processes  taking 
place  in  the  body  cells  can  produce  in  the  sexual  nuclei,  which  lie  within  special  ceils 
in  the  sexual  glands,  such  alterations  of  organization  that  they  shall  contain  in  poten- 
tial form  the  acquired  characteristics  of  the  body  and  transmit  them,  after  copulation 
has  occurred,  to  the  descendants. 

Delage  was  able  to  fructify  non-nucleated  portions  of  the  eggs  of  echiuoderms, 
annelides,  and  raollusks  with  spermatozoa  (merogony).  He  regards  the  union  of  the 
nucleus  of  the  spermatozoon  with  tlie  protoplasm  of  the  egg  as  the  essential  feature  of 
fructification.  This  is  not  applicable  to  the  ordinary  method  of  fructification,  but  only 
shows  that  in  exceptional  cases  the  entrance  of  the  spermatozoon  into  the  protoplasm 
of  the  t'gg  is  suflicient  for  the  setting-up  of  further  development,  and  that  the  nucleus 
of  the  spermatozoon  entering  into  the  egg  without  uniting  with  the  nucleus  of  the  lat- 
ter exercises  an  especial  influence  upon  the  protoplasm  of  the  egg. 

Daririn  in  his  time  represented  the  view  that  acquired  cJiaracteristics  could  be 
transmitted  to  the  descendants,  and  endeavored  to  make  such  phenomena  intelligible 
by  the  theory  that  molecules  from  all  the  cells  of  the  body  contribute  to  the  formation 
of  the  germ-cells,  and  that,  consequently,  alterations  of  the  organism  can  be  trans- 
mitted tothe  germ-cell.  Nevertheless,  there  occur  in  the  writings  of  Z>a7m/i  state- 
ments which  not  only  do  not  agree  with  this  opinion,  but  directly  contradict  it. 

At  the  present  time  the  views  with  regard  to  the  inheritance  of  disease  generally 
accepted  are  that  there  is  no  true  inheritance  of  infections  and  that  gross  structural  dis- 
turbances cannot  be  inherited.  Tlie  only  possible  inheritance  of  conditions  acquired 
by  the  parents  is  that  of  conditions  acting  both  upon  the  somatic  tissues  and  germ-cells 
of  the  parents.  Chemical  and  physical  conditions  acting  within  the  body  or  from  with- 
out may  cause  changes  in  the  constitution  of  somatic  and  germ-celis.  the  occurrence 
of  sucli  changes  in  the  germ-cells  is  clearly  shown  in  the  effects  upon  the  progeny  of 
paternal  or  maternal  alcoholism,  plumbism,  and  experimentally  with  abrin.     It  is  a 


ixiif:kitaxce  of  pathological  coNnriioxs.  57 

■well-known  fact  that  in  the  case  of  the  birth  of  monsters  there  is  often  oljtiiinable  a 
history  of  some  infection  in  one  of  the  iiareiits  before  conception  took  i)lace.  Hardeen's 
experiments  regarding  tlie  ciiuuges  in  embryos  arising  from  ova  fertilized  by  sper- 
matozoa that  had  been  injured  by  Roentgen  irradiation  are  very  suggestive. 

vl<?(jwi  has  applied  the  side-chain  theory  in  explanation  of  heredity.  According 
to  this  view  there  may  be  also  a  true  inheritance  of  morbid  conditions  due  to  modifica- 
tions in  tlie  biophoric  molecules  through  tlie  interaction  of  their  side-chains. 

Recently  much  discussion  has  been  waged  over  the  principles  of  lieredity  involved 
iaJJeiH/cl's  late,  Galtoii's  hue,  and  De  Vries'  ihionjof  mutatiouH  (see  literature). 

Literature. 

{Inheritance  of  Pidliolof/icdl   (^inditionfi.) 

Adami:  Hereditv  in  Relation  to  the  Development  of  Morbid  States.  Kef.  Hand- 
book of  Med."Sc..  1902;   Osier's  Modern  Medicine,  1907. 

Bateson:  Mendel's  Principles  of  Heredity ,  London,  1902. 

Bernhard:  Familiare  Erkrankung  d.  Centralnervensystems.  Virch.  Arch.,  126  Bd., 
ISill. 

Bollinger:  Ueber  Vererbung  von  Krankheiten,  Stuttgart,  1882. 

Brown-Sequard:   Arch,  de  phys.,  i.,  1868,  ii.,  1869,  iii.,  1870,  iv.,  1872  (giebt  an,  dass 

kimstlich    erzeugte   Epilepsia  bei   Meerschweinchen   auf  die   Jungen    iibergehen 

konne). 
Couvelaire:   La  dysostose  cleido-cranienne.     J.  de  phys.,  i.,  1899. 
Darwin,   C.   H. :    Die  Ehe  zwischen  Geschwisterkindern   und  ihre  Folgcn,  Leipzig, 

lS7(i. 
Dejerine:   L'heredite  dans  les  maladies  du  systeme  nerveux,  Paris,  1886. 
Delage:   Etude  sur  la  merogonie.     Arch,  de  zool.  exper.,  1899. 
Deutschmann:    ^■ererbung  v.    erworb.   AugenafTectionen.     Zehnder's  kl.  Monatsbl., 

xyiii.,   1880. 
Dietrich:   Die  Bedeutung  der  Vererbung  fiir  die  Pathologic,  Tubingen,   1902. 
Fischer:    I'eber   hereditare   multiple   Exostosenbildung.     Dtsch.    Zeitschr.   f.   Chir., 

xii.,  1880. 
Galton:  Natural  Inheritance,  London,  1889;  Proc.  Roy.  Soc,  1897. 
Grandidier:   Die  Hiimophilie,  ii  Aufl.,  1877. 

Griesinger:   Die  Pathol,  u.  Ther.  der  psych.  Krankheiten,  7  Aufl.,   1892. 
Gutzmann:    Vererbung  v.  Sprachstorungen.     Deut.  med.  Woch.,  1898. 
Hagen:    Statist.  Enters,  liber  Gei.steskrankheiten,  1876.     Ueber  die   Verwandtschaft 

des  Genies  mit  dem  Irresein.     Allg.  Zeitschr.  f.  Psych.,  xxxiii. 
Henle:   Handbuch  der  rationellen  Pathologic,  i.,  Braun.schweig,  184(). 
Herrmann:    Die  Vererbung  v.  path.  Zustanden  beim  Pferde.     A'ortr.  f.  Thieriirzte, 

viii.,  1,  1885. 
Hossli:  Geschichte  und  Stammbaum  der  Bluter  von  Tenna,  Inaug.-Di.ss.,  Basel,  1885. 
Israel:  Angeb.  Spalten  der  Ohrlappchen.     Virch.  Arch.,  119  Bd.,  1890. 
Mayer:   Spalthand  u.  Spaltfuss  (durch  4  Generat.  vererbt.).     Beitr.  v.  Ziegler,  xxiii., 

1898. 
Morel:    De  l'heredite  morbide  progressive,  Paris,  1867. 

V.  Nathusius:    Die  Vorgiinge  der  Vererbung  bei  den  Hausthieren,  Berlin,  1891. 
Pearson:    Law  of  Ancestral  Heredity.      Proc.  Roy.  Soc,  1898;  Law  of  Reversion. 

Ibid.,  1900. 
Reinecke:    Erblichkeit  der  multiplen  Wachsthum.sexosto.sen.     Beitr.  v.  Bruns,  viii., 

1891. 
Roth:    Die  Thatsache  der  Vererbung,  Berlin,  1885.     Der  gegenwiirtige  Stand  der 

Frage  der  Vererbung  erworbener  Eigenschaften.     Wiener  Klinik,  7   IL,  Wien, 

1890.^ 
Saury:  Etude  clin.  sur  la  folie  hdreditaire.  Paris,  1886. 
Sioli:   Vererbung  von  Gei.ste.skrankheiten.     Arch.  f.  P.sych.,  xvi.,  18S5. 
Sommer:      Die    Brown-S6quard'sche     Meer-schweinchenepilepsie.     Beitr.   v.    Ziegler, 

xxvii.,  1900. 
Thoma:   Ueber  einige  senile  Veriinderungen  des  Korpers,  Leipzig,  1884. 
Virchow:    (lesammelte  Abhandlurigen,  Fnmkfurt,  1856;  Virch.  Arch.,  103  Bd.,  1886. 
De  Vries:    Die  Mutationstheorie,  .Jena,  1901. 

Weil:    Die  horerlitare  Form  des  Diabetes  insii)idus.     Virch.  Arch.,  95  Bd.,  1884. 
Zander:    1st  die  Polydaktylie  theromorphe  Varietiit  oder  .Missbildung?     Virch.  Arch., 

125  Bd.,  1891. 


58  THE    INTRINSIC    CAISES    OF    DISEASE. 

Zieg-ler:   Konnen   erworbene   patholosische   Eigenschaften    vererbt   werden   u.    w 
entstehen  erbliche  Krankheiten  u.  Nlissbildunfien?     Beitr.  v.  Ziegler,  i.,  1886;   D 
neuesten  Arbeiten  fiber  Vererbungs-  u.  Abstammungslehre  u.  ihre  Bedeutung 
d.  Pathologic,  ib.,  iv.,  18S8. 
See  also  §  15  and  §  17. 

§  17.  As  has  been  explaiued  in  §  17,  inherited  diseases  ore  cdicays  such  c 
have  at  the  very  frst  deveJoped  from  intrinsic  causes,  that  is,  from  certai 
anlage  in  the  germ-cells  ;  or  at  least  are  diseases  in  tchich  the  predispositio 
thereto  is  a  congenital  characteristic.  Conversely,  the  statement  m^y  b 
niade///o/  all  normal  or  pathological  qualities  in  the  germ-cells  are  inheritabh 

Tlie  first  appearance  of  new  pathological  characteristics  which  ar 
inheritable  may  be  dependent  npon  the  fact  that  as  a  resnlt  of  sexua 
procreation — i.e.,  of  the  nnion  of  two  sexnal  nnclei,  one  of  which  is  th 
bearer  of  the  transmissible  qualities  of  the  father,  the  other  of  those  c 
the  mother — new  variations  are  coustautly  arising,  so  that  the  child  i 
never  exactly  like  one  parent ;  but,  on  the  other  hand,  in  addition  to  th 
qualities  which  the  parents  offer,  it  possesses  also  new  qualities.  Eve 
if  we  assume  that  the  sexual  nuclei  at  times  contain  in  potential  fori 
exactly  the  same  characteristics  as  those  of  the  parents,  the  product  it 
suiting  from  the  copulation  of  these  nuclei  would  jjresent  a  certai 
degree  of  variation.  In  such  a  case,  howe^'er,  the  differences  betwee 
the  children  of  such  parents  would  be  but  slight.  As  a  matter  of  taci 
the  different  products  of  the  same  parents  may  show  an  infinite  variet} 
by  reason  of  the  fact  that  the  germ-cells  themselves  contain  further 
mixture  of  the  transmissible  characteristics  of  the  paternal  and  matern; 
ancestors,  and  that  this  mixture  is  never  the  same  in  the  individui 
germ-cells. 

In  accordance  with  this  is  the  fact  that  the  children  of  a  certain  fan 
ily  always  j) resent  important  differences  in  both  physical  and  ment; 
qualities.  A  marked  resemblance  occurs  only  in  the  case  of  twins  ari> 
ing  from  one  egg — i.e.,  when  the  process  of  development  of  both  chi] 
dren  has  started  from  the  same  act  of  copulation. 

The  embryonal  variations  resulting  from  the  mixture  of  two  indi 
vidually  different  hereditary  tendencies  can  find  their  expression  i 
the  most  varied  qualities  of  the  body  and  mind  of  the  developing  chik] 
If  these  do  not  deviate  in  a  marked  degree  from  the  characteristics  wliic 
the  different  members  of  the  family  show,  the  conditions  are  regarded  a 
normal  and  ordinarily  receive  no  especial  attention.  If,  on  the  con 
trary,  important  differences  of  character  are  produced,  the  occurrenc 
attracts  greater  attention;  and,  according  to  the  value  which  it  has  fo 
the  imli\idual  concerned,  is  regarded  at  one  time  as  something  favoi 
able,  at  another  time  as  something  unfavorable,  something  pathological 
AVTien  small,  weak  parents  produce  children  who  develop  into  large  am 
strong  individuals,  or  when  the  intellectual  capacity  of  the  children  sui 
passes  that  of  the  parents,  the  occurrence  is  regarded  as  favorable.  It 
as  actually  happens,  a  genius  in  any  branch  of  human  knowledge  or  skil 
suddenly  appears  within  a  family,  without  any  evidence  of  an  especiall; 
marked  mental  development  in  the  ancestors,  the  phenomenon  Mouh 
attract  general  attention  and  be  regarded  as  a  fortunate  event.  But  if 
on  the  other  hand,  strong  parents  beget  children  who  are  weak  o 
physically  defective,  or  if  they  show  a  mental  development  inferior  t. 
that  of  their  parents,  or  if  they  show  a  complete  stunting  of  a  part  o 
their  mental  faculties,  the  ncxchj  appearing  variation  is  regarded  as  abnor 
mat,  pathological. 


THEORIES    OF    TMIEIUTAXCE.  59 

If  we  consider  the  experiences  which  the  ])iilh(»h)<;y  (tf  iiiaii  and  ani- 
mals furnishes,  the  assumption  seems  fully  warranh'd  tliat  of  llu; 
transmissible  pathological  conditions  and  predispositions,  \<  ly  many, 
pcihaps  the  maJDrily,  are  referable  to  a  variation  of  the  germ  based 
upon  the  amphimixis.  For  oxamplc,  tlic  iiioup  of  hereditary  patlio- 
louical  conditions  and  i)redispi)sitions  of  the  central  nei'vons  system, 
hereditary  myopia,  luemophilia,  i>ij;inentation  of  the  retina,  and  poly- 
^dactylism  may  arise  in  this  manner.  If  such  ahnormal  characteristics 
•  show  themselves  repeatedly  in  the  childien  of  the  parents,  who  are  them- 
I selves  normal  and  have  healthy  ancestoi-s,  it  may  be  assumed  tliat  the 
^germ-cells  of  the  parents,  though  individually  normal,  have  through 
jtheir  union  given  rise  to  a  pathological  vai-iation.  This  liypothesis  be- 
, comes  substantiated  when  one  or  both  parents  produce  normal  olfspring 
; through  copulation  with  other  individuals. 

Besides  the  variations  which  are  the  result  of  normal  sexual  repro- 
,  duction,  it  is  very  probable  that  i)athological  germ-variations  which  lead 
I  to  the  development  of  transmissible  i)athologieal  ((ualities  may  also  arise 
through  the  action  of  injurious  influences  upon  the  sexual  nuclei  or  the 
)  segmentation  nucleus  ;  or  else  that  the  process  of  copulation — that  is, 
jtlie  union  of  the  sexual  nuclei — has  been  disturbed  in  some  manner. 
\  The  injurious  substance  may  be  a  body-product,  or  it  may  come  from 
I  without,  and  at  the  same  time  also  produce  its  harmful  effects  upon  the 
.body.     Consequently,  in  these  cases  we  may  speak  of  the  germinal  ac- 
quisition o/  a  transmissible 2>((thoIo(/ical  clKirdcicri.stic  iliroiif/li  the  <(ctioii  of 
]  an  extrinsic  injurious  injiuenee.    This  does  not  mean,  however,  as  has  been 
accepted  bj"  many,  that  the  tissues  of  the  body,  under  the  inlluence  of 
extrinsic  harmful  iutlueuces,  first  suffer  changes  in  themselves,  and  then 
.  transfer  these  changes  to  the  germ-cells.     It  is  to  be  believed,  rather, 
i  that  the  harmful  influence  acts  directly  upon  the  sexual  nuclei  or  the 
,  segmentation-nucleus,  producing  in  these  a  change  of  some  lind,  which 
i  later  leads  to  a  pathological  development  of  the  individual  developing 
.  from  the  impregnated  egg.     It  is  a  matter  of  no  importance,  so  far  as 
the  natuie  of  the  resulting  pathological  variation  is  concerned,  whether 
the  somatic  tissues  also  suffer  changes,  or  of  what  nature  such  changes 
may  be. 

If  a  transmissible  pathological  characteristic  arises,  it  may,  in  case  it 
does  not  affect  life  or  prevent  reproduction,  actually  be  transmitted,  al- 
though this  does  not  necessarily  follow.  The  chances  that  a  particular 
characteristic  will  be  transmitted  are  greatest  when  both  i)ai'ents  ])ossess 
the  same  quality,  as,  for  example,  when  both  ])aients  ai«'  affected  with 
hereditary  deaf-mutism  or  with  near-sightedness.  Jf  the  characteristic 
is  wanting  in  one  parent,  there  is  pioduced  most  fre(|uently  a  new  g<'rm- 
variation,  in  Mhich  the  pathological  characteristic  fails  entirely  to  mani- 
fest itself,  and  in  the  following  generations  may  completely  disiipjjcar. 
If  several  descendants  are  begotten,  the  pathological  chaiacteristic,  in 
case  it  is  not  wholly  lost,  may  show  itself  in  oidy  a  few  of  the  desctMid- 
ants,  and  in  these  in  either  a  modified  or  in  an  aggravated  form.  Not 
rarely  it  happens  that  the  characteristic  remains  latent  in  one  generation 
—that  is,  is  confined  to  the  sexual  cells,  and  appears  again  in  the  second 
generation. 

There  seems  to  me  to  bo  no  dmilit  that,  through  the  copiilatinii  of  two  scxnul 

\  nuclei  possessing  difTeieul  hereditary  tendencies,  variations  may  he  produced,  and  that 

among  these  there  may  be  some  wliich  are  to  be  regarded  as  pathological.     It  is  mf)re 

difticult  to  answer  the  question  whether,  besides  these,  there  are  not  also  transmissit)le 

variations  of  a  pathological  nature,  whidi  arise  through  intiuences  whicli  atlect  tlie 


60  THE    IXTRIXSIC    CAITSES    OF    DISEASE. 

nuclei  of  the  ova  or  of  the  spermatoiionia.  ihc  spermatocytes  or  spermatosonies,  or  th( 
segmeutation-uuclcus;  and  further,  if  wr  accei't  the  existence  of  such  variations,  witt 
what  frequency  do  they  occur.  Wiisi/i.nm  holds  the  opinion  that  the  basis  of  transmis 
sible  variations  is  to  be  found,  not  in  the  amphimixis,  but  rather  in  the  direct  action  of  ej 
ternal  inlluences  upon  the  .sexual  nuclei.  Starting  from  the  assumption  that  the  variabl 
cells  or  cell-groups  derived  from  the  germ  (by  him  designated  as  Jiereditnry  jneces  o 
determinates)  are  represented  in  the  germ-plasma  by  special  particles,  which  are  forme" 
by  the  grouping  together  of  a  number  of  Ufe-tr<>ph„hh(sis  or  bfopJiores  (molecular  group 
which  represent  the  smallest  units  of  life),  and  which  he  calls  determinants  or  determn 
ing  pieces,  he  believes  that  he  is  warranted  in  ascribing  the  transmissible  variatio 
primarily  to  the  changes  produced  by  external  influences  in  the  determinants  or  grou 
of  determinants  contained  within  the  nuclear  chromatin,  so  that  finally  the  hereditai 
pieces  or  determinates  derived  from  them  also  sufler  changes.  He  believes  that  sue 
an  influence  might  be  exerted  by  excessive  nourishment  of  a  determinant,  causing  it  1 
jrrow  more  raiiidly.  For  example,  he  regards  it  as  possible  that  many  congenital  raai 
formations  (for  example,  an  increase  in  the  number  of  fingers  and  toes)  can  be  referre 
to  a  reduplication  of  the  determinant-groups  caused  by  increased  supply  of  nourisli 
mcnt.  According  to  Weismnnn,  the  amphimixis  has  only  a  secondary  influence  in  th 
origin  of  a  permanent  variation,  in  that  it  mixes  in  constantly  new  manner  the  varij 
tions  dependent  upon  the  changes  in  the  determinants,  but  does  not  in  itself  produ( 
new  variations.  "The  deviations  which  the  determinants  suffer  through  unequal  co] 
ditious  of  nutrition  constitute  the  material  out  of  which,  through  amphimixis  in  co] 
nectiou  with  selection,  the  visible  individual  variations  are  produced,  through  who 
increase  and  combination  new  forms  arise." 

I  agree  with  Weismann  in  so  far  as  the  assumption  that  the  appearance  of  a  ne 
variation  of  pathological  nature  is  in  part  to  be  referred  to  changes  in  the  determinani 
contained  within  the  sexual  nuclei,  due  to  the  direct  action  of  extrinsic  influences, 
do  not,  however,  believe  that  there  is  sufficient  ground  for  attributing,  as  does  Wei 
manji,  the  formation  of  new  separate  parts  to  an  over-nourishment  of  single  groups  ( 
determinants.     Such  a  dependence  of  the  germ-plasma  upon  the  surrounding  nutritii 
material  seems  to  me  scarcely  conceivable,  and  is  opposed  to  all  views  hitherto  held  r 
garding  the  nutrition  of   cells.     Not  oidy  quantitative  but  much  rather  qualitatii 
changes  of  the  food-material  would  appear  to  be  necessary  in  order  to  produce  change 
in  the  organization  of  the  determinants.     Further,  I  hold  that  the  amphimixis  has  ni 
only  a  secondary  but  much  more  a  primary  significance  with  regard  to  the  origin 
pathological  variations,  in  the  sense  tliat  it  itself  is  able  to  produce  new  variatior 
Finally,  it  seems  to  me  that  we  cannot  at  the  present  wholly  set  aside  the  hypothes 
of  A'd;/(h\  according  to  Avhich  the  idioplasm  is  capable  of  altering  its  own  condition 
from  witliin  outwaid,  in  certain  fixed  directions  and  according  to  certain  fixed  laws 
and  thus  may  produce  new  characteristics. 


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Thierined.,  18  Bd.,  1891;   Vererbung  erworbener  Eigenschaf ten.     Biol.  Centralbl., 
;         xiii.,  1893. 
j         See  also  §§  15  and  16. 

'  §  18.  Beside.s  tlieiiilieritable  patlioloo-ieal  roiKlitioiisnifiilioiMMJ  ahoNc, 
lluMc  aj^peurs  to  be  a  hereditary  transmission  in  the  case  of  the  infec- 
tious diseases;  but  this  i.siii  reality  not  a  true  form  of  inheritance,  and 
lis  moie  ])ioi)eily  designated  a.s  postconceptional  intra=uterine  infection. 
;  If  patlio^t;eiiic  micro-orgaiiisins  enter  into  the  Itlood-sticani  oi'  a  pr«'g- 
inant  woman  they  may  be  earned  into  tlie  ye.sselsof  the  maternal  phicenta, 
iand  finally  may  pass  through  the  fcetal  i)laeenta  into  the  Ixxly  of  the 
ifcBtus.  Such  a  transmission  has  been  positively  demonstrated  in  many 
'infections  (stai)hylococcus,  streptococens,  i)nenm<)e(»eens,  tyi)h(tid  fever, 
tuberculosis,  anthrax,  smallpox,  syphili.s  and  others)  through  the  pres- 
ence of  the  nncro-(jrganisms  or  of  charaeteristie  changes  in  tlie  tissues  of 
the  foetal  organism.  In  iiiany  cases,  foi-  example,  in  1  id)erculosis  and 
{anthrax,  the  i)ath  M'hich  they  iiave  taken  may  be  demon.st rated  .since  the 
lldacenta  also  shows  characteristic  pathological  changes. 

T'p  to  very  recently  it  has  been  a.ssnmed  th:it  besides  a  placental 
transmission'there  might  occur  also  a  germtnal  transmission,  that  is, 
an  infection  of  the  sexual  cells  before  oi-  during  the  fruci  iliealion. 
Further,  it  has  also  been  taken  for  grantc<l,  fhat,  through  infection  of 
the  fi'uctifying  spermatosome,  an  infection  of  tiie  ovum  without  that  of 
the  maternal  organism  may  occur,  and  such  a  mode  of  infection  has  been 
regarded  as  established,  particularly  in  syphili.s.     TTp  to  the  ])i'esent  time 


62  PLACENTAL   TRAXS:\IISSION    OF    INFECTIOX. 

however,  this  mode  of  transmission  has  not  been  proved  by  unquestioned 
obsei-vations  to  occur  in  man  and  the  mammals,  and  its  occurrence  even 
in  syphilis  has  also  l)een  thiown  into  doubt  (Matzenauer).  According- 
to  our  present  knowledge  we  may  say  definitely  that  the  transmission  of 
infections  through  the  placenta  to  the  fcetus  in  utero  has  been  positively 
demonstrated  and  occurs  in  diiferent  infectious  diseases.  Infections  of 
the  o\-um  or  of  the  sperm  before  or  during- fructification  are  indeed  possi- 
ble, luit  it  has  not  yet  been  positively  demonstrated  in  the  case  of  man 
and  the  other  mammals  that  a  further  development  into  a  viable  lYetus  is 
possil)le  in  the  case  of  an  ovum  in  which  the  agents  of  infection  have 
produced  chai-acteristic  changes.  This  is  true  not  only  in  the  case  of 
acnte  infectious,  but  also  in  such  chronic  ones  as  tuberculosis  and  syphilis. 

According  to  the  views  of  Matzenauer,  in  no  case  of  hereditary  syphilis  can  mater- 
nal transmission  be  excluded;  and  there  are  uo  clinical  observations  that  speak  for  a 
pure  paternal  spermatic  infection  of  sj-philis.  Tlie  fact  that  the  mothers  of  children 
showing  hereditary  lues  are  immune  toward  syphilis  (Colles'  law)  cannot  be  explained 
b3Mhe  hypothesis  that  the  mother  has  received  syphilis  toxins  from  the  child  syphil- 
ized  from  the  father  and  in  consequence  has  produced  antitoxins  (Finger),  but  can  be 
explained  only  on  the  ground  that  she  herself  was  infected  with  syphilis.  That  the 
mother  often  shows  no  syphilitic  changes  cannot  be  taken  as  an  argument  against  the 
latter  view,  since  syphilis  may  often  be  present  with  complete  absence  of  symptoms. 

Literature. 

(Transmission  of  Infectious  Diseases  to  the  Fcetus.) 

Birch-Hirschfeld:  Die  Pforten  d.  placentaren  Infection  d.  Fotus.     Beit.  v.  Ziegler, 

ix.,  ISitl. 
Blumer:  Congenital  Typhoid.     Jour.  Amer.  Med.  Assn.,  xxxv. 
Charrin  et   Gley:  Rech.  sur  la  transmission    heredltaire  de   I'immunite.     Arch,  de 

l>iiys.,  vi.,  istj4. 
Condorelli:  Vaiuolo  intrauterino  in  un  feto,  Catania,  1890. 
V.  During:  Hereditiire  Syphilis.     Eulenb.  encyklop.  Jahrb.,  v.,  1895  (Lit.). 
Eberth:  Ceht  der  Typhusorganismus  auf  den  Fotus  liber ?     Fortschr.  d.  Med.,  vii., 

1SS9. 
Ehrlich:  Ueber  Immunitat  durch  Vererbung  und  Saugung.     Ztschr.   f.  Hyg.,  xii., 

1K92. 
Ernst:  Intrauterine  Typhusiafection  einer  lebensfahigen  Frucht.      Beit.  v.  Ziegler, 

viii.,  1890. 
Finger;  Die  Vererbung  der  Syphilis,  Wien,  1898  (Lit.). 
Fournier:  L'lu'redife  syphilitique,  Paris,  1891. 

Kockel  u.  Lungwitz:"Placentartuberkulose  beim  Rind.    Beit.  v.  Ziegler,  xvi.,  1894. 
Latis:  Ucberirang  des  ^lilzbrandes  von  der  Mutter  auf  den  Fotus.     Beit.  v.  Ziegler, 

X.,  isyi. 
Lubarsch:  Leber  die  intrauterine  L'ebertragung  pathogener  Bakterien.     Vircli.  Arch., 

124  P,d.,lS91. 
Maffucci:  Ueb.  d.  Verhalten  d.  Embryo  gegen  Infection.     Centralbl.  f.  allg.  Path., 

v.,  1S94. 
Malvoz:  Transmission  iuterplacentaire  des  microorganismes.     Ann.  de  I'lnst.  Past., 

isss  and  1SS9. 
Morse:   F(i!:tl  and  Infantile  Tvphoid.     Arch,  of  Ped.,  1900. 
Neumann:  Vcrcrl)ung  der  Syphili.s.     Arch.  f.  Derm.,  xxiv.,  1892. 
Porak:  I)u  passaire  des  substances  a  travers  du  placenta.     Arch,  de  med.  exp.,  1894. 
Schmorl  u.  Geipel :  Tuberkuloseder  mensch.  Placenta.    Mlinch.  med.  Woch.,  1904. 
Schmorl  u.  Kockel:  Tuberk.  der  menschl.  Placenta.    Beit.  v.  Ziegler,  xvi.,  1894. 
Straus  et  Chamberland:  Transmission   des  maladies   virul.    de  la   mere   au   foetus. 

.\n-li.  de  piiys.,  18S:!. 
Warthin:    Tuberculosis  of  the  Placenta.    Journal  of  Infectious  Diseases,  1907. 
Warthin  and  Cowie:  Tuberculosis  of  the  Placenta.    Journal  of  Infectious  Diseases, 

19114. 
Wassermann:  Erbl.  Uebertrag.  d.   Infektiouskrankh.      Ilaudb.  d.  path.  Mikroorg., 

J.-na.  19.):}. 
WolflF:  Ueber  Vererbung  von  Infectionskraukheiten.     Virch.  Arch.,  112  Bd.,  1888. 


CHAPTER  II. 

he  Spread  and  Generalization  of  Disease  through= 
out  the  Organism.  Autointoxications  and  Sec= 
ondary  Diseases. 

.  General  Considerations  Concerning  the  Spread  and  Generalization 
of  Pathological  Processes  in  the  Organism. 

;;  10.  If  through  the  action  of  any  injurious  agonl  a  local  ti.ssuc- 
liaiiiic  is  produced,  there  occurs  first  a  primary  local  disease  oi-  organ- 
isease,  which  is  accompanied  by  a  disturbance  of  function  of  the 
ffccied  part.  If  the  injurious  agent  passes  into  the  body-Juices  and 
iito  the  blood  without  causing  noticeable  changes  at  the  point  of  en- 
laiicc,  while  within  the  body  it  gives  rise  to  local  changes,  the  I'csull- 
II-  ciiudition  may  be  designated  as  a  solitary  or  nndti]>lc  lymphogenous 
I  hc'tmatogenous  local  disease  or  organ=disease. 

Local  diseases  may  during  their  entire  course  remain  confined  to  the 
i-aii  originally  affected,  yet  very  f reiiuently  they  lead  to  further  sec- 
ndary  diseases  of  organs  or  to  a  general  disease. 

Tlie_///.s/  method  hi/  irhirli  disease  processes  .s^^rwfnh  rough  out  the  body 
>  til  rough  metastasis,  by  means  of  which  there  are  very  frequently  formed, 
ot  only  solitary,  but  innumerable  foci  of  disease  throughout  the  body. 
*'ot  infre(|uently  there  may  occur  such  'd  generalization  of  disease  by  way 
f  tlic  blood  and  lymph chaunels  (tuberculosis,  suppurations,  and  cai-- 
iiiomatous  growths)  that  the  majority  of  the  organs  will  be  found  to 
oiiiain  metastases  and  show  correspondingly  more  or  less  easily  recog- 
i/i'd  functional  disturbances. 

A  second  method  of  the  spread  of  disease  occurs  in  those  diseases  in 
,  liich  in  the  primary  foci  there  are  formed  toxic  products  which,  taken 
l»  into  the  lymph  and  blood,  produce  such  changes  in  ditfei-ent  organs 
hat  they  must  be  regarded  as  intoxications  hi/  poisonous  sidtsfanees  arising 
'i-uiii  diseased  foci.  This  intoxication  is,  as  shown  in  g  12,  of  veiy  com- 
loii  occurrence  in  tlie  infections  diseases,  and  leads  not  only  to  sccondari/ 
fyriirrations  of  organs,  but  much  nu)re  to  the  i)icture  of  a  metre  or  less 
c\<re  general  disease,  as  shown  by  general  disturbances  of  metabolism, 
r\i'\\  and  disturbances  of  the  central  nervous  system. 

A  third  form  of  the  spread  of  disease  processes  throughout  tiie  body 
i((  Mines  possible  by  reason  of  the  fact  that  tlie  integiity  and  normal 
iiiictional  capacity  of  many  organs  are  to  a  great  measure  de|»<'nd<'nt 
iMMi  the  function  of  other  oi-gans ;  and,  fnrthei-,  ui)on  the  fad  that  the 
i-anism  needs,  for  the  ])reservation  of  its  normal  condition,  tiie  perfect 
niiclional  woiking  of  its  organs,  and  in  tln^  cas(^  of  many  (»rgans  cannot 
MM  iiianently  dispense  with  their  functions.  Tliere  is,  therefore,  a  large 
inn p  of  local  and  general  diseases  which  arise  as  the  result  (f  the  imperfect 
''i/iictional  activity  of  this  or  that  organ. 

63 


64  THE    GEXERALIZATIOX    OF    DISEASE. 

A  fourth  mode  of  origin  of  secondary  diseases  is  throngli  autointoxica- 
tion— tliat  is,  throngli  -^i  poisoning  of  the  organism  by  substances  ichich  arise 
in  the  body  itself  through  its  own  acticity  {metabolic poisons) .  T\iq.  place  of 
origin  of  these  snbstances  is  in  part  the  intestinal  tract  (enterogenous 
poisons),  and  partly  the  tissues  (histogenous  jwisons).  The  cause  of  the 
poisonous  action  of  these  products  of  metabolism  lies  partly  in  the  fact 
that  they  are  produced  in  an  increased  amount  or  are  retained  within  the 
body  as  a  result  of  disease  of  certain  glands ;  partly  also  that  they  are 
not  transformed  to  non-poisonous  bodies,  as  is  the  case  under  normal 
conditions.  In  conditions  of  disturbed  metabolism  poisons  foreign  to 
the  normal  body  may  be  produced. 

Affth  methodhy  which  the  animal  or  human  organism  may  be  injured 
is  the  production  of  symptoms  of  disease  through  the  impairment  and  loss 
of  function  of  those  glands  producing  an  internal  secretion  which  is  of  impor- 
tance to  the  organism.  In  this  category  belong  especially  the  thyroid, 
hypophysis,  x>ancreas,  adrenals,  liver,  and  sexual  glands.  Since  in  tlie 
disease  of  the  glands  just  named  intoxication  plays  also  an  imi^ortaut 
role,  this  group  of  processes  is  closely  connected  with  that  of  the  fourth 
mode  of  generalization  of  disease. 

II.  rietastasis  and  Embolism  and  Their  Significance  in  the  Etiology 
of  Lymphogenous  and  Haematogenous  Diseases. 

§  20.  The  transportation,  through  the  blood  or  lymph-stream,  of  a  disease- 
producing  agent,  and  the  jiroductiou  of  disease  at  the  point  of  deposit  of  such 
agent,  is  termed  metastasis.  This  is  one  of  the  most  common  modes  of  j 
the  spread  of  disease  throughout  the  body.  Ordinarily  the  term  metas- 
tasis is  applied  particularly  to  those  cases  in  which  the  transportation  of ' 
a  given  substance  is  followed  by  easily  recognizable  clinical  and  anatom- 
ical manifestations  of  disease,  especially  those  of  inflammation  or  tumor- 
foi'uiation,  so  that  we  are  accustomed  to  speak  of  metastatic  inflammations 
and  metastatic  tumors.  There  is,  however,  no  good  reason  for  not  includ- 
ing also  under  metastasis  those  cases  of  transportation  of  corpuscular 
elements  through  the  lymph  or  blood  stream  in  which  the  changes  pro- 
duced by  the  transportation  are  less  striking,  and  are  recognizable  only 
through  a  more  careful  anatomical  or  microscopical  investigation. 

The  term  metastasis  indicates  further  that  the  substance  deposited  has 
arisen  from  some  other  known  place  within  the  body.  If  the  source  of ' 
the  transported  material  is  not  known,  or  at  least  cannot  be  definitely ' 
located.  Me  are  accustomed  to  speak  of  lymphogenous  and  haematog= 
enous  deposits  and  diseases.  The  same  designation  is  also  applied  to 
dejiosits  of  known  origin. 

The  significance  of  metastasis  is  in  all  cases  dependent  upon  the 
properties  of  the  transported  body.  Insoluble  bland  foreign  bodies  of 
small  size  may  Ikia e  little  effect  upon  the  tissue;  soluble  and  chemically 
active  substances  may,  on  the  other  hand,  produce  important  tissue 
changes.  Bacteria  capable  of  reproduction  may  give  rise  to  a  disease 
which  corresponds  in  general  to  that  produced  at  the  primary  focus  of 
infection.  Tumor-cells  capable  of  growth  may  develop  into  a  secondary 
tumor.  The  size  of  the  transported  body  is  of  essential  importance  in 
hiematogenous  metastasis,  in  that  small  "bodies  may  pass  all  the  blood- 
vessels, even  the  capillaries,  while  larger  ones  will  be  carried  only 
through  those  vessels  whose  lumen  is  sufficiently  large  to  admit  them. 
AYhen  the  latter  have  by  any  means  obtained  entrance  to  the  arteries  of 


IMETASTASTS  Axn  r:ArROf.Ts:\i. 


05 


Multiple  emboli  in  the  branches  of 
Such    ^^^  pulmonary  artery,  after  thrombosis  of  the 
right  auricle,    a,  Arterial  branch ;  h,  embolus ; 


le  greater  or  lesser  circulation  and  are  carried  alon^  by  llu'  blood- 
ream,  thoy  will  become  lodged  at  those  divisions  of  the  \  esscls  where 
[le  vessel-lumen  is  too  small  to  admit  them,  and  will  llicrcby  more  or 
com])letely  obstruct  the  vessel.  This  occurrence  is  desjonati'd  by  the 
pecial  term  embolism  ;  the  body  blocking-  the  vessel  is  calk'd  an  em- 
olus  or  a  vessel=plug  (Fig.  2,  b,  c).  The  effect  of  embolism  is  in  gen- 
ral  the  more  or  less  complete  obstruction  of  the  A'cssel,  partly  throngh 
le  embolus  itself,  partly  through  an  associated  coagulation  of  the 
lood.  As  a  result  of  such  obstruction  tlicre  is  an  interference  with  the 
rculation,  which  may  vary  greatly  in  dillVrcnt  cases,  in  tiiat  behind  thi^ 
oint  of  obstruction  tliere  may  be  established  either  a  complete  or  partial 
jmpeusatory  circulation,  or  in  other 
such  a  compensation  may  be  eu- 
rely  wanting.  When  the  compensa- 
011  is  incomplete  or  wholly  absent, 
le  area  of  tissue  supplied  by  the  ob- 
ructed  vessel  undergoes  degeneration 

dies. 

Both  lymphogenous  and  hffimato- 
jnous  metastasis  usually  occur  in  the 
rectiou  of  the  normal  current,  but 
ider  special  conditions  a  transporta- 
on  in  the  opposite  direction  may  take 
ace — retrograde  metastasis. 

change  of  current  in  the  lymph-vessels    c,  embolus  with  secondary  thrombosis, 

;curs    when    the    normal    escape    of 

mph  from  the  region  involved  is  hindered  through  stoppage  of  the 
mphatics,  and  the  lymph  is  forced  to  seek  other  outlets.  A  sinular 
mditiou  may  occur  in  circumscribed  areas  of  the  peripheral  blood- 
jssels.  In  this  way  clots  arising  in  the  right  heart  or  in  the  large 
iins  of  the  body  may  be  transported  into  the  peripheral  veins;  par- 
ularly  under  conditions  in  which  there  occur  backward  waves  of 
ood  which  gradually  force  the  clots  back  into  the  smaller  veins, 
ccording  to  the  experimental  investigations  of  Arnold  upon  dogs, 
reign  bodies  (wheaten  grits),  which  were  too  large  to  pass  the  capil- 
ries,  when  introduced  into  the  jugular  or  crural  veins,  as  well  as  into 
6  longitudinal  sinus  of  the  dura  mater,  were  carried  by  retrograde 

itastasis  not  only  into  the  main  trunks,  but  also  into  tlie  smallest 
■anches  of  the  veins  of  the  liver,  kidneys,  heart,  extremities,  dura 
ater,  pia  mater,  and  orbit,  as  well  as  into  the  posterior  bronchial  veins. 

In  the  case  of  a  defect  in  the  septum  of  the  heart,  bodies  circulating 

the  blood  may  pass  directly  from  one  side  of  the  heait  to  the  other, 
d  therel)y  give  rise  to  a  crossed  or  paradoxical  embolism. 

§  21.  The  substances  which  may  be  transported  in  the  process  of 

tastasis  may  be  conveniently  di\  ided  into  six  gioni»s,  this  classili«'a- 
m  being  based  jjartly  upon  the  origin,  ])aitly  upon  the  chaiacter  of  the 
msported  body,  and  partly  upon  the  effects  of  the  metastasis. 

In  the  first  group  are  placed  insoluble  lifeless  substances  composed  of 
ry  small  particles,  which  ent<»r  the  body  fiom  withont,  and  which  may 

designated  collectively  as  dust.  The  majoiity  of  1h<-se  snbstances 
ter  the  body  in  the  respired  air,  and  jjass  fiom  the  Inngs  int(t  otiier  tis- 
es.     A  smaller  part  may  <Miter  the  tissues  directly  throngh  ac<'idental 

intentional  wounds  (tattoo).     Most  frequently  these  substances  are 
rticles  of  soot,  coal-  and  stone-dust,  moi<*  rarely  metal,  jjoicelain,  to- 
5 


66  THE    GENERALIZATION    OF    DISEASE. 

bacco,  hair  or  other  kinds  of  dust.  lu  tattooing  of  the  skin,  himpblack, 
iudia-ink,  ultramarine,  cinnabar,  and  other  granular  pigments  are  used. 
The  behavior  of  the  tissues  of  the  body  toward  such  substances  willi 
be  treated  of  elsewhere;  it  is  only  necessary  to  mention  here  that  these 
forms  of  dust,  sometimes  in  a  free  state,  sometimes  enclosed  within  cells,  ■ 
are  deposited  first  in  the  tissues  nearest  the  point  of  entrance,  further  iu' 
the  lymph- vessels  and  lymphatic  glands.  In  the  latter  location  they^ 
may  remain  for  a  life-time ;  but  in  cases  of  excessive  deposit  they  may  i 
be  carried  beyond  the  lymph-glands,  especially  in  those  instances  in 
which  the  glands,  because  of  the  great  deposit,  undergo  softening  aud'i 
give  rise  to  intiammatiou  and  proliferation  of  the  tissues  in  their  neigh- ^ 
borhood.  Very  often  as  a  result  of  such  changes  the  affected  glands  be-  i 
come  confluent  with  and  break  into  neighboring  veins.  This  event  is  es-i 
pecially  likely  to  happen  at  the  hilum  of  the  lungs,  whereby  the  contents  i 
of  the  gland  ultimately,  sometimes  slowly,  at  other  times  more  rapidly,  i 
gain  entrance  to  the  A^essel-lumen  and  are  carried  away  by  the  blood- :j 
stream.  In  the  case  of  the  lungs,  dust  may  be  deposited  directly  in  the ' 
vessel- walls  and  gradually  penetrate  as  far  as  the  intima.  Further,  the ' 
particles  from  a  broken-down  lymph-gland  can  again  enter  the  lymph-  i 
stream,  and,  if  not  again  arrested  by  some  lymphatic  gland,  may  reach  | 


Fig.  3-Fat-cmbolisiii  uf  the  lungs  (Flemming's  solution,  safranln).    a.  Arteries  filled  with  blackened 
masses  ol  fat ;  b,  fat-droplets  in  capillaries ;  c,  veins ;  d,  cells  in  the  alveoli.    X  100. 


the  blood-stream.     It  is  also  conceivable  that  softened  lymph-glands  may 
break  directly  into  the  thoracic  duct. 

As  numerous  experiments  have  shown,  the  dust  gaining  entrance  to  i 
blood-vessel  remains  but  a  very  short  time  in  the  circulation,  Larg« 
amounts  artificially  introduced  into  a  vein  disappear  in  a  few  hours  frou' 
the  circulating  blood.  The  greater  part  collects  in  the  capillaries  of  th( 
liver,  spleen,  and  bone-marrow,  partly  free  and  partly  within  leucocytes 
in  the  former  case  adhering  to  the  surface  of  the  endothelium.  After  ! 
short  time  the  leucocytes  containing  the  dust  particles  wander  out  fron 
the  vessels,  so  that  the  dust  collects  more  and  more  in  the  tissues,  when 
it  is  held  for  a  long  time,  partly  in  wandering-cells,  partly  in  fixed  cells 


METASTASIS    AXD    lOMBOLlSM.  07 

ad  partly  free,  and  under  certain  conditions  may  remain  here  during 
w  lifetime  of  tlie  individual.  In  the  mean  time  a  i)art  is  carried  in  the 
ii!l)liatics  to  other  re,t;ions  and  there  deposited,  i)articularly  in  tlu'  ])or- 
li  and  c(eliac  lynii)h-<ilands.  Accordini;-  to  the  reseai'chcs  of  Kunkcl  and 
K  licl,  still  other  cells  containin,<;'  dust-i)arti('l<'s  may  reach  the  suilacc  <»f 
ir  l)()dy-cavities,  either  throuoii  the  capillaries  of  the  lun<;s,  the  i)arcn- 
i\ ma  of  the  tonsils,  and  i)robably  also  from  the  lymi)hoid  tissue  of  the 
itcstines,  and  in  this  way  be  discharged  exteiiially.  From  the  liver  the 
list -particles  may  be  passed  out  in  the  bile.  Accordinj,^  to  observations 
ijhich  may  be  not  infrequently  made  on  inllanu'd  or<;ans,  wandering 
*  ucocj'tes  are  able  to  take  up  a  great  number  of  tlie  particles  lying  in 
le  tissues  and  transport  them  from  the  lungs,  intestinal  tiact,  and  oilier 
-ans  to  the  surface,  and  in  this  way  clear  the  tissues. 
II  The  second  group  is  composed  of  ])oitioiis  of  the  body  itself,  which 
Ji?casionally  may  be  transported  through  the  blood  sti-eani ;  namely, 
■  ssue=detritus,  parenchymatous  cells,  and  dead,  coagulated,  and 
roken=up  constituents  of  the  blood.  Of  the  elements  ai-ising  from  the 
St  ruction  of  tissue,  fat=droplets  (Fig.  3,  a,  b,  and  Fig.  4,  a,  b)  most 
ten  find  their  waj^  into  the  circulation;  particularly  when  through 
auma  or  some  other  pathological  process,  as,  for  example,  luemorrhage, 
le  tissues  are  destroj'cd.  This  occurs  most  frequently  in  cases  of  crush- 
ig,  destruction,  and  violent  agitation  of  fat-tissue,  as  may  happen  in 
le  case  of  the  different  panuiculi  adiposi  and  the  bone-nnirrow ;  but  fat 
a\'  also  enter  the  circulating  blood  through  destruction  of  li\er-tissue. 
he  parenchymatous  cells  most  frequently  entering  the  circulation  are 
■ri-cells,  syncytial  placenta- cells,  portions  of  chorionic  villi,  and  bo7ie- 
mi-oic  cells.     Ordinarily  these  are 

11  lied  into  the  pulmonary  arteries        ||?'  "^ 

1(1  capillaries,  but  through  retro-       M  ;^ 

ade     metastasis    they    may    be       Ij^^,-  ^    '%-^ 

inied into  the  veins,  and  through       ^~'        •'"'.w  •  ^*  /'rf 

iradoxical  embolism  into  the  ar-        ^/   jf^^      '\,  ^^«&3L        ^  %} 
■lies  and  capillaries  of  the  system-       '^jp    *  ^y*"^2^  Q5^#  *     '  Jl  ^ 

circulation.     Embolism  of  liver-       gv'    jV*^    ^r:y{       "'v 
■lis  and  bone-marrow  giant-cells  is         J/         V'-^^"^         ^J;.^^  'i 

msed  by  traumatic  and  toxic  in-        p^',  •  ,  f 

I  lies    and    htemorrhages  of    the       j^',  A 

t'ected    tissues.       Placental  -  cell       %i^^  ,  .^ 

iiboli,   in  the  form   of   syncytial        „     ,1..,     .1        r..    >  < 

'  '        •  Fig.  4.— tat-eiiibolisiauf  the  kiiiiit'v  iHciiiming's 

ant  -  cells,      have    been    observed       solution,  safranin).    a,  (iloniemli  wltli  fat  in  the 
pecially  in    puerperal    eclampsia,        capillaries:  ^fat-dropIet.  in  tl-eintmubularca 

It    occur   also   in  the   course   of 

niiial  pregnancies.  Pulmonary  emboli  of  small  portions  of  the  cin.ri- 
lic  villi  havealso  been  observed!^  In  diseased  conditionsof  the  intima  of 
ic  heart  or  blood-vessels,  degenerated  endothelium,  broken-down  and  degen- 
•"fed  masses  of  connective  tissue  of  the  intima,  2>ortions  of  the  indves,  and 
alerial  of  similar  nature  may  gain  entrance  to  the  l)lood-stream.  Frag- 
riif.s  and  disintegrated  portions  of  bloodcorpusrlfs  m:iy  vnii^v  i\u'  vUTuhi- 
011  from  luemorrhagic  foci  or  may  aiise  Nvithin  the  vessels  themselves, 
1  the  case  of  degenerative  chang<*s  produced  in  the  blood  through  the 
illnence  of  various  harmful  agents.  Coagulated  niassrs  (f  Idood  vntcr 
K'  circulation  when  a  thrombus — i.e.,  blood  coagulated  in  th«?  vessels 
ce  Chapter  IV.) — breaks  loose,  either  in  toto  or  in  fragments. 
The  fate  of  the  last-named  substances  is  for  the  chief  part  dependent 


68  THE    GENERALIZATION    OF    DISEASE. 

Tipou  their  size  and  physical  properties.  All  fragments  of  much  greate 
diameter  than  tlie  lumen  of  the  capillaries  become  lodged  in  the  bifurca 
tious  of  the  arteries  (Fig.  2,  a,  b)  and  nsually  occlude  the  same.  This 
occurs  most  frequently  in  the  case  of  dislodged  thrombi  or  of  fragmeiife 
of  such  ;  on  the  other  hand,  fat-droplets  usually  pass  into  the  capillaries; 
where  part  remain,  while  others  pass  through  and  later  become  lodged  lE 
some  other  place.  Since  the  fat  occasionally  passes  first  into  the  veina 
of  the  body  and  thence  to  the  heart,  the  fat-droplets  collect  especiallj 
in  the  capillaries  of  the  lungs  (Fig.  3,  b) ;  but  they  may  also  pass  througl 
the  lungs  into  the  capillaries  of  the  greater  circulation,  and  are  thei 
found  especialh'  in  the  intertubular  and  glomerular  capillaries  of  th^ 
kidneys  (Fig.  4,  a,  b),  and  also  to  some  extent  in  the  capillaries  of  othe* 
organs.  Capillary  fat-embolism  causes  a  noticeable  disturbance  of  tht 
circulation  only  when  of  extensive  occurrence ;  in  this  case  it  may  lead 
to  the  production  of  cedema  of  the  lungs.  Furthermore,  the  fat  disap- 
pears in  the  j)rogress  of  metabolism,  or  is  conveyed  into  the  neighboring 
tissues. 

Parenchymatous  cells  (in  so  far  as  the  entrance  into  the  circulatioii 
of  small  living  cells  of  the  character  of  lymphocytes  and  myelocytes  is 
not  concerned)  become  lodged  in  the  capillaries  or  smaller  arteries  Id 
the  case  of  arterial  metastasis.  The  latter  is  especially  true  of  liver-cells 
when  entering  the  circulation  en  masse.  At  the  place  of  lodgment  theii 
presence  may  lead  to  a  heaping-uj)  of  blood-plates  and  a  hyaline  coagula- 
tion. The  cells  themselves  do  not  multiply,  but  they  may  remain  pre^ 
served  for  a  certain  length  of  time,  according  to  Lubarsch,  as  long  as 
three  weeks.  They  then  gradually  die,  the  protoplasm  dissolves,  the 
nuclei  swell  or  shrink,  and  finally  lose  their  chromatin. 

The  point  of  lodgment  of  loosened  thrombi  or  fragments  of  thrombi 
depends  upon  the  path  which  they  take,  as  well  as  upon  their  size.; 
Since  thrombi  may  be  formed  in  the  systemic  veins,  right  heart,  and' 
pulmonary  arteries,  as  well  as  in  the  pulmonary  veins,  left  heart,  and! 
systemic  arteries  (see  Chapter  IV.),  it  is  possible  for  embolism  to  occur 
in  any  of  the  arteries  of  the  greater  or  lesser  circulation.  Very  often 
the  emboli  lodge  at  the  bifurcation  of  arteries,  forming  the  so-called 
riding  or  straddling  emboli  (Fig.  2,  c).  Through  retrograde  metastasis 
emboli  may  be  carried  from  the  venie  cavte  or  larger  veins  into  the, 
smaller  veins.  Defects  in  the  septum  of  the  heart  may  lead  to  the  pro- 
duction of  a  paradoxical  embolism. 

Small  fragments  of  thrombi,  dead  red  blood-cells  or  fragments  of: 
such,  endothelial  cells  undergoing  disintegration  or  fatty  degeneration,  \ 
etc.,  meet  the  same  fate  as  dust-particles.  They  may  remain  free  or  be 
taken  up  by  cells;  they  are  soon  removed  from  the  circulation  and  col-' 
lect  especially  in  the  spleen,  liver,  and  bone-marrow,  where  they  uu-' 
dergo  f uither  changes  and  are  destroyed.  The  products  resulting  from; 
the  destru(;tion  of  red  blood-cells  may  persist  for  a  long  time  in  the  or-ij 
gans  named,  as  colored  deposits. 

Tlie  thiid  group  of  substances  producing  metastases  is  composed  of 
living  cells,  which,  originating  from  proliferating  tissue=foci  and  hav- 
ing gained  entrance  to  the  circulation  through  direct  rupture  into  the 
blood-vessels,  or  having  entered  the  lymphatics,  are  carrried  to  other  or- 
gans. This  process  may  be  observed  in  the  case  of  tumors  growing  by 
infiltration.  The  metastasis  of  living  cells  from  such  a  tumor  leads! 
through  the  proliferation  of  the  transported  tumor-cells  to  the  produc- 
tion of  metastatic  daughter-tumors,  which  in  the  case  of  lymphogenous 


METASTASIS    AM)    K.MIJOLIS.M.  ()<) 

iMiastasis  develop  liist  in  the  lymph- vessels  and  lyniph-olaiids,  b\it  in 
In  case  of  direct  ru])tnre  int.  tlie  blood-vessels  arise  in  that  i)ait  of  llir 
i-ciilar  system  to  which  the  tumoreells  are  carried  by  tlie  bh)od.  Tlie 
11,  lastasis  usually  occurs  in  the  normal  direction  of  the  blood-  and  lympli- 
, I  reams,  but  rrtrof/nide  fnoisporfation  may  also  occui-,  thereby  ai  tumor 
jiliich  has  broken  into  one  of  the  systemic  veins  may  jrive  lise  to  melas- 
ases  in  the  region  drained  by  smaller  branches  of  other  systemic  veins, 
ifirograde  metastasis  is  not  iutre({ueutly  obser\cd  in  the  lymphatic  sys- 
iin,  when  closure  of  the  etferent  lymph-channels  has  produced  a  change 
II  I  he  direction  of  the  lyinph-cnrrcut. 

In  the  fourth  group  nuiy  be  placed  all  those  processes  charactcii/.cd 
.y  the  entiauce  of  vegetable  or  animal  parasites  into  the  circulation. 
t  under  such  circumstances  these  oiganisms  do  not  liud  conditions  suit- 
1)1('  for  their  development,  they  are  (piicUly  eliminated  from  th<>  blood- 
i!vam  and  desti'oyed  under  the  iiilbK-nce  of  metabolic  pr(»cesses.  Iliit 
iliey  are  able  to  repr(Mluce  tluMuselves  anywhere,  they  will  gixc  lise  to 
\\v  ])roduction  of  metastatic  foci  of  infection,  which  are  located  partly 
1  the  vascular  system,  but  also  partly  extending  thence  into  the  neigh- 
Miing  tissues.  The  secondary  foci  in  the  case  of  bacterial  invasion 
:i\t'  in  general  the  same  character  as  that  of  the  primary.  If  an  em- 
iilus  contains  organisms  capable  of  producing  tissue-necrosis,  inflam- 
lation,  and  pntrid  decomposition,  there  will  occur,  along  Avith  the 
iiiliolism  and  the  accompanying  disturbances  of  circulation,  suppuration 
ii»i  sloughing — that  is,  there  will  be  a  repetition  of  the  same  processes 
i(  urriug  at  the  original  seat  of  infection. 

As  the  fifth  group  of  metastatic  i)iocesses  maybe  classed  togellicr 

lose  cases  in  which  constituents  of  the  human  body   having  under- 

jone  solution  are  transported  in  the  soluble  state  and  again  deposited 

ri  a  solid  form  ;  and   also  those  in  which   extrinsic  substances   are 

aken  up  by  the  body  in  a  soluble  form  and  are  then  deposited  in  the 

ssues  in  a  solid  state.     Of  the  tirst  class  there  occurs  most  ficcpiently 

ic  entrance  of  bile-pigment  into  the  circulation  Mithintlu^  liver,  so  that 

lis  may  permeate  thrcAigh  the  most  varied  tissues,  an<l  give  to  them  a 

illowish   color   (icten(s).      N^ot   infrequently    iron-coniainiiif/  (1('rir(itiiy:<< 

■  i sing  from  the  destruction  of  red  bJood-eells  in  the  cirenJafion  are  carried  to 

H-  si)leen,  bone-marrow,  liver,  and  kidneys  and  form  there  ])athological 

posits  of  iron  (htematogenous  siderosis).     Fat  can  be  split  off  froi.n  the 

It  <lep6ts  in  the  form  of  soluble  soaps  and  cari-ied  through  the  blood  to 

iricrent  organs  where  it  is  again  taken  up  by  the  cells  and  changed  into 

Mitral  fat. 

When  preparations  of  silver  are,  for  medicinal  purposes,  introduced 
It  o  the  body  through  the  ga.stro-intestinal  ti-act  for  long  periods  of  time, 
lire  may  occur  a  deposit  of  fine  f/mnrdes  of  silrer  in  the  connectivi;  tis- 
H-  of  the  skin,  in  the  glomeruli,  medullary  ])yiamids  of  the  kidu<'ys. 
itima  of  the  large  arteries,  adventitia  of  thesjuall  arteries,  in  the  neigh- 
M-hood  of  mucous  glands,  connective  tissue  of  the  intestinal  villi,  in  the 
loioid  jdexus  of  tlie  cerebral  ventricles,  and  in  the  serous  membranes. 
i-^ncs  showing  such  a  dej^osit  l^ne  a  grayish-bi-own  coloi-. 

the  fact  that  the  epithelial  tissu<'s  and  the  brain  are  not  alfected 
M'ws  that  there  is  a  selective  action  on  the  i)art  of  the  l issues,  and  that 
11^  selective  action  differs  essentially  from  that  which  is  sc.-n  in  the  case 
a  metastatic  deposit  of  corpuscular  elements.  It  may  theretoir  be  as- 
iiiicd  that  the  cheinico-physical  character  and  tlu;  functional  activity  of 
'   tissues  coming  into  contact  with  substances  in  solution  <'xeii  a  deter- 


70  THE    GENERALIZATION    OF   DISEASE. 

miiiiii<^  iufluence  upon  the  separation  and  j)recipitatiou  of  such  sui 
stances. 

As  a  sixth  "roup  of  metastatic  processes  may  be  classed  the  entrant 
of  air  into  the  circulation.  If  in  any  manner  a  large  amount  of  a 
gains  entrance  to  the  right  heart,  an  event  which  occurs  especial! 
in  case  of  injury  to  the  large  veins  lying  in  the  neighborhood  of  tl 
thoracic  cavity,  or  more  rarely  from  the  oi^ening  of  a  vein,  for  exampi 
of  a  stomach-vein,  through  ulcerative  processes,  the  air  mingling  wit 
the  blood  forms  a  foamy  mass,  which  the  contractions  of  the  heart  ai 
scarcely  able  to  drive  onward.  As  a  result  the  left  heart  receives  littj 
or  no  blood,  the  aortic  pressure  falls,  and  the  aif ected  individual  quickl 
dies.  Should  the  air  enter  the  circulation  in  small  amounts  or  intermi 
teutly,  it  may  be  carried  by  the  blood-stream  in  form  of  air-bubbles  an 
circulate  through  the  entire  body.  Larger  amounts  may  lodge  for  a  tin 
in  the  vessels  of  the  major  or  minor  circulation,  obstruct  their  lumei 
and  cause  disturbances  of  the  circulation,  which  may  give  rise  to  funi 
tional  disturbances  of  the  brain  and  respiration.  If  these  conditions  c 
not  cause  death,  the  air  is  after  a  time  absorbed. 

If  the  lung-tissue  be  ruptured  through  trauma  or  through  violei 
coughing,  screaming,  or  vomiting,  etc.,  air  may  be  forced  into  the  coi 
nective=tissue  spaces  and  lymphatics,  and  may  extend  through  thei 
into  all  parts  of  the  lungs,  pleurte,  and  the  mediastinum,  as  well  as  in 
the  skin.  The  conditions  thus  produced  are  termed  emphysema  of  tl 
skin,  of  the  subcutaneous  tissue,  of  the  mediastinum,  etc.  Under  cei 
tain  circumstances  the  air  may  spread  through  a  large  area  of  the  sul 
cutaneous  lymph-vessels  and  connective-tissue  spaces,  whereby  the  ski 
presents  an  inflated  appearance  and  when  pressed  upon  produces 
crackling  sound. 

According  to  Siebel  and  Kiinkel,  granules  of  cinnabar  and  indigo  injected  into  tl 
blood-stream  of  a  frog  are  quickly  taken  up  by  leucocytes,  and  after  one  to  two  houj 
no  more  free  granules  are  to  be  found  in  the  circulating  blood.  After  twenty-fo'! 
hours  the  leucocytes  containing  pigment-gi'anules  have  disappeared  from  the  circulj 
tion,  and  lie  for  the  greater  part  clumped  together  in  the  cajiillaries,  the  greatest  nui; 
bers  being  found  in  the  capillaries  of  llie  spleen,  liver,  bone-marrow,  and  the  lung' 
while  they  occur  in  smaller  numbeis  in  the  capillaries  of  the  kidneys,  and  in  still  small' 
numbers  in  the  capillaries  of  the  heart  muscle. 

Even  after  two  hours  free  pigment  and  cells  containing  granules  are  found  outsii 
of  the  vessels,  and  after  a  few  days  they  have  almost  wholly  disappeared  from  the  vt 
sels.  The  granules  lie  then  partly  in  wandering-cells,  partly  in  fixed  cells,  as  well 
in  the  free  cells  of  the  splenic  pulp  (JV>///?cA;)  and  bone-marrow.  They  may  be  foui 
in  these  organs  for  weeks  afterward  {Hoffmann,  Langerhans).  In  both  frogs  and  do 
some  of  the  granule-containing  cells  find  their  way  into  the  lumen  of  the  alveoli  ai 
bronchioles  and  so  pass  out  of  the  body.  In  the  liver  the  pigment-particles  for  t 
greater  part  adhere  for  a  short  time  to  the  endothelium  of  the  liver-capillaries  a 
may  be  taken  up  by  the  endothelial  cells  (  Browicz,  Heinz)  ;  another  part  is  found 
leucocytes,  which  later  wander  out  from  the  vessels  into  the  tissues.  Thence  they  a 
for  the  greater  part  taken  up  into  the  lymphatics  of  the  liver  and  ultimately  reach  t 
lymi)h-glan(ls.  A  part  of  the  granules  finally  pass  out  with  the  bile,  but  by  whi 
course  tliey  reach  the  bile-vessels  is  not  known.  lu  dogs  the  pigment-granules  aK 
collect  in  the  tonsils  and  are  carried  to  the  surface  through  the  epithelium  by  ti 
leucocytes  which  have  taken  them  up.  j 

According   to  the    observations    of    Jadassohn   ("Pigmeutverschleppung  aus  d! 
Haut, "  Arrh.f.  Derm. ,  24  Bd. ,  1892)  and  Sclimorl  ("  Pigmeutverschleppung  aus  der  Haul 
Centmlld.  f.  allg.  Path.,  4Bd.,  1893),  both  normal  and  pathological  pigment  may 
transi)orted  from  the  skin  to  the  lymph-glands — in  other  words,  a.  pignient-metasUv 
may  take  place. 

According  to  LeiC!in{Arch.  f.  exp.  Path.,  40  Bd.,  1897),  if  the  outflow  of  urine  frc 
the  bladder  be  hindered,  small  foreign  bodies  can  pass  into  the  kidney-pelves,  ai 
thence  into  the  urinary  tubules,  lymph-vessels,  and  veins,  and  into  the  general  circul 
tion. 


METASTASIS    AXT^    KM  I{(  )1.1S.M.  71 

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1SU3. 
Beneke:  Fettembolie.     Beitr.  v.  Ziegler,  xxii.,  1897. 
Colley:  Fettembolie  nach  gewaltsamer  Gelenkbeugung.     Zeitschr.  f.  Chir.,  36  Bd., 

1893. 
Ebstein:  Lipiimie  u.  Fettembolie  bei  Diabetes.     Virch.  Arch.,  155  Bd.,  1899. 
Flournoy :  Contrib.  a  I'etude  de  rembolie  graisseuse,  Strassburg.  1878. 
Graham:  Fat  Embolism.    Jour,  of  Med.  Research,  1907. 
Haemig-:  Fettembolie  des  Gehirns.     Beitr.  v.  Bruns,  27  Bd..  1900. 
Hamilton:  Lip;emia  and  Fat  Embolism.     Edinburgh  Med.  Journal.  1879. 
Hess:  Beitr.  z.  d.  Lehrc  v.  d.  traumatischeu  Leberrupturen.     Virch.   Arch.,  121  Bd., 

189(1. 
Jiirgens:  Fettembolie  u.  Metastase  v.  Leberzellen.     Tagebl.  d.  Xaturf.-Vers.  in  Ber- 
lin, 1886. 
Klebs:  Multiple  Lel)erzelleuthrombose.     Beitriige  v.  Ziegler,  iii.,  1888. 
Leusden:  Puerperale  Eklampsie.     Virch.  Arch.,  142  Bd.,  1895. 
Lubarsch:   Parenchymzellenembolie.     Fortschr.  d.  Med.,  xi.,  1893;   Zur  Lehre  von 

den  Geschwiilsten  u.  Infectionskranklieiten,  Wiesbaden,  1899. 
Maximow:  Parenchymzellenembolie.     Virch.  Arch.,  151  Bd.,  1898. 
V.  Recklinghausen:  Allgem.  Pathologic  d.  Kreislaufs,  Stuttgait,  1883. 
Ribbert:  Fntcmbolie.     Correspbl.  f.  Schweizer  Aerzte,  1894. 
Schmorl:   Kinljol.  Ver.schleppung  v.  Lebergewebc.     Dent.  Arch.  f.  klin.  Med..  42  Bd., 

isss;  ()iM,-inbefunde  bei  Eklampsie.     Cent.  f.  allg.  Patii.,  ii. ;  Unters.  tib.  Puerpe- 

ralcklampsie,  Leipzic,  1893. 
Scriba;  Fettembolie.     Deut.  Zeitschr.  f.  Chir.,  1879. 

Turner:  Hepatic  Cells  in  the  Blood.     Trans,  of  the  Path.  «oc.  of  London,  1884, 
'  Virchow:  Berl.  klin.  Woch.,  1886,  No.  30;  Virch.  Arch.,  5  Bd. ;  Ges.  Abhandlungen, 

IWarthi'n:  Pulmonary  Emboli   of    Liver-cells  and    Bone-marrow   Giant-cells.     Med. 

^  Zenker  :''schussverletzung  d.  Leber  mit  Versehleppung  v.  Lebcrgewebe.  Deut.  Arch. 
f.  klin.  Med.,  42  Bd.,  1888. 


72  THE    GENERALIZATION    OF    DISEASE. 

{Betrograde  and  Paradoxical  Metastasis.) 

Arnold:  Ueber  liicklaufigen  Transport.    Vircb.  Arch.,  124  Bd.,  1891. 

Bonome :  Trasporto  retrograde  degli  emboli  e  embolia  crociata.     Arch,    per  le   Sc 

Med.,  xiii.,  1889. 
Bouma:  Retrograder  Transport  im  Yenensystem.    Virch.  Arch.,  171  Bd.,  1903. 
Cohn:  Klinik  der  enibolischen  Gefasskrankheiten,  Berlin,  1860. 
CohnheiiTi:  Vorlesungen  liber  allgemeine  Pathologic,  Berlin,  1882. 
Ernst:  Rlicklauf.  Transport  in  Herz- n.  Lebervenen.    Virch.  Arch.,  151  Bd.,  1898. 
Hauser:    Enibol.    Verscldeppung   v.  Thromben  a.   d.  r.  Herzen   in   Korperarterien 

Mliuch.  med.  Woch.,  1888. 
Lui:  Due  casi  di  embolia  retrograda.     Arch.    p.  le  Sc.  Med.,  xviii.,  1894. 
V.  Recklinghausen:   Venose  Embolic  u.  retrograder  Transport.     Virch.  Arch.,  100 

Bd.,  1885. 
Ribbert:  Retrograder  Transport  im  Venensystem.     Cbl.  f.  allg.  Path.,  1897. 
Schmorl:  Leberruptiir  mit  embol.  Verschleppung  v.  Lebergewebe.     Deut.  Arch.  f. 

klin.  ]Med.,  42Bd.,  1888. 
Vierth:  Riicklaulige  Metast.  in  den  Lymphbahnen.     Beitr.  v.  Ziegler,  xviii.,  1895. 
Vog-el:  Retrograde  Metastase  innerh.  d.  Lj'mphbahn.     Virch.  Arcli.,  125  Bd.,  1891. 
Zahn:   Paradoxe  Embolic.      Virch.  Arch.,   115  Bd.,  1889;  Geschwulstmetastase,  ib., 

117  Bd.,  1890. 

{Air  Embolism.) 

Couty :  Etude  exper.  sur  I'entree  de  I'air  dans  les  veines.     Gaz.  med.  de  Paris,  1876. 
Bamsch:    Ueber  Unterhautemphysem  bei  Bronchopneumonie.      Deut.  med.  Woch., 

1891. 
Fischer:  Luftcintritt  in  die  Veuen  wahrend  einer  Operation.     Deut.   Chir.,  Lief.  18, 

1885. 
Frantzel:  Unterhautemphysem  bei  Erkrank.  d.  Respirationsapparates.     Deut.  med. 

Woch.,  1885. 
Hare:  Entrance  of  Air  into  Veins.     Therapeutic  Gaz.,  1889;  Amer.  Jour,  of  Med  Sc, 

1902. 
Hauer:    Erscheiniingen  im  gr.  n.   kl.  Kreislauf  bei  Luftembolie.     Zeit.  f.  Ileilk.    xi 

1890. 
Heller,  Mager,  u.  v.  Schrotter:  Arterielle  Luftembolie.     Zeit.  f.  klin.  ]Med.,3'3  Bd., 

isitr. 

Huseniann:  Luftembolie.     Eulenburg's  Jahrb.,  viii.,  1899. 

Jlirgensen:  Luftcintritt  in  d.  Venen.     Deut.   Arch.   f.   klin.  Med.,  31  Bd.  ;  Luft  im 

Blute.  il).,  41  r>(l..  1887. 
Panum:  Exper.  Beitriige  zur  Lehre  von  der  Embolic.     Virch.  Arch.,  25  Bd.,  1862. 
Passet:  Ueber  Luftcintritt  in  die  Venen.     Arbeiten  a.  d.  path.  Institut  zu  Munchen, 

1886. 
Senn:  Entrance  of  Air  into  Veins.     Trans.  Amer.  Surg.  Assn.,  1885. 
Wolf:   Luftembolir'.     Virch.  Arch.,  174  Bd.,  1903. 


HI.  The  Sequelae  of  Local  Organic  Disease. 

§  22.  Secondary  diseases  which  arise  as  the  results  of  patho= 
logical  conditions  of  individual  organs  occur  with  great  froqiieiicy  as 
the  result  oi  pathological  changes  in  the  blood  and  circulatonj  apparatus. 

The  circulatoi-y  apparatus  and  the  blood  therein  contained  bear  cer 
tain  relations  to  all  the  body-tissues,  and  accordingly  diminution  in  i 
amount  -Mid  pathological  alterations  of  the  blood,  as  well  as  changes  in  the  i 
blood-vessels,  often  give  rise  to  diseased  conditions  of  this  or  that  tissue 
or  of  the  entire  organism.  If  the  hsemoglobin-content  of  the  blood  is 
decreased  thi'ough  a  diminution  in  number  of  the  red  blood-cells 
(oligocytluciiiia),  oi-  thiough  a  pathological  condition  of  the  same,  or  if 
the  lui'moglobin  through  the  action  of  carbon  monoxide  is  rendered  in- 
capable of  taking  up  the  oxygen  of  the  air,  the  body-tissues  will  no 
longer  receive  a  normal  amount  of  oxygen ;  consequently  there  will  arise, 
in  case  the  amount  of  oxygenation  falls  below  a  certain  point,  disturb- 


THE    SEQUEL,^    OF    LOCAL.   DLSEASES.  7'^ 

^ances  of  nutrition,  ns  the  results  of  wliicli  IIumc  occui- Ncry  frciiucntly 
conditions  of  fatty  doooueration,  and  under  certain  oircuinstances  dcatii 
Ithrough  jiaralysis  of  the  nervous  centres. 

Should  0)1  artenj  become  narroired  or  closed  through  Ihromhonis  or  em- 
holism,  or  ihickenings  of  its  iratls,  as  in  the  case  of  the  ailerial  disease 
known  as  arteriosclerosis,  there  will  arise  in  the  region  su{)plied  by  the 
ififected  vessel  a  h^cal  deliciency  of  food-supi)ly  and  oxygen,  local  as- 
phi/.via,  and  later  degenerative  liroeesses,  which  frequently  end  in  tlu^ 
,leath  of  the  specific  parenchymatous  elements,  at  times  also  of  the  con- 
I lective-tissue  framework. 

In  the  brain  and  spinal  cord  tlie  vessel -changes  lead  to  ischa-mic  proc- 
i^sses  of  softening,  which  frequently  result  in  paralysis,  and  not  rai-ely 
In  death.  In  the  heart  there  results  a  diffuse  fatty  degeneration  or  local 
[softening  of  the  heart-muscle,  giving  rise  to  disturbances  of  cardiac  ac- 
livity  or  often  even  to  complete  insutticiency.  In  the  kidneys  the  secret- 
jng  glandular  parenchyma,  together  with  a  portion  of  the  connective 
issue,  undergoes  necrosis  or  atrophy;  and  the  loss  of  these  substances 
iives  rise  to  local  or  widespread  contractions,  which,  accoiding  to  their 
)rigin,  are  designated  as  embolic  or  arteriosclerotic  atroidiies. 

In  the  stomach  ischnemia  of  the  mucous  mend)ianes  gixes  rise  to  local 
dcerations;  in  the  liver  and  muscles  to  atrophic  conditions.  Xo  tissue 
an  withstand  the  harmful  effects  of  a  long-continued  ana'inia,  and  con- 
equently  the  narrowing  and  closure  of  arteries,  through  the  formation 
f  clots  or  through  changes  in  the  vessel-walls,  play  a  very  important 
ole  in  pathology ;  and  are  not  only  the  causes  of  anwmic  necrosis  (see 
hapter  V.)  and  hemorrhagic  infarction  (see  Chapter  IV.),  but  also  of 
lumerous  i^rogressive  atrophies  of  organs.  In  the  pathogenesis  of  the  last 
lamed,  arteriosclerosis  has  an  esi^ecially  important  part,  since  in  old 
ge  it  is  of  very  common  occurrence,  and  gives  rise  to  tissue-degenera- 
ions  in  organs  of  the  most  different  structure.  As  evidences  of  such 
legenerative  processes,  the  majority  of  the  affected  organs  show  later 
reas  of  scar-tissue,  in  which  the  specific  parenchyma  has  disai)peared 
'hile  the  connective  tissue  has  increased. 

The  active  participation  of  the  vascular  apparatus  in  all  injlamma- 
in/ processes  (i>ee  Chapter  YIL),  the  distnrhanee  <f  circulation  thi-ough 
he  alteration  of  the  vessel-walls,  the  shifting  and  changes  (f  the  raseular 
hnnnels  which  result  fi'om  the  closure  of  old  vessels  hi/ proliferation  (f  en- 
of helium  or  through  thrombosis,  as  well  as  from  the  formation  <f  nrw 
fssrls,  make  easily  comprehensible  the  fact  that  in  all  chronic  inllamma- 
iMiis  the  specific  cells  dependent  upon  a  regulated  nutrition  undergo 
•  ueneration  and  are  frequently  rei)laced  by  connective  tissue  of  a  lower 
I  ade  than  normal. 

A  profuse  watery  discharge  from  the  intestines  may  deprive  the  or- 

auism  of  water.     If,  as  a  result  of  stenosis  of  the  (esophagus  or  pylorus, 

sutfic'.ent  amount  of  food  is  prevented  from  entering  the  intestinal 

I  act,  or  if  the  stomach  and  intestine  are  no  longer  able  to  digest  tiie 
Hid  brought  to  them  and  to  prepare  it  for  assimilation  into  the  i>ody 

I I  ices,  the  organism  as  a  whole  becomes  poorer  in  albumin  and  fat. 

If  the  heart  is  no  longer  able  to  force  onward  with  normal  strength 
le  blood  coming  to  it,  there  will  arise  in  various  organs  ehanges  due.  to 
eiious  stasis.  U  the  respiration  is  hindered  or  imixMlect,  the  eomitosi- 
lon  of  the  blood  suffers  changes.  Collection  of  lliiid  in  the  tlioiaeic 
ivity  causes  compression  of  the  lungs;  interference  with  expiration, 
ith'^free  inspiration,  leads  first  to  distention  of  the  lung  and  later  to 


74  THE    GEXERALIZATIOX    OF    DISEASE. 

atrophy.  If  a  part  of  the  Jung  has  been  rendered  useless  by  chronic  i; 
flammation,  the  inspiratory  enlargement  of  the  thorax  affects  only  th: 
portion  of  the  Inng  which  is  capable  of  f  nnctionating,  and  this  part  b 
comes  over-distended  and  in  consequence  finally  atrophic. 

Diseases  of  the  parenchyma  of  the  liver  often  give  rise  to  disturbanc 
of  the  circulation  of  blood  through  the  organ,  and  stasis  throughout  tl 
portal  circnlation  with  resulting  ascites.  Should  the  xxincreas  be  d 
stroyed  or  if  it  is  no  longer  able  to  produce  its  ferments  (proteolyt 
trypsin,  amylolytic  diastase,  and  the  fat-splitting  and  emulsifying  stea 
sin)  there  results  an  imperfect  metabolism  of  albumin,  carbohydrate 
and  fat. 

Hindrance  to  the  outflow  of  urine  from  the  ureters  renders  difficult  tl 
secretion  of  the  kidneys  and  leads  to  their  atrophy.     The  loss  of  a  Jar 
portion  of  the  renal  parenchyma  is  followed  by  increased  blood-pressure 
the  aorta,  increased  action  of  the  heart,  and  hypertrophy  of  that  orga 

An  increased  resistance  in  the  pulmonari)  circulation  due  to  diseased  co 
ditions  of  the  lungs  is  often  followed  by  dilatation  and  hypertrophy 
the  right  heart.  Obstruction  to  the  Jiow  of  blood  through  the  aortic  open i 
leads  to  hypertrophy  of  the  left  ventricle.  Stenosis  and  insufficiency 
the  mitral  valve  cause  a  stasis  of  blood  backward  through  the  lungs 
the  right  heart.  This  may  be  compensated  for  through  hypertrophy 
the  right  ventricle,  or  may  extend  farther  back  into  the  veins  of  the  sj 
temic  circulation. 

An  obUque  position  of  the  pelvis  leads  to  curvature  of  the  spine.  SVi 
ness  and  immovability  of  a  joint  cause  atrophy  of  the  muscles  moving  ti 
joint,  the  atrophy  being  due  to  inactivity. 

Diseases  of  the  nervous  system  may  give  rise  to  functional  disturbanc 
and  anatomical  changes  in  any  organ  of  the  body — in  glands,  musck 
skin,  bones,  lung,  heart,  intestine,  etc.     These  changes  are  to  be  referrc 
partly  to  stimulation,  partly  to  inhibition  or  arrest  of  nervous  impulse 
and  partly  to  ansesthesia  (anaesthetic  tissues  being  especially  liable  to  i 
jury).     Destruction  of  the  large  ganglion-cells  in  the  anterior  horns  of  t" 
spinal  cord  leads  to  the  atrophy  of  the  corresjDonding  peripheral  nerv 
and  muscles.     Paralyzed  extremities  become  atrophic.     Diseased  conr 
tions  in  the  region  of  the  respiratory  and  vasomotor  centres  lead  to  d: 
turbances  of  respiration  and  circulation.     After  injury  to  certain  pc, 
tions  of  the  medulla  oblongata,  after  concussion  of  the  brain  and  spin; 
cord,  through  the  presence  of  tumors  in  the  brain,  after  psychical  affe 
tions,  after  poisoning  of  the  nervous  system,  there  is  caused  under  certa 
conditions  a  rapid  withdrawal  of  the  glycogen  of  the  liver  into  the  bloo 
stream  and  the  excretion  of  sugar  in  the  urine.     Stimulation  of  perip 
eral  ner\es  may  produce  abnormal  reflex  sensations  and  movements 
well  as  circulatory  disturbances  in  other  parts  of  the  body.     Paralyf 
of  both  vagi  or  of  their  branches,  the  recurrent  laryngeal  nerves,  throu, 
inflammatory  changes  or    through  pressure  from  neighboring  lymj) 
glands,  etc.,  may  be  followed  by  inflammation  of  the  lungs,  in  that  t 
accompanying  paralysis  of  the  laryngeal  muscles  favors  the  entrance 
foreign  bodies  into  the  lungs  during  inspiration. 

The  so-called  trophoneurotic  diseases  of  ttie  tissues  are  not  mentioned  above, 
the  reason  that  the  trophic  relations  of  the  nervous  system  to  the  individual  tissues  : 
not  yet  clear,  and  the  views  of  dillereut  authors  as  to' the  dependence  of  the  tissues  up 
the  nervous  system  vary  greatly.  Many  authors  ascribe  to  the  trophic  action  of  1  • 
nervous  system  a  far-reaching  influence  upon  the  conditions  of  tlie  tissues,  and  seek  t 
nerves  fornuug  the  connections  with  the  nerve-centres,  partly  in  the  motor,  secretoi 


AI'TOI  XTOX IC  ATI  O  X .  75 

ami  reflpx  nerves,  as  woll  as  in  sjiccial  tnijihic  nerves.  Thus,  for  example, 
muscular  atiopliy.  i;landular  atrophy,  atrophy  of  tlie  bones  and  joints  (in  tahes  and 
syringomyelia),  diHerent  pathological  conditions  of  the  skin  diaraeteri/ed  by  tliinning, 
exfoliation  of  the  epithelium,  loss  of  liair,  intlammations,  etc..  unilateral  tissue- 
atrophies,  necroses,  also  hypertropliic  i)roliferations  of  muscles,  ghinds,  .skin,  or  l^ones, 
etc.,  are  all  referred  to  allectious  of  the  nerves. 

It  cannot  be  doubted  that  both  degenerative  and  liypertrojihic  tissue-changes  and 
inflammations  often  occur  as  sequelaMo  disturbances  ()f  innervation,  but  these  most 
probably  are  not  the  direct  result  of  the  removal  or  change  of  nerveinlluences  alTecting 
the  tissues,  but  are  rather  the  results  of  increased  or  decreased  functional  activity  of 
the  tissue,  or  of  injuries,  inflammations,  or  disturbances  of  circulation,  which  have  de- 
veloped in  connection  -with  the  disturbances  of  iimervation — for  e.\aini)le,  in  connection 
with  the  loss  of  sensibility.  (r<>/z  am]  Eirnfd,  nfwv  comi>letely  destroying  tiie  thoracic 
and  lumbar  portions  of  the  sjjinal  cord  of  dogs,  were  able  through  "great,  care  to  pre- 
serve uninjured  the  skin  of  the  animals  thus  operated  upon ;  they  are,  therefore,  op- 
posed to  the  theory  of  the  existence  of  tropliic  centres  and  nerves. 

Literature. 

{Trojyhoneurotic  TiHsne-ehangcH. ) 

Baldi:  Action  tropbique  du  systeme  nerveux.     Arch.  ilal.  de  biol.,  xii.,  1889. 
ii;>  !  Charcot:  Lecons  sur  les  maladies  du  systi^me  nerveux.     G^uvres  completes,  i.-iii. 
Ill  I  Dejerine  ct  iieloir:  Alter,  nerv.  dans  cert,  cas  de  gangrene.     Arch,  de  phys.,  1881. 
j'^  I  Durdufi:  Exp.  Uuters.  z.  Lehre  v.  d.  trophischen  Nerven.     Cbl.  f.  allij;!    Patli.,  v., 
■  f  1894. 

I  Frankel:  Neurotische  Angiosklerose.     Wien.  klin.  Woch.,  1896. 
it  I  Golz  u.  Ewald:  Hund  mit  verkiuztem  Rlickenmark.     Pflliger's  Arch.,  63  Bd.,  1896. 
fi;  j  Harbitz:  Oiu  de  patologisk-anatom.  Forundriuger  af  neuratrofisk  opriudelse,  Chris- 
'  ;  tiania.  1(1(10. 

Hochenegg:  Ueber  svmnietrische  GangrSn,  T\'ien,  1886. 
™  1  Joseph;  Xeurotischelluutgangran.     Arch.  f.  Derm.,  31  Bd.,  1895. 
Kopp:  Trophoneuroseu  der  Ilaut,  "Wien,  1886. 
Kriege:  Vasomot.  Stiirungen  d.  Haut  bei  traumat.  Neurosen.     Arch.  f.  Phys.,  22  Bd., 

1890. 
Iieloir:  Rech.  clin.  et  anatomo-pathol.  snr  les  affections  cutanees  d'origine  nerveuse, 

Paris,  lss-,>. 
Pitres  et  Vaillard:  Gangrenes  niassives  d'origine  nevrotique.     Arch,   de  phvs.,  v., 

188o. 
V.  Recklinghausen:    Allg.  Pathol,  des  Kreislaufs  und  der  Ernilhrung,  Stuttgart, 
18S3;   ^Multiple  Fibrome  d.  Haut,  Beriin,  1882;  Akromegalie.     Virch.  Arch.,  119 
Bd.,lsyo. 
Rosenbaiim:  Symmetrische  Asphyxie.     Euleuburg's  Jahrb.,  ii.,  1892. 
Schlesinger:  Syringomyelie,  Wien,  1895. 
,   Schwimmer:  Die  neuropathischen  Derniatosen,  Leipzig,  1883. 
Springer:  Dactvlite  liypeitrophiciue  synietri(iue.     Bev.  de  med.,  vii.,  1887. 
Weir  Mitchell:  Des  lesions  des  nerfset  <le  leur  consequences,  1874. 
Ziegler:  Ursachen  d.  pathol.  Gewebsneubildungen.     Internat.  Beitr.  Festschr.  f.  Vir- 
chow,  ii.,  Beriin,  1891. 


IV.  Autointoxications  and  Disturbances  of  Internal  Secretion. 

§23.  Autointoxication  or  self-poisoning  may  tak«'  ])lac('  in  a 
variety  of  ways.  In  tlie  first  place,  ;>o/.so;(o».s  jv/W«c/.s  of  mrlnholism  of 
nornial  character  and  produced  in  normal  amounts  ma  ij  fail  of  proper  r.r- 
eretioii,  and,  beinj,^  canicd  over  into  the  juices  of  the  body,  may  l»c 
retained  in  the  same.  Secondly,  tlie  phytiiolon'ival  prod iid ion  (f  poisonous 
substances  may  be  patholofiicallji  increased.  Thirdly,  it  may  hai)i>en  tiial 
poisonous  products  of  metabolism,  wliich  normally  aie  decomposed  and 
thereby  rendered  hiiiinless,  may,  as  a  residt  of  a  local  or  K<'i><-ial  meta- 
bolic disturbance,  escape  such  destruction.  Finally,  it  may  also  happen 
that,  as  the  result  of  patholo<Tical  changes  or  ces.sat  ion  ol'  tlit- I  unci  ional 


76  THE    GEXERALIZATIOX    OF    DISEASE. 

activif}/  of  certain  orfianH.  poisonous  substances  may  appear  in  the  Mood  and 
also  in  the  urinr.  According  to  the  place  of  origin  poisons  may  be  classed 
as  enterogenous,  arising  in  the  intestine,  and  histogenous,  arising  in 
the  tissues. 

If  injurious  products  arising  from  the  decomposition  of  albumin  are 
retained  or  formed  in  excessive  amounts  in  the  intestin(d  canal,  they  may  give 
rise  to  both  local  changes  and  a  general  intoxication.  For  example, 
through  the  action  of  the  bacteria  present  in  the  intestines,  the  suJ- 
phuretted  hydrogen,  arising  from  the  sulphur  of  albuminous  bodies,  may 
be  formed  in  such  amount  as  to  pass  into  the  blood  and  impart  its  char- 
acteristic odor  to  the  breath,  and  to  be  found  also  in  the  urine.  Further, 
those  toxic  substances  especially  which  arise  from  the  decomposition  of 
albumin  through  the  action  of  the  intestinal  bacteria,  when  taken  up 
into  the  blood  are  able  to  produce  symptoms  of  poisoning,  vomiting, 
headache,  vertigo,  stupor,  acceleration  and  weakening  of  cardiac  acti^•ity, 
etc.  This  action  of  toxins  is  especially  marked  in  those  cases  in  which 
there  is  fpecal  retention  or  when  the  stomach  or  pancreas  x)roduces  little 
or  no  enzyme,  it  being  known  that  the  enzymes  have  a  neutralizing  action 
upon  certain  toxins  (see  §  29).  It  is  also  probable  that  the  tetany  oc- 
curring rarely  in  dilatation  of  the  stomach  may  be  due  to  an  autointoxi- 
cation. 

If  the  function  of  the  kidneys  is  disturbed  to  such  a  degree  that  the  sub- 
stances convertible  into  urea  are  excreted  in  insufficieut  quantity,  symptoms 
of  intoxication  may  manifest  themselves  as  the  result  of  the  retention  of 
these  substances.  These  symptoms  are  characterized  by  a  condition  of 
coma  intermitted  by  convulsions  and  by  disturbances  of  respiration — ^the 
symiitoms  collectively  being  designated  as  uraemia.  According  to  von 
Limbeck,  the  retained  substances  have  a  narcotic  action,  the  first  effects 
<)f  the  narcosis  being  a  dulling  of  sensibility  and  insomnia.  It  has  not 
been  yet  been  determined  whether  the  toxic  effects  are  due  to  a  single 
element  or  to  a  mixture  of  substances.  According  to  the  investigations 
of  Bohne,  it  is  very  probable  that  the  retention  of  chlorides  in  the  organ- 
ism Inlays  the  most  important  part  in  the  production  of  this  condition. 
Besides  the  products  of  normal  metabolism,  those  arising  in  the  course  of 
certain  diseases  (infections)  may  also  have  a  toxic  action. 

Since  many  substances  are  excreted  by  way  of  the  intestines,  it  is 
possible  that  under  certain  conditions  a  disturbed  function  of  the  intestines 
may  render  it  difficult  for  the  organism  to  rid  itself  of  poisons  and  in 
this  way  lead  to  an  autointoxication,  copraemia.  Likewise,  an  excessive 
accumulation  of  carbonic  acid  within  the  blood,  through  some  interference 
with  the  exchange  of  gases  in  the  lungs,  may  cause  symptoms  of  poisoning. 

When  the  excretion  of  h\\&  from  the  liver  is  hindered  or  arrested,  through 
some  pathological  condition  in  the  bile-passages  or  in  the  liver  itself, 
the  elements  of  the  bile  are  taken  up  into  the  blood,  and  the  condition 
known  as  cholaemia  is  produced.  Both  the  biliary  salts  and  bile-pigment 
enter  the  blood,  and  their  presence  in  the  circulation  gives  rise  to  gen- 
eral lassitude,  depression,  mental  exhaustion,  inclination  to  sleep,  slow- 
ing of  the  pulse-rate,  itching  of  the  skin,  and  abnormal  sensations  of 
hearing  and  taste.  The  effects  upon  the  heart,  muscles,  and  central  ner- 
vous system  are  ascribed  to  the  bile-salts.  These  also  possess  a  hsemo- 
lytic  action  upon  the  red  blood-cells.  According  to  Bickel,  ammonia- 
salts,  leucin,  and  phenol  must  also  be  taken  into  consideration  in  the 
explanation  of  the  symptoms. 

If  the  liver  has  undergone  marked  pathological  changes,  not  only  does 


AUTOIXTOXICATKJX.  77 

the  production  of  the  bile  as  well  as  that  of  su^ar  ami  uiva  sullcr  l.iil 
( .ilaiii  substauoes  bioiioht  to  the  liver  from  the  intestines  and  nonnallv 
<lr(onii)osed  by  this  organ  may  i^ass  Ihrouoh  it  uneiianyed.  :\Iany  be- 
lirvo  jhat  at  least  the  severe  symptoms  (conditions  of  mental  exeiteiiient 
(l.liiium,  letharoy,  coma,  and  eerebral  paralvsis)  whieh  oceur  in  de-en- 
.  rations  ot  the  liver  (icterus  o-ravis)  are  to  be  referred  in  i)art  t.Tthe 
])ivsence  of  such  substances  in  the  blood,  and  base  their  belief  uix.n  the 
ta.t  that  under  such  conditions  abnormal  substances  (ammonium  carbo- 
iiaie)  appear  in  the  urine.  In  degenerations  of  tin-  pancreas,  hii-e 
aun.untsol  dextrose,  acetone,  and  aceto-acetic  acid  (^see  §  25)  may  ap- 
]uar  in  the  blood  and  urine.  The  two  last-named  substances  have  a 
toxic  action,  and  many  are  disposed  to  asci-ibe  such  symptoms  to  a  dis- 
tuil)ance  ot  pancreatic  function.  Finally,  after  degeneration  of  the 
thyroid  or  adrenals  (s§  25  and  2G),  pathological  symi)toms  arise  which 
l.nssibly  may  be  explained  in  part  by  the  assumption  that,  as  the  result 
oi  the  degeneration  of  these  organs,  poisonous  products  of  metabolism 
arc  no  longer  destroyed. 

In  the  constitutional  disease  known  as  gout,  local  deposits  of  meta- 
bolic products,  m  the  form  of  urates,  give  rise  to  local  tissue-degenera- 
1  ions  and  inflammations. 

The  condition  of  eclampsia  gravidarum  is  an  autointoxication  re- 
sult ing  from  pregnancy,  and  is  probably  due  to  poisons  originating  in  the 
Id'tal  placenta. 

The  term  autointoxication  is  not  used  with  the  same  significance  by  all  writers, 
many  of  them  giving  to  it  a  broader  meaning  than  the  one  given  above,  imd  even  ap- 
l^lying  the  term  autointoxication  to  certain  intoxications  caused  by  pathogenic  bacteria. 
Ill  justification  of  such  a  view  it  may  be  said  tiiat  the  poisons  in  such  cases  arise  for  the 
-icatcr  part  from  component  elements  of  tlie  body.  At  the  same  time  such  a  widen- 
in::-  of  the  significance  of  the  term  appears  to  me  inexpedient,  in  that  the  cause  of  the 
ilrf. imposition  lies  not  in  the  body  itself,  but  comes  from  without,  so  that  the  intoxica- 
tiun  is  tlie  result  of  a  preceding  infection.  It  seems  to  me,  therefore,  to  be  more  correct 
In  ai^iily  tlie  trrin  autointoxication  only  to  those  forms  of  poisoning  wliich  are  i)roducc(i 
by  ]iroduets  of  n>etaliolism,  either  under  the  influence  of  the  activity  of  the  body-cells 
i>r  through  the  activity  of  bacteria  constantly  present  in  the  intestine.  As  authoriza- 
lion  for  including  the  poisoning  by  products  arising  from  intestinal  decomposition 
among  the  autointoxications,  I  draw  upon  the  fact  that  the  intestinal  bacilli  which 
rausc  this  decomposition  are  constant  inhabitants  of  the  intestine,  and,  according  to  the 
in\istigations  of  Schottelius,  are  indispensable  factors  in  the  proces.ses  of  nutrition  of 
man  and  the  hi srher  vertebrates.  The  enleror/enonfi  (nitointoricnlions,  wliich  are  caused 
li\  ilhvi- intisiiiial  bacteria  and  Avhich  occur  especially  in  childhood  through  retention 
I't  the  intestinal  contents  (ileus)  or  in  acute  digestive  disturbances  (asthma  dyspep- 
tii  am),  arc-  in  their  severe  forms  characterized  chiefly  by  disturl)ance  of  heart-action, 
-niall  and  frequent  pulse,  cyanosis,  coldness  of  the  extremities,  sunken  exi)ression,  an(i 
liiwrring  of  the  body  temperature.  They  may  owe  their  origin  in  ]iiirt  to  retention  of 
Intestinal  contents  in  this  or  that  portion  of  the  intestinal  tract,  and  in  part  to  clianges 
n  the  products  of  decomposition  (formation  of  toxins)  depending  eitiier  upon  tiie  es- 
pecial character  of  the  material  taken  into  the  intestines  (deliciency  of  carboiiydrates, 
partitularly  of  sugar,  favors  the  extension  into  the  small  intestine  of  jtrocesses  of  de- 
imposition  normally  confined  to  the  colon),  or  upon  a  change  in  the  virulence  of  the 
l>a(ieria.  or  upon  a  deficient  production  of  enzymes.  It  is  not.  always  possible 
in  snch  cases  to  decide  whether  other  bacteria,  foreign  to  the  iulesline,  are  not 
ilso  concerned  in  the  production  of  poisons.  The  appearance  of  cystin  in  the  urine  is 
;,,  lie  regarded,  according  to  the  researches  r)f  Bnumaiiii  and  von  Uifnnm/,!.  as  evidence 
'f  i-pccial  processes  of  intestinal  deconi])osition  resulting  in  the  production  of  diamins. 
The  hypothesis  that  puerperal  eclampsia  is  an  autointoxication  dependent  upon 
prfimancy  is  at  the  present  time  .supported  by  the  majority  of  writers.  Clinically 
flic  formation  of  toxic  substances  during  pregnancy  may  be  recognized  by  the  occur- 
rence of  nausea,  vomiting,  emotional  depression,  chorea,  hiemogloJ)inuria,  albuminuria. 
iiiil  finally  by  eclampsia.  The  anatomical  findings  in  women  wlio  have  died  f>f  eclanipsia 
me  multiple  thromboses  in  the  .smaller  vessels  and  capillaries,  and  focal  degenerations, 
'-ually  associated  with  haemorrhages  in  the  liver,  kidneys,  brain,  and  lungs,      bi  the 


/8  THE    GENERALIZATION    OF    DISEASE. 

iungs  there  are  also  often  fomid  syncytial  cells  or  portions  of  the  chorionic  villi.  Th 
fibrin-content  of  the  blood  is  markedly  raised.  Should  the  child  die  (as  takes  place  i: 
about  forty  per  cent  of  cases)  corresponding  changes  may  be  found  in  its  organs. 

It  was  at  first  thought  that  the  place  of  origin  of  the  poison  was  in  the  materna 
organism,  and  the  cause  was  sought  in  alterations  of  proteid  metabolism  in  which  tli 
disturbances  of  function  were  at  one  time  located  in  the  kidneys,  at  another  time  ii 
the  liver  or  in  the  thyroid.  Recently  the  view  has  been  advanced  that  the  intoxica 
tion  is  to  be  referred  to  products  of  the  placenta  (cytotoxins).  \'eit  assumes  a  direc 
intoxication  through  placental  elements  which  takes  place  when  the  placental  toxin  cai 
no  longer  be  rendered  inactive  through  the  formation  of  antitoxin  (syncytiolj-sin 
On  the  other  hand,  Arcoli  believes  that  the  mother  produces  an  excess  of  syncytiolysi 
and  therebj^  poisons  herself.  Weichart  thinks  that  there  are  formed  through  syncyti 
olysis,  that  is,  the  solution  of  the  transported  placental  elements,  albumin  bodie 
(syncytiotoxins)  which  are  poisonous  to  the  mother.  At  the  present  time  it  cannot  b 
decided  which  one  of  these  hypotheses  corresponds  most  fully  to  the  actual  conditions. 

According  to  the  view  of  Bouclinnl,  autointoxications  are  caused  in  particular  b; 
leucomai'ns— that  is,  by  the  earlier  products  of  retrogressive  metamorphosis  of  albumir. 
ous  bodies,  wliich  normally  are  further  decomposed  in  the  process  of  intra-organic  ox 
datiou  until  they  reach  the  form  of  urea  and  are  then  excreted. 

Literature. 

{Autointoxications. ) 

Albu:  Die  Autointoxicationen,  Berlin,   1895   (Lit.);    Jahrb.  v.    Eulenb.,  viii.,   189 

(Lit.);   Harngift.     Virch.  Arch.,  166  Bd.,  1901. 
Ascoli:    Vorlesungen  liber  Uramie,  Jena,   1903. 
Baumann:  Die  aroma tischen  Verbindungen  im  Harn  u.   d.   Darmfaulniss.     Zeit. 

phys.  Chem.,  x.,  1886;   Vork.  v.  Diaminen,  sog.  Ptomainen  im  Harn  bei  Cystinuri( 

ib.,  xiii.,  1889;   Alkaptonurie,  ib.,  xv.,  1891. 
Bickel:   Pathogenese  der  Cholamie,  Wiesbaden,  1900. 
Blum:   Autointoxicationen.     Miinch.  med.  Woch..  1900. 

Bohne:   Bedeutung  d.  Retention  v.  Chloriden.     Fortschr.  d.  Med.,  xv.,  1897. 
Bouchard:    Lemons  sur  les  autointoxications,  Paris,  1887. 
Bubis:   Sperm immi-Poehl   in   chem.   u.   physiol.   Beziehung.     St.   Petersburger  mec 

Woch.,    1894. 
Charrin:    Poisons  de  I'organisme,  Paris,  i.-iii.,  189.3-1897. 
Chatrin  et  Guinard:    Secret,  int.  du  rein  (has  no  internal  secretion).    Arch,  de  med 

exp.,  1900. 
Chittenden:   Autointoxication.     Proc.  of  the  Path.  Soc.  of  Philadelphia,  ii.,  1899. 
Colosanti:  La  fonction  protectrice  du  foie.     Arch.  ital.  de  Biol.,  xxvi.,  1897. 
Dopter:   Paralysies  centrales  de  nat.  autotoxique.     Arch,  de  med.  exp.,  1903. 
Ewald:    Die  Autointoxication.     Berl.  klin.  W^och.,  1900. 
Ewing:  The  Patliological  Anatomy  and  Pathogenesis  of  the  Toxaemia  of  Pregnane^ 

Amer.  Jour,  of  Obstetrics.,  vol.  51,  1905. 
Fermi  u.  Caciani:   Autointoxication.     Cbl.  f.  Bakt.,  xix.,  1896. 
Fleischer:  Beitr.  z.  exp.  Path,  der  Niere.     Verb.  d.  VL    med.    Congr..  Wiesbadei 

1SS7. 
Harz:   Die  Storungen  des  Verdauungsapparates  als  Ursache  und  Folge   anderer  E 

kraiikuiigeii,  Berlin,  1898. 
Honigmann:    Die  Uramie.     Ergebnisse  d.  allg.  Path.,  viii.,  1904  (Lit.). 
Kobert:    Lehrl).  der  Intoxicationen,  Stuttgart,  1893. 
V.  Limbeck:    Zur  Lehre  v.  d.  uramischen  Intoxicationen.     Arch.  f.  exp.  Path.,  3i 

Bd..  1892. 
Martius:    Pathogenese  innerer  Krankheiten.  i.  and  ii.,  Leipzig,  1900. 
Minkowski:   Die  Storungen  d.  Leberfunctionen.     Ergebn.   d.  path.  An.,  ii.   Jahr 

Wicsb..  IS!)7. 
Muller  u.  Brieger:  Autointoxicationen  intestin.  Ursprungs.     Verb.  d.  Congr.  f.  ini 

.Med.,  1.S9S.  ^       " 

Nesbitt:    Res.  on  .Vutointoxication.      Journ.  of  Exp.  Med.,  vi.,  1899. 
Pfeiffer:    Vorkonunen  u.  .\etiologie  der  Tetanic.     Cbl.  f.  allg.  Path.,  vii.,  1896  (Lit.) 
Roger:   Les  autointoxications.     Path.  gen.  publ.  p.  Bouchard,  i.,  1895. 
Buffer  and  Crendiropoulo:   Toxic  Property  of  Bile.     J.  of  Path.,  ix.,  1904. 
Salaskin  u    Zaleski:  Einfl.  d.  Leberextirp.  auf  d.  Stoffwechsel.    Z.  f.  phvs.  Chem., 

Ji.l.,   1900.  y  y  ' 

Schottelius:  Bedeutung  der  Darmbakterien  fur  die  Ernahrung.     Arch.  f.  Hyg., 

Bd.,  1898.  s  JS  - 


DISTiRBAXCE    OF    IXTKKXAL    SKCKKTIONS.  79 

Schwalbe:  Vergiftun?;.     Eulenburs's  cncyklop.  Jalirh..  iv..  is<il. 
tSeidel:    Die  Lehre  von  d.  Eklainpsia  {rravidarum.      1).  mcd.  WOcli,.  I'.iOl  (I. it.). 
Stadelmann:    Der  Ikterus.  Stuttirart,  IS'H. 

Strauss:    The  ToxaMiiia  of  PiTiriiaiicy.     Aiuer.  Jour,  of  Oh.stotrics.  vol.  liii.,  19()(). 
Uschinsky:   Intoxication  ilurcli  Schwefchvasscrstoff.     Zeitschr.   f.   plij-.s.  Choni.,  17 

Bd..   1S92. 
^Weintravid:   Gastrointestinale  Autointoxication.     ErRchn.  d.  allfi   Path.,  iv.,  1807. 
JWernigk:    Ucber  die  bei  uraniischen  Anfiillen  auftret.  Verandorungen.     Inauir.-I)i.s.s., 

|j-ianfren.  1SS7. 
Winkler:    Ziir  Lohre  v.  d.  i:klanipsie.      \ireli.  .Vrcli..  !.">  I  lid.,    IS'ts. 
Wolf:    Tlio  Cheini.strv  of  tlie  To-xa-nua   of    Prcirnancv.     .New    York   .Med.    .lour.,  vol. 
I         Ixxxiii.,  1!)0(). 
iWormer:   Zur  modernen  Lehre  von  der  Eklainp.sio.     Miincii.  nied.  \\ Ocli..  MtOl. 

1  §  24.  If  II  glaiul  produces  an  internal  secretion — that  is,  if  it  gives 
to  the  lymph  or  the  bU)0(l  certain  substances  whicli  are  necessary  foi"  the 
[uonual  performance  o(  the  functions  of  otlici'  oi^ans  m  of  tlie  oiganism 
las  a  Avhole — an  alteration  or  total  failure  of  this  function  w  ill  cause 
more  or  less  important  disturbances  of  nutrition,  as  an  ell  as  of  the  fuuc- 
tioual  activity  of  other  organs  and  of  the  entire  organism.  Such  an  iu- 
[ternal  secretion  is  ascribed  to  tlie  liver,  i)aucreas,  tliyroid,  adrenals, 
thymus,  and  the  sexual  glands,  yet  our  knowledge  of  the  nature  of  tliese 
secretions  is  very  slight  and  hypothetical.  We  are  able  to  infer  the  in- 
fluence exerted  by  these  glands  upon  metabolism  and  the  life  of  the 
organism  only  from  the  disturbances  -which  arise  when  the  glands  in 
question  become  diseased.  Among  the  most  important  of  the  diseases 
belonging  in  tliis  category  are  diabetes  meUitu.s,  tJn/reopriral  eaehexia, 
mi/xocdema,  cretinism,  Addi.son''s  disease,  and  the  functional  and  anatomical 
chanf/es  occurring  in  the  body  after  castration.  In  a  certain  sense  it  is 
proper  to  consider  in  this  connection  asphyxia,  which  arises  from  a  fail- 
tire  of  the  lunf/s  to  perform  properly  their  function,  in  that  through  the 
{functional  activity  of  the  lungs  the  requisite  amount  of  oxygen  is  sup- 
ll^lied  to  the  organism. 

I  Diabetes  mellitus  is  a  disease  which  is  characterized  especially  by 
j:he  presence  of  large  amounts  of  grajje-sugar  in  the  urine  (glycosuria), 
|ieeompanied  by  a  great  increase  in  the  total  amount  of  urine  secreted 
[polyuria),  and  often  also  by  a  jjathological  increase  of  acetone  and  the 
excretion  of  aceto-acetic  acid  and  ,5-oxyl)utyric  acid  in  the  urine.  At 
'he  same  time  grape-sugar  and  these  acids  aic  found  in  the  blood  and 
jDften  lead  to  a  diminution  of  Its  alkalinity.  AVhen  the  acid-content  of 
he  blood  is  high,  headache,  anxiety,  delirium,  fainting,  and  finally  a 
pondition  of  loss  of  consciousness  (coma  diabeticum)  develoi).  and  these 
ponditions  are  probably  to  be  ascribed  to  an  acid-intoxication. 
j  The  entrance  of  sugar  into  the  urine  may  be  cau.sed  by  too  great  an 
ngestion  of  sugar,  so  that  part  passes  into  the  urine  unclianged  (ali- 
nentary  glycosuria).  Glyco.suria  may  also  follow  an  injury  to  certain 
portions  of  the  medulla  oblongata  (])unctnre  of  IJernaid).  or  as  the  residt 
3f  disease- processes  in  the  brain  (degenei-ation,  epilepsy,  mental  aflVc- 
ions,  severe  psychical  disturbances,  tumoi.s,  parasit<'s),  oi-  of  certain 
onus  of  poisoning  (carbon  monoxide,  curare,  mori)hine,  strychnine, 
'imyl  nitrite,  nitrobenzole),  in  which  the  liver  ]irobably  gives  u])  its  gly- 
I'ogen  into  the  blood  moie  rapidly  than  normal,  so  that  a  condition  of 
lyperglycaemia  is  i)roduced. 

Finally,  glycosuria  may  be  due  to  an  inability  on  lli.-  itart  of  the  ki<l- 
leys  to  hold  back  the  small  amounts  of  glucose  found  n(.rmally  in  the 
blood,   a  phenomenon  which  nuiy  be  produced  experimentally  by  tlu^ 


80  THE    GEXEKALIZATIOX    OF    DISEASE. 


I 


administratiou   of   phloridzin   (von   Meriug)    or    of   caffeine    sulphate 
(Jacobj). 

These  alimentary,  nervous,  and  toxic  glycosurias  are,  however,  to  be 
distinguished  from  the  ordinary  form  of  diabetes,  in  that  in  the  latter  the 
cause  of  the  glycosuria  is  to  be  sought,  not  in  an  increased  conveyance 
of  sugar  into  tiie  blood,  or  in  a  pathological  excretion  of  the  sugar  cou- 
tained  in  the  blood,  but  much  rather  in  the  fact  that  the  diabetic  patient 
is  unable  to  decompose  sufficiently  the  carbohydrates,  and  especially 
dextrose,  while  the  sugars  which  turn  polarized  light  to  the  left  (levu- 
lose  and  inulin)  oidinarily  can  be  oxidized  either  wholly  or  at  least  in 
greater  amounts  than  dextrose.  In  most  cases  the  power  to  form  fats 
from  the  carbohydrates  is  also  lessened,  yet  there  are  cases  in  which  this 
function  is  unimpaired  and  the  sugars  are  stored  up  in  the  body  in  the 
form  of  fat  (diabetogenous  obesity). 

According  to  the  investigations  of  von  Mering  and  Minkowski,  which 
have  been  confirmed  by  different  authors,  this  loss  of  ijower  in  the  or- 
ganism to  oxidize  the  sugars  brought  into  the  body  or  formed  normally 
in  the  body  from  albumin,  or  to  store  them  up  as  glycogen  or  fat,  is  to 
be  ascribed  to  an  insufficiency  of  pancreatic  function.  This  conclusion 
is  drawn  chiefly  from  the  fact  that  after  total  extirpation  of  the  pancreas 
in  dogs,  a  diabetes  of  severe  character,  usually  fatal  within  a  few  weeks, 
is  produced,  this  being  characterized,  as  is  diabetes  in  the  human  sub- 
ject, by  polyuria,  polydipsia,  hyperglycaemia,  glycosuria,  diminution  of 
the  glycogen  of  the  tissues,  also  at  times  by  marked  destruction  of 
albumin,  emaciation,  excretion  of  large  amounts  of  acetone,  aceto-acetic 
acid,  ,5-oxybutyric  acid,  and  ammonia,  as  well  as  by  the  occurrence  of  a 
comatose  condition.  In  support  of  the  view  that  there  is  a  definite  re- 
lation between  disturbances  of  pancreatic  function  and  diabetes,  it  has 
been  found  that  in  certain  cases  of  this  disease  in  man  the  pancreas  has 
exhibited  demonstrable  changes,  of  the  nature  of  atrophy  or  degenera- 
tion. It  should,  however,  be  borne  in  mind  that  the  anatomical  investi- 
gation often  fails  to  reveal  a  pathological  condition  of  the  pancreas;  so 
that  we  are  forced  to  content  ourselves  with  the  hypothesis  that  the 
anatomical  changes  underlying  the  functional  disturbance  of  the  pan- 
creas are  not  demonstrable. 

An  exact  ex[)lanation  of  the  causal  relations  existing  between  i)an- 
creatic  disease  and  diabetes  cannot  at  the  present  time  be  given,  yet  from 
the  foregoing  experimental  researches  the  hypothesis  may  be  deduced 
that  the  pancreas  produces  an  internal  secretion  which  either  gives  the 
body  the  power  to  destroy  glucose  or  increases  this  glycolytic  capacity. 
Likewise,  no  explanation  can  at  present  be  given  for  the  increased  de 
struct  ion  of  the  albumins  and  the  accompanying  abundant  production  ot 
/^oxy butyric  acid,  aceto-acetic  acid,  and  acetone.  Since  these  substance> 
are  not  always  found  in  experimental  pancreatic  diabetes,  their  forma 
lion  probably  does  not  stand  in  direct  relation  to  the  excretion  Ox  sugar, 
but  is  to  be  legarded  rather  as  a  complication  of  diabetes  (Minkowski). 
Their  occurrence  in  diabetes,  moreover,  is  not  always  constant,  ami 
Ihey  are  fountl  in  other  diseases  (_ intoxications,  carcinoma,  disturbances 
of  digestion). 

The  occurrence  of  (liubcfis  after  total  extirpation  of  the  pancreas  is  evidence  tha^ 
this  organ  jjossesses  a  special  function  which  is  of  the  greatest  importance  in  tlie  nor 
null  consumption  of  sugar  in  the  organism.  Lepine  is  of  the  opinion  that  there  is  in  the 
blood  a  glycolytic  ferment,  which  is  formed  by  the  pancreas  and  passed  from  this  or 
gan  into  the  blood;  and  that  the  cause  of  the  mellituria  in  diabetic  patients  and  iu  dog: 


DIABETES    MELLITIS.  81 

from  which  tlie  pancreas  lias  been  removed  is  to  lie  sounlit  in  a  (ieeresise  in  tlie  nnionnt, 
if  this  ferment.  According  to  Cohnluim,  Raltel,  llirxch.  Antlniiii,  lUmiit utlml.  iiiui 
iliiers  tlie  pancreas  has  the  power,  in  a  way  not  yet  exphiined,  of  exciting  to  action  the 
glycolytic  ferments  found  in  the  dillerent  organs.  The  addition  of  pancreatic  emulsion 
[CW//'/'<'///0  l^'^  the  expressed  juice  of  muscle  increases  its  glycolytic  capacity.  At  the 
•irescnt  time  it  is  impossible  to  offer  a  satisfactor}'  explanation  of  the  pathogeiK'sis  of 
>an(  ivatic  iliabetes.  According  to  Stoklasa  the  anaOrobic  respiration  of  the  animal 
■ri:aiis  is  an  alcoholic  fermentation  caused  by  enzymes  whidi  may  be  sefiarated  from 
lie  iclis  antl  obtained  in  the  form  of  jiow'der.  They  will  produce  an  alcoholic  fer- 
inentation  as  long  as  they  are  not  subjected  to  the  action  of  hu'tie  acid  and  thereby  in- 
libited.  In  diabetes  such  an  inhibition  of  the  splitting  of  glucose  into  alcohol  and 
j-arbonic  acid  occurs  through  the  formation  of  lactic  acid. 

1  If  only  a  portion  of  the  pancreas  of  a  dog  be  removed,  no  diabetes  occurs,  or  at 
jeast  the  excretion  of  sugar  is  much  less  than  after  total  extirpation  (Minkowski).  If  in 
logs  from  Avliich  the  ]iaucreas  has  been  totally  removed  a  portion  of  pancreas  is  trans- 
ilantfd  subcutaueou.>^ly,  diabetes  docs  not  follow  {Minkoicski,  Iledon),  but  occurs  if  the 
■lansplanted  piece  be  excised. 

According  to  Minkoirski,  there  is  no  direct  communication  between  the  secretory 
■uuctiou  of  the  pancreas  and  that  function  of  the  organ  concerned  in  the  metabolism  of 
ugar. 

Poisoning  with  phloridzin  produces,  according  to  ron  Mering  and  Minkowski,  a 
[narked  glycosuria  in  most  animals  and  in  man,  and  the  same  symptoms  as  those  .seen 
|a  diabetes,  may  be  produced  by  a  continuous  administration  of  the  poison.  Since  in 
ihis  case  the  cause  of  the  pathological  excretion  of  sugar  lies  in  the  kidneys  and  repre- 
ents  a  flushing-out  of  sugar  from  the  organism,  phloridzin  diabetes  cannot  be  identilied 
[i'ith  the  ordinary  form  of  diabetes  found  in  man — that  is,  with  pancreatic  diabetes.  In 
logs  in  which  diabetes  has  been  produced  by  the  extirpation  of  the  pancreas,  phloridzin 
•reduces  an  increase  in  the  amount  of  sugar  excreted  {Minkowski). 

Literature. 

{Diabetes  MeUitns. ) 

irthaud  ct  Butte:  T?ech.  sur  la  pathogenic  du  diabete.     Arch,  de  phys.,  i.,  1888. 

lernard,  Claude:  Lccons  sur  le  diabete,  Paris,  1877,  and  Berlin,  1878. 

llumenthal:    Ueber  das  glykolytische  Ferment.    D.  med.  Woch.,  1903  (Lit.). 

Joccardi:  Alterations  anat.  consec.  a  I'exportation  du  pancreas.    Arcli.  ital.de  Biol., 

\      wi.,  1S91. 

Dominicis  :  Pathogenic  du  diabete.    Arch,  de  med.  exp.,  v.,  1893. 

Abstain:  Die  Zuckeiluiriirulir,  Wiesbaden,  1887. 

'einschmidt:  Euthaltcn  d.  tier.    Zellen  ein  Zucker  zerstoren.  Ferment.    Fortschr.  d. 

i      Med.,   19U3. 

'rerichs:  Ueber  den  Diabetes,  Berlin,  1884. 

iaglio :  Ueber  den  Diabetes  nach  Abtragung  des Pankreas.   Cbl.  f .  allg.  Path. ,  ii. ,  1891. 

■aleotti:  Glykosurie  und  Acetonurie.    Cbl.  f.  allg.  Path.,  iii.,  1892. 

[ansexnann :  Beziehungen  d.  Pankreas  zum  Diabetes.  Zeit.  f.  klin.  iNIed..  20  Bd., 
1 S94. 

Cedon:  Exstirpation  du  pancreas.  Arch,  de  med.  exp.,  iii.,  1891,  v.,  1893;  Patho- 
trenie  du  diabete.  Arch,  de  phys.,  1892;  Greffe  souscutanee du  pancreas.  Arch,  de 
pliys.,  1892. 

:erter  and  Wakeman .  Adrenalin  Glycosuria.  Virch.  Arch.,  1902:  Anier.  .Tmir.  of 
Med.  Sc,  .Ian.,   1903. 

[erzog:  Zur  Histopatliologie  des  Pankreas beim Diabetes  mellitus.    Virch.  Arch.,  1902. 

^ess:  Das  Wesen  des  Diaiietes.    Munch,  med.  Woch.,  1902  (Lit.). 

-akobj:  Nierendiabetes  (lurch  CafTeinsulfosaure.    Arch.  f.  exp.   Path.,  35  Bd.,  1895. 

iaufmann:  Glvcemic  normaie  et  diabete  pancreaticiue.     Arch,  de  iihys.,  vi.,  1895. 

:raus:  Pliloridzin  Diabetes  u.  chem.  Eigenart.     D.  med.  Woch.,  1903.  ^ 

annois  et  Lemoine:  Le  pancreas  dans  le  diabete.     Arch,  de  med.  cxper.,  iii.,  1891. 

epine:  Le  ferment  glycolvtiqueet  la  pathogeniedu  diabCte,  Paris,  1.S91 ;  S.  I'exstirpa- 
tion  du  pancreas.  A.  *de  med.  exper..  iii.,  1891;  Patliogenie  de  la  glycosurie,  ib., 
iv.,  1892;  Le  diabete  et  les  lesions  du  pancreas.  Kev.  de  med.,  xii.,  1892;  Pa- 
thogenic du  diabete,  ib.,  xiv.,  1894. 

orenz:  Unters.  iiber  Acetonurie.     Zeitschr.  f.  klin.  W-(\.,  19  Bd..  1891. 

ustig-:  Function  des  Plexus  co'liacus.     Beitr.  v.  Zieglc'-,  vii..  |S9(). 

:agnus-Levi:  Die  Oxybuttersiiure  u.  d.  Coma  diabet.  Arch.  t.  exp.  Path..  42  Bd., 
1S99. 

r, 


82 


THE    GENERALIZATION    OF    DISEASE. 


V.  Mering-:  Uclu'r  cxperimentellen  Diabetes.  Verhandl.  d.  V.  u.  VI.  Congr.  f.  im 
:\r((l.,  Wicshadcn,  lss(;,_l887;  Zeitschr.  f.  klin.  Med.,  xiv.,  1888,  aud  xvi.,  1889. 

V.  Mering  ii.   Minkowski:  Diabete.s  mellitiis  nacli  Pankreasexstirpation.     Arch. 
('X]U'r.  Pathol.,  26  Bd.,  1890;  Zeitschr.  f.  Biol.,  29  Bd.,  1892. 

Michael:  Diabetes  (Cysticercus  im  IV.  Ventrikel).     Dent.  Arch.  f.  klin.  Med.,  44  Bd 

INS!). 

Minkowski:  Diabetes  nach  Pankreasexstirpation.  Arch.  f.  exp.  Path.,  31  Bd.,  186 
(f.it.).  ^ 

Moritz  u.  Prausnitz:  Phloridzindiabetes.     Zeitschr.  f.  Biol.,  27  Bd. 

V.  Noorden:  Pathologic  des  Stoflfwechsels,  Berlin,  1893  (Lit.). 

Opie:  The  Relations  of  Diabetes  Mellitus  to  Lesions  of  the  Pancreas.  Journ.  of  Exj 
Med.,  vol.  v.,  1901. 

Savierbeck:  Die  Langerhans'schen  Inseln  d.  Pankreas.    Ergebu.  d.  a.  P.,  viii.,  1904. 

Seegen:  La  glycogenic  animale.  Paris,  1890;  Der  Diabetes  mellitus,  Berlin,  1893. 

Stoklasa:   Die  glykolytische  Enzyma  im  tier.  Gewebe.     D.  med.  Woch.,  1904. 

Tiroloix:  Le  diabete  pancr^atique,  Paris,  1892. 

§  25.  Cachexia  thyreopriva  is  a  peculiar  disease  caused  by  defieieri 
orfof<(lli/  ((hsnit  I'll  net  ion  of  tlie  flii/roid,  i-esultiiig  eitlier  from  detective  de 
velopiueiit  or  from  patliological  cliauges  in  the  gland.  To  Kocher,  Avh 
observed  that  it  followed  total  extirjDation  of  the  thyroid,  belongs  th 
honor  of  having  discovered  the  cause  of 
this  disease.  Numerous  clinical  observa- 
tions aud  experimental  researches  which 
followed  this  discovery  have  confirmed  the 
fact  that  the  presence  of  thyroid  tissue  is 
essential  to  the  maintenance  of  the  integ- 
rity of  the  organism,  and  that  the  body, 
especially  during  its  period  of  growth,  le- 
quires  a  thyroid  gland  capable  of  function- 
ating normally.  It  is  probable  that  the 
gland  produces  a  substance  (thyroiodine) 
which  serves  a  useful  purpose  in  the  bodily 
metabolism.  It  is  also  possible  that  this 
gland  neutralizes  or  destroys  poisonous 
substances  circulating  in  the  blood. 

According  to  experimental  and  clinical 
observations,  the  total  extirpation  of  the 
thyroid  gland  produces  in  man  and  in 
animals,  after  a  very  short  time,  severe 
symptoms,  which  are  characterized  espe- 
cially by  muscular  twitchings,  convulsions, 
and  paralysis,  so  that  tlie  condition  has 
been  called  thyreoprival  tetany.  Young 
animals  and  carnivora  ai-e  especially  sus- 
ceptible; dogs  die  for  the  gieater  part  iu 
a  short  time  after  total  thyroidectt)niy. 

If  the  loss  of  tlie  gland  is  at  first  well 
borne,  as  is  the  case  in  man,  there  arise  in 
the  course  of  months  or  years  peculiar  dis- 
turbances of  nuti'ition,  beginning  with 
weakness  and  heaviness  of  the  lin-ibs,  feel- 
ing of  coklness,  often  also  pain  and  ti'an- 
sient  swelling  of  the  limbs,  with  loss  of 
mental  activity,  leading  to  a  cachexia  as- 
sociated witli  ana'mia,  and  cliaracterized 
further  by  i)ale  swellings  of  the  skin,  especially  of  the  face  (Fig.  5),  ai' 
marked  diminution  of  mental  powers,  together  with  a  loss  of  muscul 


aftd  llu  total  extiipatiuii  of  the  tlnu 
gland  in  patient's  tentli  jear;  length 
body  127  cm.    (See  Grundler,  loc.  cit.)  ■ 


:MYX(EDEMA  :    CKK'I  IMSM. 


S.3 


treugtli,  these  symptoms  liiially  termiiiatiiiji"  in  death.  Tlie  iriiK.xal 
f  the  thyroid  jilaiid  in  chihlliottd  eaiisrs  distiii'l»an<'es  of  i^iowili,  the 
lerease  in  length  of  the  hones  I'allinii-  hrhtw  the  normal  or  «M'asin;,^  alto- 
ether  (Fig.  5).  Animals  (i-ahbits  and  goats)  that  liave  had  tlu-ir  thy- 
iiid  glands  riMnoxed  soon  after  hiith  do  not  r<'ach  full  giowtli  and 
e(inire  an  t>xi)ression  of  stni>idity. 

In  Ihyreoprival  tetany  tlic  ImxIv  tcinpnat  nir  is  iiKifascd  ;  in  tlir 
iiehexia  it  is  lowered. 

Disturbances  of  thyioid  function,  as  M«'il  as  total  extirpation,  lead 
)  pathological  conditions  of  the  body.  ]>oth  clinical  observations  and 
xperimental  in^-estigations  tend  to  show  that  tlu'  jx'culiar  disease  (Fig. 
)  known  as  myxoedema  (Ord)  is  due  to  changes  in  tlie  thyi-oid. 
[yxcrdema  is  aconditit»n  in  which  the  external  api)eai'ance  of  tlie  i)a- 
ent  is  suggest i\t' of  thyrt'oi>ri\  al  cachexia,  in  tiiat  the  same  cliaraeter- 
.tic  i)ale  and  elastic  swellings  of  the  skin  of  the  faee  (Fig.  (J),  not  pitting 
n  pressure  with  the  lingers,  are  associated  uith  similar  i)ah'  and  di-y 
■veilings  in  other  parts  of  the  body.  Further,  there  is  a  loss  of  intel- 
'Ctual  power,  which  finds  expression  in  an  increasing  difhculty  in  think- 
ig  and  acting,  dulness  of  the  tactile  sense,  retardation  of  muscular 
•tion,  and  a  monotonous  nasal  voice.  Finally,  a  marked  general 
eakuess  and  often  also  symptoms  of  actual  mental  derangement  occur, 


Fir,.  C— Myxoedema  (case  observed 
by  Meltzrr).  Age  of  patient,  ibirty- 
seven  years. 


Fli;.  7.  My.\"riliMna.  TIk-  Mirtii-  imlivld- 
ual  (Fltr.  «5)  afliT  thn-f  nioiuhs  of  tn-aliiifnt 
wilb  pulverlzeU  sheep's  thyroid. 


id  death  follows  a  gradually  increasing  cachexia  associate 
lis  of  anicmia  and  coma.. 

Indging  from  the  clinical  and  anatomical  cliaiacteiist 
,  the  patients,  cretinism  (Fig.  S)— iliat  is,  t  lie  alteral  ion.> 
tire  and  functions  of  the  body  whicli  eliaraclerize  this  d 
indent  upon  distuibances  of  tiiyroid  function.  In  snppoi 
ithe  fact  that  in  ci-etins  theie  is  always  i>res<Mit  some  deg« 
xjtioD  of  the  thyroid,  the  organ  beingeithei-enlarged  ('goitre 
i'  structure  (endemic  cretinism),  or  either  imperfectly 
i^iolly  lacking  (.sporadic  cretinism  j.      l'uitli<T,  the  general  ; 


1  with  symp- 


pi( 


s  in  th 

•   St  11 

c- 

is«'ase- 

—is  ( 

e- 

•t  of  tl 

is  \'u 

'W 

•neral 

\  e  c< 

n- 

)  and  t 

han- 

•d 

devel. 

.pe.l 

or 

ippeai 

aiice 

of 

84 


THE    GEXERALIZATIOX    OF    DISEASE. 


cretius  (Fig.  8)  is  similar  to  that  of  those  individuals  who  as  a  result  of 
thyroidectomy  in  eai-ly  childhood  (Fig.  5)  have  become  stunted  in  de- 
velopment. The  longitudinal  growth  of  the  long  bones  is  more  or  less 
below  tliat  of  the  normal,  while  the  soft  parts  are  relatively  well  devel- 
oped. The  individnal  portions  of  the  body  are  unequally  developed, 
the  head  is  relatively  large,  the  abdomen  and  neck  are  thick,  the  bridge 
of  the  nose  is  depressed,  while  the  nose  itself  is  broad  and  stumpy ;  the 
skin  is  pale,  flabby,  Avrinkled,  and  puffed,  as  if  oedematously  swollen, 
particuhirly  over  the  face.  The  mental  faculties  are  always  feeble, 
sometimes  markedly  so.  The  power  of  speech  and  of  understanding 
woids  may  be  entirely  absent,  and  only  the  less-marked  cases  of  cretin- 
ism are  capable  of  performing  work  of  any  kind.  The  cause  of  endcinic 
cretinism  is  unknown. 


The  great  importance  of  the  thyroid  gland  for  ,the  general  nutrition  of  tlie  organ- 
ism, the  cerebral  functions,  and  the  development  of  the  bones  has  been  placed  beyond 
all  doubt  by  numerous  clinical  observations  and  ex-  ^ 

perimental  investigations.     As  to  the  exact  mode  of  ~~^^ 

action  of  the  thyroid,  there  are,  however,  different 
opinions.  If  an'animal,  after  thyroidectomy,  is  fed 
with  tlie  thyroid  of  some  other  animal — for  instance, 
that  of  the  sheep — the  injurious  effects  usually  ob- 
served after  removal  of  the  thyroid  do  not  appear 
and  will  occur  only  when  the  feeding  is  stopped.  In 
man  the  administration  of  fresh  thyroid  tissue  or  of 
thyroid  extracts  exerts  a  healing  influence  on  the 
thyreoprival  cachexia  and  myxoedema  (Fig.  7);  and 
reports  have  been  published  of  favorable  results  of 
the  same  treatment  in  children  suffering  from  cretin- 
like disturbances  of  development. 

Goitres  (enlarged  and  hypertrophic  thyroids  with 
nodules  of  new-formed  thyroid  tissue)  which  have 
not  yet  undergone  secondary  degenerations  often 
diminish  in  size  after  the  co'ntiuued  use  of  thyroid 
tissue  for  sevei-al  weeks,  often  with  a  marked  retro- 
gression of  the  follicles  (von.  Bninf(),  but  after  the 
cessation  of  the  treatment  soon  begin  to  grow  again. 

According  to  Jmuz,  the  extirpation  of  the  thyroid 
in  hens  causes  a  diminution  in  size  of  the  eggs; 
feeding  with  thyroid  causes  them  to  increase  in  size. 

According  to  tiie  investigations  of  Baumann,  the 
thyroid  coiistantly  coiitaiiis  an  iodine  substance, 
thyroiodine  or  iodothyrin,  which  is  present  in  the 
greatest  (luaiitity  in  old  individuals,  and  in  the 
smallest  (juantit}'  in  very  young  children.  Iodo- 
thyrin for  the  chief  part  is  usually  comlnned  in  the 
thyroid  with  an  albumin  and  a  globulin  i)ody,  but  it 
may  appear  in  a  free  form.     Tlie  normal  thyroid  is 

able  to  store  up  th(!  extremely  small  amounts  of  iodine  brought  into  the  body  i 
vegetable  foods  or  in  the  drinking-water,  and  to  convert  it  into  the  combination  mci 
tioned  above.  The  internal  administration  of  preparations  of  iodine  or  the  treatment  ( 
wounds  with  such  leads  to  a  greater  accunmlation  of  iodine  in  the  thyroid. 

According  to  Baumann,  iodothj'rin  is  the  active  element  of  the  gland.  Its  emjilo; 
ment  iu  the  treatment  of  goitres,  m}^\a?dema,  and  strumiprival  cachexia,  etc.,  has  tl 
same  effect  as  the  feeding  with  fresh  thyroid  tissue.  It  would  appear  that  the  oi  ua 
ism  requires  iodine  for  its  proper  maintenance,  and  that  the  thj^'oid  supplies  it  with  tl 
necessjiry  iodine-combination.  In  regions  where  goitres  are  not  commonly  fotu 
(North  Germany),  the  thyroid  glands  are,  on  the  average,  much  smaller  (from  oO- 
gm.)  and  contain  more  iodine  (on  the  average  about  Z^  mgm.  instead  of  3  mgm.)  than 
regions  where  goitres  are  niimerous  (Switzerland,  South" Germany).  Whetlier  tiic  la 
of  sullieient  io<line  in  the  food  and  driidiing-water  is  the  cause' of  the  hypertrophi 
condition  of  the  thyroid  in  goitre,  or  Avhether  some  injurious  agent,  perhaps  soi 
lower  organism,  interferes  with  the  specific  function  of  the  gland,  cannot  be  said  ' 
the  present  time.     Among  the   domestic  animals  having  an  especially  large  amou 


FiG.  8.— Female  cretin,  twenty.on 
years  old ;  body-lengtb  84  cm.;  lengt 
of  arm  30cm.;  circumference  of  skul 
53  cm.    (After  Virchow.) 


^fyxcb^dema:  CRETixTs:\r:  acromegaly.  Sa 

iodine  ill  tlie  tliyroid  are  the  sheep,  the  cow.  and  the  calf,  while  in  hogs  the  iodine- 
atent  of  the  gland  is  small. 

Blum  regards  the  thyroid  as  an  organ  whose  function  it  is  to  destroy  cntcrotoxins 
sing  from  the  tlecomiiosition  of  albumin  in  the  intestine. 

Anatomical  investigations  have  failed  to  throw  any  definite  light  upon  the  ciues- 
)n  of  the  internal  secretion  of  the  tliyroid.  It  has  been  proved  that  the  colloid 
lOduceil  by  the  thyroid  cells  passes  into  the  lymi>ii-v(>ssels.  It  is  i)rol)al)le  that 
lotliyrin  is  contained  in  this  colK)id  substance.  During  intra-uterine  life  the  thyroid 
pears  to  be  destitute  of  its  function,  which  in  later  life  is  .so  important. 

It  is  also  possil)le  that  Ba.sedow's  di.sease  (Craves'  di.siM.so,  exophthalmic  goitre), 
lich  is  characterized  by  a  pulsating  goitre,  exophthalmos,  rapid  lieart,  tremor  and 
eat  excitability  on  the  i)art  of  the  patient,  is  dependent  upon  a  ilisea.se  of  the  thyroid 
'namely,  a  hypersecretion  {hyperthyreosis).  In  support  of  this  theory  lies  the  fact 
at  the  glands  of  such  patients  are  rich  in  functionating  gland-tissue,  but  no  positive 
nclusions  concerning  this  point  can  be  drawn  at  the  present  time.  According  to 
'.ebe  the  experimental  feeding  of  thyroid  glands  produces  syini)toms  and  metabolic 
anges  similar  to  those  of  Basedow's  disease.  Removal  of  a  considerable  portion  of 
e  gland  will  in  many  cases  effect  a  cure;  and  the  recurrence  of  the  di.sease  after 
eration  is  in  most  cases  accompanied  by  a  recurrence  of  the  tumor.  Oswald  has 
own  that  the  colloid  of  the  glands  from  cases  of  exophthalmic  goitre  is,  in  the  ma- 
rity  of  cases,  deficient  in  iodine.  He  believes  that  the  symptoms  are  due  to  an 
'erflooding  of  the  l)ody  by  an  excess  of  a  less  potent  secretion.  Bcehe.  Royers.  and 
thers  have  attempteil  to  treat  cases  of  exophthalmic  goitre  with  a  specific  serum, 
it  it  is  j^et  too  early  to  judge  of  the  value  of  such  treatment.  luring  has  stutlied  the 
stological  changes  in  the  glands  of  forty  cases  of  exoi)]ithalmic  goitre,  and  believes, 
common  with  other  writers,  that  the  histological  fintlings  are  to  a  certain  extent 
ecific.  An  extensive  cellular  hyperplasia  with  large  areas  of  imperfectly  formed 
veoli  interspersed  with  giant  cells  ami  resulting  in  nearly  complete  loss  of  colloid 
)pe.irs  not  to  occur  except  in  connection  with  the  nervous  .symptoms  of  Graves'  dis- 
-c.  .">ome  writers  regard  the  thymus  and  parathyroids  as  as.sociated  in  some  way 
niliir  with  the  pathogenesis  of  exophthalmic  goitre,  but  no  definite  proof  of  this  is 
liaiiil.  The  removal  of  the  parathyroids  in  young  carnivora  is  followed  in  a  few 
ly-  hy  symptoms  more  or  less  like  those  of  Basedow's  disease.  Thyreoprival  tetany 
1-  also  been  ascribed  to  the  disease  or  removal  of  the  parathyroids.  Halnied  has 
ported  ca.ses  of  hypoparathyreosis  following  removal  of  the  human  parathyroids, 
le  symptoms  Ijeing  restlessness,  insomnia,  attacks  of  flushing,  and  numbness.  The 
eding  of  fresh  parathyroids  caused  some  improvement.  Transplantation  of  the 
lirathyroids  into  the  thyroid  and  spleen  has  been  successfully  carried  out  experi- 
lentally. 

According  to  the  investigations  of  Royoivitsch,  Stieda,  and  Ilofmeister  the  ex- 
Irpation  of  the  thyroid  in  rabbits  leads  to  a  hypertrophy  and  altered  structure  of  the 
apophysis.  It  would  appear  that  the  role  of  the  latter  organ  in  the  animal  economy 
in  .some  way  correlated  with  that  of  the  thyroid.  Tumors  of  the  hypophysis  have 
;en  repeatedly  observed  in  giantism  and  acromegaly. 

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86  THE    GEXERALIZATIOX    OF    DISEASE. 

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1904. 


ADDISOX'S    DISKASE.  87 

i>  26.  Addison's  Disease  is  51  peculiar  affection,  usually  fatal  after  a 
course  of  about  two  years  on  the  averaj;e,  and  is  M'ly  i)i<)l)al>ly  to  be 
regarded  as  the  result  of  n  functional  diHtiirhancr  of  the  t^upiHtenah.  It  is 
characterized  chietly  by  the  appearauce  of  a  light-yellow-browu  to  dark- 
browu,  dilfuse,  and  si)otted  pii;in«Mitatiou  <»f  the  skin  {nwloHma  supra- 
renale), which  shows  itself  first  in  the  i)ortions  of  the  skin  noinially 
exposed,  later  iu  other  parts  of  the  body-surface  and  iu  the  mucous 
nuMubrane  of  the  mouth.  Even  at  the  beiiiiuiini;'  of  tiie  disease,  or  even 
before  the  pigmentation  of  the  skin,  thei-e  occur  loss  of  appetite,  nausea, 
pain  in  the  epigastrium,  diarrhcea,  constipation,  ancl  vomiting — all 
symptoms  of  a  disturbed  intestinal  and  gastric  function  ;  later,  muscular 
weakness;  and  tinally,  nervous  symi)toms,  asthenia,  fatigue  on  slight 
exertion,  headache,  vertigo,  fainting,  eidleptiforni  attacks,  and  coma. 
Occasionally  a  recognizable  increase  of  the  pigment  of  the  skin  does  not 
occur,  and  the  disease  is  characterized  only  bj'  the  gastro-intestiual 
symptoms,  i)rogressive  weakness,  and  antemia. 

In  about  eighty-eight  per  cent  of  all  typical  cases  of  Addison's  dis- 
ease the  suprareuals  are  found  to  be  diseased,  iu  the  nuijority  of  cases 
being  changed  into  a  caseous  or  fibro-caseous  mass.  3l6re  rarely  there 
are  found  tumors  iu  the  adrenals  or  simple  atrophy,  agenesia,  or  hypo- 
plasia. There  can  scarcely  remain  any  doubt  that  the  disease  of  tlie 
suprareuals  bears  a  causal  relation  to  the  symptoms  described  above ; 
it  niay,  therefore,  be  designated  as  a  suprarenal  cachexia.  In  what  way 
the  loss  or  change  of  the  function  of  the  supraienal  bodies  acts  injuii- 
ously  upon  the  organism  cannot  at  present  be  stated.  It  is  not  impi'ob- 
able'  that  the  supi-arenal  bodies,  like  the  thyroid,  produce  a  substance 
which  is  necessary  for  the  preservation  of  the  organism ;  or  possibly 
poisonous  substances  are  destroyed  by  them. 

A  normal  functional  atltivity  of  the  adrenals  is  necessary  to  the  integrity 
of  the  organism.  This  is  based  not  only  upon  clinical  observations  and  anatomical  in- 
vestigations in  man,  but  also  upon  animal  experiments.  For  example,  the  extirpation 
of  the  adrenals  in  dogs,  rabbits,  cats,  and  guinea-pigs  gives  rise  to  a  lowering  of  blood- 
pressure,  muscular  weakness,  and  nervous  symptoms,  paralysis,  coma,  and,  if  life  be 
sufficiently  prolonged,  a  loss  of  strength.  According  to  the  observations  of  different 
writers  the  adrenals  appear  to  have  an  influence  upon  the  growth  of  the  body.  In 
defective  development  of  the  adrenals  or  in  degeneration  of  these  organs  occurring  in 
early  life  an  abnormal  smallness  of  the  body  has  been  observed;  in  tumor  formations 
of  the  adrenals  leading  po.ssibly  to  an  increased  functional  activity  giantism  has  been 
noted  (Lm.ser).  The  administration  of  adrenal  extract  causes  in  animals  an  increase 
of  blood-pressure,  slowing  of  the  pulse-rate,  increase  in  the  strength  of  muscle-contrac- 
tions after  nerve-stimulation,  and  a  decrease  in  respiratorj^  movements.  The  cau.-^e  of 
the  increase  of  blood-pressure  is  regarded  by  some  as  the  effect  of  the  extract  upon  the 
vasomotor  centre  {Scymonowicz),  by  others  as  a  direct  action  upon  the  heart  and 
the  arterial  walls  {Schdfer).  The  contraction  of  the  small  vessels  has  been  definitely 
proved. 

The  active  principle  of  the  adrenals  obtained  by  different  methods  has  been  put 
upon  the  market  in  two  different  preparations,  adrenalin  anrl  suprarenin.  When 
injected  into  the  ti.ssue  or  applied  to  the  nuicous  membranes  in  strong  solution,  /,, 
pro  mille,  they  produce  ana>mia  through  tlie  contraction  of  the  vessels  and  can  l)e  u.secl 
with  good  success  in  connection  with  local  aiia-sthetics.  In  toxic  doses  adrenalin 
produces  dyspnoea,  diminished  .sensil)ility,  lowered  reflexes,  impairment  of  voluntary 
movements,  and  finally  paralysis.  Diabetes  may  also  appear  after  the  injection  of 
adrenal  extract.  According  to  Loeper  and  Crouzon,  a  temporary  reduction  in  the 
number  of  red  blood-cells  takes  place. 

Since  anatomical  changes  in  the  adrenals  have  not  been  found  in  everj'  case  of 
Addi,son's  di.sease,  many  attempts  have  been  made  to  refer  the  disea.se  to  other  local 
changes,  particularly  to  pathological  conditions  of  the  sympathetic  and  the  .sympathetic 
ganglia.  But  the  anatomical  findings  offered  to  support  this  view  are  not  sufficient 
for  such  an  interpretation.     That  in  a  small  number  of  cases  the  adrenals  appear  to 


88  THE    GENERALIZATION    OF    DISEASE. 

be  unchanged  cannot,  even  if  all  the  cases  of  this  kind  were  diagnosed  properly  (which 
was  probably  not  always  the  case),  be  taken  as  an  argument  against  the  patho- 
genic significance  of  adrenal  degeneration,  since  an  apparently  normal  adrenal  may 
functionate  abnormally. 

According  to  Ciaccio,  Wiesel,  and  others,  the  active  substance  of  the  adrenals  that 
contracts  the  blood-vessels  is  produced  by  the  cells  of  the  medullary  portion  of  the 
adrenal  (the  cortical  portion  is  regarded  as  an  organ  whose  function  it  is  to  neutralize 
or  destroy  poisons).  Chromaffinic  cells  occur  also  in  the  tissues  of  the  sympatlietic 
nervous  system,  and  it  has  been  claimed  that  in  Addison's  disease  the  destruction  of  the 
chromaffinic  cells  plays  the  most  important  role.  On  the  other  hand,  other  writers 
(Karak-dficheff)  are  of  the  opinion  that  the  disease  or  loss  of  the  cortical  substance  of 
the  adrenal  is  of  importance  in  the  pathogenesis  of  Addison's  disease.  Cases  of  de- 
struction of  the  medullary  portion  through  haemorrhage  with  subsequent  calcification 
of  the  necrotic  mass,  without  any  symptoms  of  Addison's  disease,  may  be  regarded  as 
proofs  favoring  this  theory. 

§  27.  As  a  pathological  condition  due  to  the  h)ss  of  a  specific  glandu- 
hir  function  should  be  classed  also  those  abnormal  symptoms  in  the  struct- 
ure and  functions  of  the  body  resulting  from  castration — that  is,  the 
removal  from  the  body  of  the  sexual  glands.  If  the  ovaries  are  removed 
from  a  woman  after  the  age  of  puberty,  menstruatiou  usually  ceases  at 
once,  but  rarely  only  after  some  time.  Sexual  desire  and  the  erethism 
accompanying  the  sexual  act  are  usually  diminished  in  intensity,  but  may 
also  be  unchanged.  The  remaining  portions  of  the  g-enital  apparatus 
undergo  atrophy ;  this  is  especially  marked  in  the  case  of  the  uterus. 
Certain  nervous  manifestations  may  follow,  the  most  common  of  which 
are  excitement,  with  reddening  and  heat  of  the  skin,  especially  of  the 
face,  often  associated  with  attacks  of  sweating;  these  symptoms  being  of 
most  frecpient  occurrence  in  the  period  immediately  following  the  cas- 
tration. The  disposition  remains  unchanged  or  may  become  more  cheer- 
ful, especially  in  those  cases  in  which  the  woman  is  by  the  castration  re- 
lieved of  severe  pain.  At  times  depression  or  melancholia  may  follow. 
If  the  ovaries  are  removed  or  destroyed  during  childhood,  the  secondary 
sexual  characters  aie  not  clearly  defined ;  tlie  muscles  are  more  strongly 
developed,  the  development  of  tlie  pelvis  is  changed,  and  the  breasts  do 
not  increase  in  size. 

Castration  in  an  adult  male  produces  no  marked  change  in  the  build 
of  the  body.  On  the  other  hand,  if  boys  are  castrated,  the  build  of  the 
body  loses  in  masculine  character.  There  occurs  an  increased  deposit  of 
fat,  particularly  on  the  abdomen,  while  the  musculature  is  only  feebly 
developed.  The  external  genitals  remain  small,  the  prostate  is  diminished 
in  size,  and  there  is  no  growth  of  beard  or  pubic  hair.  The  larynx  re- 
mains small,  and  the  voice  is  child-like.  The  mental  powers  are  lacking 
in  energy  and  strength. 

In  castrated  stags,  the  antlers  are  not  developed;  in  cocks  the  combs,  wattles,  and 
ear-lobes  do  not  reach  normal  development,  while  the  feathers  are  developed  to  a 
gre.iter  extent  (Selheim).  In  oxen,  the  horns  and  the  nipples  develop  to  a  greater 
extent  than  in  the  biiU. 

According  to  White,  Kirby,  Kummel,  Bruns,  and  others,  castration  in  fully  devel- 
oped animals  causes  a  decrease  in  the  size  of  the  prostate;  and  it  is  said  that,  in  old  men 
suffering  from  prostatic  enlargement,  castration  may  lead  to  a  diminution  in  size  of  the 
enlarged  prostate.  Others  {Czerny,  Socin)  express  a  less  favorable  opinion  as  to  the 
results  of  castration  in  such  cases. 

In  what  manner  the  extirpation  of  the  sexual  glands  affects  the  entire  body  has  not 
been  determined  with  certainty.  By  many  authors  it  is  assumed  that,  as  a  result  of 
castration,  the  trophic  influence  exerted  upon  the  tissues  by  the  sexual  glands,  through 
the  nervous  system,  is  withdrawn.  The  cessation  of  the  menses  may  mdeed  be  re- 
garded as  due  to  the  withdrawal  of  nervous  stimuli,  and  the  atrophy  of  the  uterus  may 


castration:  lvimpiiatic  coxstitutiox.  so 

perhaps  be  depemlent  upon  the  same  cause;  but  in  general  it  is  more  likely  that  cer- 
tain chemical  substances  (oophorin  and  sijcrmin),  whicli  exert  a  certain  influence  on 
the  functions,  growth,  and  development  of  the  hocly,  are  formed  in  the  sexual  glands. 

Accoriling  to  the  investigations  of  Loewy  and  Richter,  after  castration  of  female 
dogs  there  occurs  a  lowering  of  the  oxidation-power  of  the  cells  of  the  body  and  a  de- 
crease in  the  amount  of  oxygen  used  by  about  twenty  |)cr  cent.  According  to  Brciur 
and  von  Scillcr,  the  total  mass  of  ha^moglol)in  and  red  blood-cells  is  diminished.  The 
administration  of  dried  ovarian  substance  or  of  oophorin  from  the  ovaries  of  the  cow 
or  hog  to  the  animal  operated  upon  causes  an  increase  in  the  amount  of  oxygen  con- 
sumed even  greater  than  the  average  observed  before  the  castration.  Preparations 
of  testicles  showetl  no  such  influence.  In  male  dogs  the  same  conditions  prevailed; 
spermin  caused  only  slight  increase  in  the  gaseous  interchange,  oophorin  gave  a  marked 
increase  (as  much  as  forty-four  per  cent). 

Zoth  and  Prcgcl,  who  have  carried  out  experiments  with  reference  to  the  'effects  of 
glycerin  extracts  of  the  testicles  of  animals,  report  that  injections  of  this  extract 
increase  very  markedly  the  power  of  muscular  contraction. 

According  to  the  investigations  of  Bum  and  L.  Fraenkcl  the  corpus  luteum  appears 
to  possess  an  internal  function.  On  the  one  hand,  it  is  thought  to  govern  the  metabolism 
of  the  uterus  and  to  make  possible  the  insertion  of  the  impregnated  ovum  in  the  uterus, 
and,  on  the  other  hand,  to  excite  menstruation. 

The  thymus  has  also  been  credited  with  the  function  of  an  internal 
.secretion,  and  the  condition  oi  lymphatic  constitution  {constitutiolymphatica) 
has  been  ascribed  to  disturbances  or  loss  of  this  function. 


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Addison:   On  the  Constitutional  and  Local  Effects  of  Disease  of  the  Suprarenal  Cap- 
sules, London,  1855. 
Alezais  et  Arnaud:   Etudes  sur  la  tuberculose  des  capsules  surrenales  et  ses  rapports 

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Alexander:   Die  Xebennieren  u.  ihre  Bezieh.  z.  Nervensystem.     Beitr.  v.  Ziegler,  xi., 

1891. 
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Paris,    IX9(J. 
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Chvostek:    Storungen  d.  Xebennierenfunction.     Ergebnisse,  iii.,  1897. 
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Bd.,  190U. 
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Bd.,  1899. 
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1894. 
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90  THE    fJENERALIZATIO^^    OF    DISEASE. 

Oliver:  On  the  Therap.  Employ,  of  the  Suprarenal  Glands.     Brit.  Mecl.  Journ.,  ii., 

189o. 
Philips:  Addison's  Disease  with  Simple  Atrophy  of  the  Adrenals.    Jo  ir.  of  Exp.  Med. 

1899. 
Rolleston:  The  Suprarenal  Bodies.     Brit.  Med.  Journ.,  1895. 
Schafer:    I'eber  interne  Secretion.     Wien.  med.  Bl.,  1895. 
Scymonowicz:   Function  der  Nebennieren.     Pfluger's  Arch.,  64  Bd.,  1896. 
Tizzoni:  Ueber  die  Wirkungen  der  Exstirpation  der  Nebennieren.     Beitr.  v.  Ziegler, 

vi.,  1SS9. 
de  Vecchi:   Exper.  Tuberkulose  der  Nebennieren.     Cbl.  f.  a.  P.,  xxii. 
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Zander:   Functionelle  u.  genet.  Bezieh.  d.  Nebenn.  zum  Gehirn.     Beitr.  v.  Ziegler, 

vii.,  1890. 

(Eesidts  of  Castration;  Internal  Secretion  of  Sexual  Glands;  Spermin  ana 
Organ-extract  Therapy.) 

Alterthum:   Folgezust.  nach  Castration.     Beitr.  v.  Hegar,  ii.,  1899. 

Breuer  11    von  Seiller:  Einfl.  d.  Kastration  auf  d.   Blutbefund.     A.    f.   exp.   Path. 

50  B(].,  1903. 
Brown-Sequard:   Exper.  dem.  la  puissance  dynamogenique  chez  I'homme  d'un  liquid 

extrait  de  testicules  d'animaux.     Arch.  d.  phys.,  1889,  1890,  and  1891. 
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geb.  d.  Med.  u.  Chir.,  i.,  1896  (Lit.). 
Bubis:   Sperminum-Poehl.     St.  Petersburger  med.  Wochenschr.,  1894. 
Buschan:   Brown-Sequard'sche  Methode.     Eulenburg's  encyklop.    Jahrb.,  iv.,  1894 

Berlin,  1895. — Organsafttherapie,  Eulenburg's  Realencyklop.,  xviii.,  1898. 
Curatvito  ct  Tarulli:   Infl.  de  I'ablation  des  ovaires  sur   le   metabolisme   organique" 

Arcli.  ital.  de  Biol.,  xxiii.,  1895. 
Czerny:   Kastration  bei  Prostatahypertrophie.     Deut.  med.  Woch.,  1896. 
Fiirbringer:   Behandl.  v.  Erkrankungen  m.  Gewebsfliissigkeiten.     Deut.  med.  Wcch. 

1S94. 
Gottschalk:   Kastrationsatrophie  der  Gebarmutter.     Arch.  f.  Gyn.,  53  Bd.,  1897. 
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hang  d.  Geschlcchtskrankheiteu  mit  nervosen  Leiden  u.  die  Kastration  bei  Ner 

vosen,  1885;    Operative  Gyniikologie,  Wiesbaden,  1897.  '■ 

Kiimmel :   Operative  Heilung  der  Prostatahypertrophie.   Berlin.  Klinik,  86, 1895  (Lit."' 
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1896  (Lit.). 
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xxix.,  1898  (Lit  ). 
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Luthje:    I'eber  die  Kastration  und  ihre  Folgen.    A.  f.  exp.  Path.,  48  Bd..  1902. 
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Mdbius:    Die  Wirkungen  der  Kastration.     Halle,  1903. 

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Sellheim:   Secuiuliire  Gesclilechtscharaktere.     Beitr.  v.  Hegar,  i.,  1898. 
Socin:    Kastration  u.  Prostatahypertrophie.     Corr.  f.  Schweizer  Aerzte,  1896. 
Zoth  u.  Pregl:  Wirkung  orchitischen  Extractes.     Pfluger's  Arch.,  62  Bd.,  1895, 


V.   Fever  and  Its  Significance. 

i^  2S.   When  a  local  organic  disease  takes  on  the  character  of  a  get 
eral  disease,  or  wiien  a  disease  at  its  very  inception  manifests  snch , 
character,   there  is  seen  very  frecjnently    a    symptom-complex  which 
designated  as  fever.     Particularly  in  the  case  of  those  infectious  diseas! 
associated  with  symptoms  of  intoxication  does  the  appearance  of  fev' 
diiring  their  course  play  an  impoitant  role.     The  characteristic  sign 
fever  is  -aw  increase  of  bodily  temperature ;  but  accompanying  this  the 
are  other  symptoms,  especially  an  increase  of  the  pulse- rate,  disturbances 
the  distribution  of  the  blood,  changes  in  the  gaseous  interchange  within  t 
lungs,  and  also  changes  in  the  urinary  secretion.     There  is  usually  also 


FEVER. 


91 


sub.iective  feeling:  of  illness,  but  this  is  not  a  necessary  part  of  llie  symp- 

I  toiiuitology  of  fever,  but  an  especial  effect  of  an  infection  associated  with 

symptoms  of  poisoning-,  the  infection  occurring-  at  the  same  time  -with  the 

feverish  increase  of  temperature,  or  before  it,  or  even  after  it. 

i         Observation  of  the  normal  body  has  taught  us  that,  in  spite  of  changes 

of  tenii)erature  externally  and  also  of  chaiigcs  in  other  extrinsic,  coiidi- 

I   tions,  tile  body-temi)eratnre  is  luaintained  at  an  a\erage  lu^iglit  of  .■)7.L*- 

'   37.4°  C.  (98.9(i-99.o2^  F.).     The  absolute  variation  between  morning  and 

I   evening-  is  1-1.5°  C.  (1.8-2.7°  F.),  the  nuiximuni  occurring  at  evening. 

Tlie  elevation  of  temperatui-e  of  the  body  above  that  of  its  surround- 
j   ings  is  due  to  the  fact  that  through  chemical  changes  occurring  in  the  or- 
ganism, particularly  in  the  muscles  and  glands,  heat  is  pi'oduced,  and  to 
'  such  an  extent  that  the  temperature  of  the  body  may  be  raised  one  degree 


!::;:!i:::::;:::s!i:::::;:H:nni:::::!:::H»:;:::r:ni|:^ 

:»:: :::::::::: iiisli:!:::::::;!:::::;::::!::;:; 

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■ ■ ;::; :::::::::::::::::::::  Si:: 

::::;;:::;::::::::::::;::::::::::::::: 

j::::  iLiFfiitMilt;::;:::!::;:::!!:::::::::;: 

I  lnjl!llllilillll!lll;|j;  Hijljllijiliijilp^ 


isssssissg;;;;::;:::::::::::::;;:::::;;;:;:;;: 
ii;;2ii;!ia!;i5llli;a!ii;;;;i;;;Hi;!S;;;iii 


Pig.  9.— Teuijierature-curve  of  a  continued  remittent  fever,  with  slowly  rising  and  gradually  falling  ourvt 

(typUoid  fever). 


Centigrade  (1.8°  F.)  in  half  an  hour.  Tliis  phenomenon  of  heat-produc- 
tion is  offset  by  one  of  heat-dispersion,  occurring  chiefly  through  the 
skiu,  lungs,  and  the  excreta.  Both  heat-production  and  heat-dispersion 
are  under  the  influence  of  the  nervous  system,  and  through  its  regula- 
tion of  both  processes  a  constant  temperature  is  maintained. 

On  exposure  to  lower  temperatures  the  heat-production  is  increased 
(chiefly  through  the  agency  of  the  muscles),  while  heat-dispersion  is 
lessened  through  contraction  of  the  cutaneous  vessels  and  inhibition  of 
perspiration. 

On  exposure  to  higher  temperatures  heat- dispersion  is  increased 
through  increased  frequency  of  respiration,  dilatation  of  the  arteries  of 
the  skin,  and  increased  secretion  of  sweat. 

In  those  conditions  which  we  call  fever  there  is  a  iliHturhance  of  the 
regulation  of  heat-production  and  h<'<(t-(lisperslon,  in  favor  of  heat-jn'oduc- 
tion,  so  that  the  tempemtuve  of  the  hodij  is  more  or  less  elevated  above  the 
normal  (Figs.  9-11).  Elevations  of  temiierature  (rectal  measurements) 
to  38=  0.  (100.4"  F.)  are  called  hijpernormal ;  from  38°  to  38.5°  C. 
(100.4-101.3°  F.),  light  fever;  from  38.5  to  39.5°  C.  (101.3-103.1°  F.), 
moderate  fever ;  39.5-40.5°  C.  (103.1-104.9°  F.),  marked  fever ;  over 
40.5""  C.  (104.9°  F.)  (evening  temperature),  high  fever ;  and  over  41°  C. 
(105.8°  F.),  -Ai^  hiiperpyrexia. 

Four  periods  may  l>e  distinguished  in  fever.  The  first,  which  is 
known  as  the  pyrogenetic  or  initial  stage  or  stadium  incrementi,  cor- 
responds to  that  time  during  which  tlu;  previously  normal  tcni]»cialure 
reaches  the  average  height  chaiacteiistic  of  the  disease.  This  i)eriod  is 
sometimes  short  (Fig.  10),  half  an  hour  to  two  hours  long,  and  in  this 
case  is  usually  accompanied  by  a  chill;  sometimes  longer  (Fig.  9),  one  to 
several  days,  and  then  usually  runs  its  course  without  a  chill,  though 
chilly  sensations  nuiy  repeatedly  occur. 


92 


THE    GENERALIZATION    OF    DISEASE. 


Ill  the  second  ]>eriod,  known  as  tlie  fastigium,  whose  duration  varies 
according  to  the  disease  from  a  few  hours  to  several  weeks,  the  tempera- 
ture reaches  one  or  sevenil  acme  I  He  hi ffhest  points,  between  which  there 
are  more  or  less  marked  remissions. 

In  the  stage  of  decline  of  the  fever  or  the  defervescence  or  stadium 
decrementi,  tlie  body-temperature  returns  again  to  the  normal.  If  this 
takes  place  through  a  rapid  fall  of  temperature  (Fig.  10),  it  is  called 
crisis  ;  if  slowly,  it  is  termed  lysis  (Fig.  9).  The  former  is  usually  ac-. 
companied  by  jjrofuse  sweating,  and  in  a  few  hours,  or  at  most  in  one' 
to  one  and  a  half  days,  the  temperature  falls  two  or  three  degrees,  occa- 
sionally as  much  as  five  to  six  degrees  Centigrade.     In  lysis  the  tempera- . 


■ 

ggggigsgjg  ill 

Fig.  10.— Temperature  curve  of  a  con- 
tinued fever  with  rapidly  ascending  and 
rapidly  falling  curve  (pneumonia). 


Fig.  11.— Temperature-curve  of  an  inter- 
mittent tertian  fever  (malaria). 


ture  falls  gradually  for  three  to  four  or  more  days ;  the  decline  may  be  , 
either  continuous  or  intermittent. 

The  boundary-line  between  fastigium  and  defervescence  is  not  always  ' 
sharply  defined,  and  before  the  latter  sets  in  there  may  occur  elevations  • 
of  temperature,  this  phenomenon  being  called  perturbatio  critica.  If 
between  the  fastigium  and  defervescence  there  occur  several  days  of 
uncertainty  Mith  striking  fluctuations  upward  or  downward,  such  period 
is  known  as  the  amphibolous  stage.  Occasionally  there  may  occur  a 
short  ])eriod  in  wliich  the  temperature  is  somewhat  lowered,  but  yet  re-: 
mains  higli  above  the  normal,  to  sink  after  a  few  days  to  the  normal' 
either  rapidly  or  by  a  gi-adual  decline. 

In  the  stage  of  convalescence  the  temperature  returns  to  the  normal 
condition.  The  heat-regulation  is  during  this  time  still  imperfect,  so 
that  often  si iglit  elevations  and  not  infrequently  subnormal  temperatures 
occur. 

If  during  the  course  of  a  fever  the  daily  variation  is  slight,  so  that 
the  ditfeTcnce  between  maximum  and  minimum  is  not  more  than  that 
under  noiinal  conditions,  the  fever  is  called  a  continuous  fever  (febtis 
r<»iti)n«()(V\<x.  10).  If  tlie  differences  are  greater,  the  fever  is  termed 
subcontinuous  ( frhri.s  siihroutinua),  remittent  fever  (fehris  remittens)' 
(Fig.  D),  or  intermittent  fever  (febris  intermittens)  (Fig.  11). 

In  the  last-named,  afebrile  periods  {apyrexia)  alternate  with  periods 
of  fever,  each  paroxysm  having  an  initial  period,  a  fastigium,  and  a 
defervescence.  In  the  infectious  disease  known  as  febris  recurrens  there: 
is  first  a  continuous  fever,  which  altera  few  days  falls  by  crisis ;  after 
about  a  week  or  so  a  second  rise  of  temperature  occurs,  which  may  be 
followed  by  a  second  stage  of  apyrexia,  and  this  by  a  third  period  of  fever. 

Many  diseases — such  as  typhoid  fever,  pneumonia,  measles,  relapsing! 


FEVER.  93 

fever,  etc. — are  characterized  by  a  ly{)ical  teinperalurc-curve;  others — 
as  pleuritis,  endocarditis,  dii)litheria,  tubercidosis,  i»hlej>inon,  etc. — have 
uo  typical  course  of  fever. 

The  elevation  of  the  body=temperature  in  fever  is  dependent  i^ri- 
marily  on  an  lnvnuse  in  Itcdt-production  t/ifoiif/li  inrrcd.sr  of  the  chnni<ud 
chuniU'S  occitrriiif/  in  the  Ixxli/.  Thi)  rr.sj)inili>fi/  intiTc/i(nif/r  of  (ja.sc.s — tlie 
excretion  of  carbonic  acid  and  the  tal<;in<;-ui)  of  oxy<;en — is  increased,  a 
proof  that  the  oxidation -processes  and  with  these  also  the  lieat-produc- 
tion  are  increased.  At  the  same  time  tlie  excretion  of  nitrof/enom  elements 
in  the  urine  (urea,  uric  acid,  creatinin)  /,v  increased — on  the  average  about 
from  seventy  to  one  hundred  per  cent,  under  certain  conditions  even  as 
much  as  threefold.  There  is  also  an  increased  destruction  of  the  albu- 
minoid substances  of  the  body,  the  albumin  of  the  organs,  even  in  the 
latent  period  of  the  fever. 

The  increase  of  heat-iiroduction  varies  in  different  fevers,  but  in  gen- 
eral does  not  reach  that  degree  which  can  be  produced  by  excessive 
muscle-actiou  and  over-feeding  with  albumin.  It  is  at  its  highest  point 
at  the  time  of  the  initial  chill,  in  that  the  violent  muscular  contractions 
thereby  produced  may  increase  the  production  of  heat. 

The  second  cause  of  the  elevation  of  the  body-temperature  is  deficient 
heat-dispersion.  At  the  height  of  the  fever  the  patient  as  a  rule  gives 
off  more  heat  than  the  normal  individual,  but  this  dispcisioii  is  not  sufti- 
cieut  to  offset  the  excessive  heat-production.  Heat-production  is  con- 
stantly increased ;  heat-dispersion  is  irregular. 

In  the  initial  stage  the  cutaneous  vessels  are  contracted  as  a  result  of 
i  stimulation  of  the  vasomotors,  the  skin  is  pale,  the  heat-dispersion 
I   slight,  under  certain  conditions  even  less  than  normal. 

Chills  occur  when,  through  the  contraction  of  the  peripheral  arteries, 
i  the  supply  of  blood,  and  consequently  the  heat-supply,  to  the  cutaneous 
j  nerves  is  suddenly  diminished,  while  in  the  interior  of  the  body  the  tem- 
perature is  rising. 
I  In  the  second  stage  of  fever  the  skin  is  often  hot  and  reddened,  and 
I  in  certain  diseases  sweating  occurs;  but  the  increased  heat-dispersior. 
I  thereby  produced  is  not  sufdcieut  to  lower  the  temperature  to  the  nor- 
!  mal.  The  increased  excitability  of  the  vasomotors  or  the  deficient  irri- 
i  tability  of  the  vaso-dilators  is  also  present  during  this  period,  and  as  a 
!  result  the  skin-temperature,  as  well  as  the  heat-dispersion,  varies  greatly. 
!  The  skin  is  at  times  pale  and  cold,  at  other  times  red  and  hot,  and  the 
i  hands  may  be  cold  while  the  trunk  is  hot.  The  centres  governing  hcat- 
i  dispersion  are  therefore  acting  faultily. 

i  In  the  period  of  defervescence  the  relations  of  heat -dispersion  and 
!  heat-production  are  changed  in  favor  of  the  former.  The  cutaneous  ves- 
!  sels  l)ecome  dilated,  the  skin  gives  out  a  great  amount  of  heat  from  the 
!  abundance  of  blood  circulating  through  it,  and  when  the  critical  fall  of 
I  the  fever  occurs  there  is  usually  ])i'ofuse  sweating. 

[  The  cause  of  fever  is  not  known  with  certainty,  yet  this  much  can  be 
1  said,  that  fever  is  most  fieiiuently  the  resuU  of  the  entrance  of  a  hannfitl 
'•■  agent  into  the  fluids  of  the  bodij.  In  many  cases  this  harmful  agent  arises 
demonstrably  from  a  local  focus — for  example,  from  erysipelatous  and 
I  phlegmonous  inflammations  of  the  skin.  Experimentally,  fever  may  be 
produced  by  very  different  procedures — for  example,  through  the  infu- 
I  sion  into  the  vessels  of  an  animal  of  blood  from  one  of  another  species, 
i  through  the  injection  of  aninml  or  vegetable  substances  that  are  begin- 
I   ning  to  decompose,  and  through  numeious  infect  ions.      In  man,  iho  infec- 


94  THE    GENERALIZATION    OF    DISEASE. 

fioKS  (lisrasrM,  wliicli  ai/e  regarded  as  due  to  specific  micro-orgauisms  mul- 
tiplying ill  tlie  body,  are  in  particular  cliaracterized  by  fever. 

it  is  probable  that  the  parasites  multiplying  within  the  body  cause  an 
increased  tissue-destruction,  either  directly  or  through  the  production  of 
unformed  ferments,  and  that  at  the  same  time  substances  are  produced 
which  act  n^jwisons  upon  the  central  nervous  system.  The  action  of  the 
latter  may  be  assumed  to  be  of  such  a  nature  that,  on  one  side,  t In- 
activity of  the  muscles  and  glands,  and  consequently  the  heat-producing 
metabolism,  are  increased;  while,  on  the  other  hand,  through  the  dimin 
islied  and  disturbed  functions  of  the  nerves  governing  sweating,  as  well 
as  of  the  vasomotors,  the  processes  of  heat -dispersion  fall  behind  those 
of  heat-production.  Further,  though  the  organism  makes  an  effort  to 
regulate  the  temi^erature,  it  is  no  longer  able  to  maintain  it  at  the  nor- 
mal level,  because  of  the  disturbances  of  the  regulating  apparatus. 
"What  share  in  the  increase  of  body-temperature  is  due  to  the  direct  ac- 
tion of  bacteria  and  of  the  ferments  formed  by  them,  or  what  share  is 
due  to  the  increase  of  metabolism,  through  the  stimulation  of  the  ner\  ts 
as  well  as  by  disturbance  of  heat-dispersion,  cannot  at  present  be  deter- 
mined. It  IS,  however,  certain  that  the  factors  vary  in  different  cases. 
That  under  certain  conditions,  changes  in  the  nervous  system  without 
contamination  of  the  tissue- juices  are  in  themselves  sufficient  to  cause  a 
feverish  increase  of  temperature,  is  shown  by  the  fact  that  fever  may 
occur  in  epileptic  attacks,  in  the  periods  of  excitation  occurring  in  the 
course  of  i^rogressive  paralysis,  after  severe  frights,  after  the  passage  of 
a  catheter  into  the  bladder,  etc.  According  to  the  investigations  of 
Eichet,  Aronsohn,  and  Sachs,  a  marked  increase  in  body-temperature 
with  increase  of  the  respiratory  interchanges  of  gases  and  increased  ex- 
cretion of  nitrogen  (Aronsohn  and  Sachs)  may  be  produced  in  animals 
by  a  puncture  which  passes  through  the  cerebral  cortex  and  strikes  the 
corpus  striatum.  The  same  phenomenon  may  be  produced  also  by  elec- 
trical stimulation  (Aronsohn,  Sachs)  of  the  same  portion  of  the  brain. 
Xevertheless,  fevers  dependent  upon  nervous  disturbance  are  rare,  and 
are  overshadowed  in  importance  by  those  caused  by  infection. 

The  I'ise  of  temperature  in  fever  is  usually  accompanied  by  an  in= 
crease  in  the  frequency  of  the  pulse=rate  ;  but  in  some  cases  this  elfect 
of  the  elevation  of  temperature  may  be  so  greatly  modified  through 
stimulation  of  the  vagus — as,  for  example,  in  basilar  meningitis — that 
the  pulse-rate  may  be  lowered.  The  pulse  is  at  one  time  full  and  bound- 
ing, at  another  time  small  because  of  weakened  contractions  of  the  heart. 

The  impairment  of  the  contractions  of  the  heart-muscle  is  dependent 
l)artly  upon  the  constant  high  temperature,  partly  upon  poisonous  sub- 
stances, Avhich  are  produced  by  the  morbid  processes  peculiar  to  the  es- 
l)e<ial  disease,  and  which  exert  a  harmful  influence  upon  the  muscle- 
substance  of  the  heart  or  upon  the  nervous  system. 

In  diseases  accompanied  by  fever  there  is  usually  a  marked  sensation 
of  illness  with  a  heavy  feeling  in  the  head.  In  severe  fevers  there  occur 
clouding  of  consciousness,  symptoms  of  excitation  and  depression,  hal- 
lucinations, delirium,  apathy,  involuntary  evacuations,  tremors  of  the 
hands,  convulsions  (in  children),  etc.  The  muscles  of  the  body  become 
weak  and  not  infreciuently  painful.  Digestion  is  decidedly  impaired; 
the  appetite  for  food  is  slight,  but  on  the  contrary  there  is  great  thirst; 
the  mouth  is  dry.  There  is  an  increased  frequency  of  respiration  ;  after 
the  api)earance  of  muscular  weakness  the  respiratory  movements  are 
superficial.     The  excretion  of  urine  is  usually  diminished ;  the  amount 


FEVER.  05 

of  urea  in  the  urine  is  iucroased,  wnil«>  that  of  sodium  cl'Joriih^  is  <limiii- 
ished. 

In  prolonged  fevers  there  is  marked  Avastiiii;-  of  (lie  body,  in  that  a 
large  portion  of  the  albuminous  material  and  fat  of  tlie  body  is  de- 
stroyed. 

To  what  extent  these  symptoms  in  individual  cases  are  d«»pendent 
upon  the  increase  of  temperature  or  to  what  extent  upon  the  damage  to 
the  organism  caused  by  the  specific  morbid  process,  it  is  dillicult  to  say, 
but  the  marked  effects  upon  the  nervous  system  must  for  the  greater 
part  be  regarded  as  a  result  of  the  infection  and  intoxication. 

Death  results  most  often  from  cardiac  insufticicncy,  but  it  may  be 
brought  about  also  by  the  severity  of  the  infection  and  the  intoxication, 
by  the  wasting  of  the  streugth,  as  well  as  bv  an  excessive  elevation  of 
temperature  to  43°,  44°,  or  45°  C.  (109.4°;  111.2°,  and  113°  F.).  It 
should,  however,  be  remarked  that  under  certain  conditions  very  high 
temperatures  may  be  borne  for  a  length  of  time  Mithout  fatal  results, 
and  that  the  death  following  very  high  temperatures  cannot  be  ascribed 
to  the  abnormal  temperature  alone,  but  is  rather  to  be  regarded  in  part 
or  wholly  as  the  result  of  the  infection  (see  §  3). 

The  questions  coucerniug  the  nature  of  fever,  which  Galen,  designated  as  Color 
prater  naturam,  have  been  much  advanced  during  the  last  decades  by  numerous  clin- 
ical and  experimental  investigations.  From  these  we  have  learned  of  the  associated 
disturbances  of  metabolism,  the  increased  consumption  of  oxygen,  the  increased  excre- 
tion of  nitrogen  and  carbon  compounds,  as  well  as  of  the  distiu'bances  of  the  heat-dis- 
persioii.  If  we,  in  spite  of  this  knowledge,  do  not  yet  possess  a  full  understanding  of 
all  the  morbid  processes  which  in  a  given  case  may  cause  fever,  we  may  attribute  this 
''■  tlie  fact  that  the  causa  efflciens  of  fever  is  not  a  single  entity,  but  may  be  one  of 
many  different  factors,  and  that  the  feverish  elevation  of  the  body-temperature  does 
nut  always  occur  in  exactly  the  same  manner.  The  increase  of  the  tissue-changes  and 
nxidation-processes  witliin  the  body  is  not  always  brought  about  in  the  same  way. 
Fiirtlu-r,  the  disturbance  of  heat-dispersion  through  radiation  from  the  skin  and  the 
evaporation  of  water  is  not  always  the  same,  but  changes,  not  only  in  the  course  of  one 
tVbrile  disease,  but  also  in  different  forms  of  fever.  Correspondingly,  the  role  played 
by  the  nervous  sj'stem  in  the  occurrence  of  the  feverish  increase  of  temperature  is  not 
tlic  same  in  every  case.  According  to  Aronson,  the  essential  feature  of  fever  is  a 
patliDlogical  increased  stimulation  of  the  heat-centres  whereby  the  motor-trophic  ap- 
paratus of  the  body  muscles  is  excited  to  an  increased  production  of  heat  and  to  changes 
in  the  heat-dispersion.  The  different  types  of  fever  are  determined  by  the  different 
kinds  of  stimuli,  which  in  the  infectious  diseases  are  especiall}'  manifold.  The  founda- 
tion type  is  an  elevation  of  the  body-temperature  in  the  absence  of  any  other  disease  of 
the  biiily,  and  caused  solely  by  a  direct  mechanical,  electrical,  or  chemical  stiniuhition  of 
till'  heat-centre.  According  to  Senator,  there  is,  in  fevers,  no  harmony  between  the 
ii  gulation  of  heat  and  metabolism ;  and  we  must  therefore  assume  that  heat  is  developed 
tlirough  other  processes  than  those  leading  to  the  production  of  urea  and  carbonic  acid. 
A(  fording  to  Herz,  heat  is  set  free  by  the  changes  in  the  arrangement  of  the  molecules 
of  tlic  cell-protoplasm,  which  occur  in  many  of  the  cells  in  fever  patients,  and  which 
li'ad  to  liie  destruction  of  protoplasm.  Further,  heat  may  be  liberated  by  processes  of 
swelling  and  coagulation  of  the  protoplasm,  while  at  the  same  time  the  diminished  ac- 
tivity of  the  regenerative  processes  in  fever  occasions  a  loss  in  the  storing-up  of  latent 
heat.  On  the  other  hand,  Krehl  and  Matthes  are  of  the  opinion  that  oxidation  forms 
the  sole  source  of  heat. 

Literature. 

{Fever.) 

Aronson:  Das  Wesen  des  Fiebers.     B.  med.  Woeli.,  1002. 

Aronson   u.    Sachs:  Beziehungen   d.    Gehirns    /.ur   Kiupcrwilrnie    u.    zuni    Fic'ber. 

I'll  tiger's  Arch.,  37  Bd.,  1885. 
Bouchard:  Lemons  sur  les  auto-intoxications  dans  les  maladies,  Paris,  1889. 
Colinheim:  Vorlesungen  liber  allgemeiue  Pathologic,  ii.,  Berlin,  1882. 


96  THE    GENERALIZATION    OF    DISEASE. 

Finkler:  Ptltiscrs  Arcli.,  xxvii.;  Ueber  das  Fieber,  Bonn,  1882. 

Franke  :  Die  meuschlicbe  Zelle,  Leipzig,  1893. 

Gangoiphe  ci  Courmont:  L;i  liC-vre  cousec.  a  1' obliteration  vasculairc.      Arch.  dB 

iiR-d.  cxp.,  iii..  llSUl. 
Girard:  L'inflviciice  du  cerveau  sur  la  cbaleur  animale.     Arch.  d.  pbys.,  viii.,  1886. 
Glax :  Ueber  die  Wassenetention  ini  Fieber,  Jena,  1894. 
Guyon:  L'livpcrtliermie   centrale,  consec.  aux  les.   du  cerveaii.    Arch.    med.    exp.j 

1S94. 
Hammersohlag:  Bezieh.  des  Fibrinfermentes  zum  Fieber.     Arch.  f.  exp.  Path.,  2'| 

B(i..  1890. 
Herz:   Untcrsuchungen  iiber  Warme  und  Fieber,  Wien,  1893. 
Jurgensen:  Die  Korperwiirme  des  gesunden  Menschen,  Leipzig,  1878. 
Krehl:  Patbologische  Physiologie,  Leipzig,  1898. 
Krehl  u.    Matthes:  Entstehuns;  der   Temperatursteigenmg  des   tiebernden  Ore 

isimis.    Arch.  f.  exp.  Path.,  38  Bd.,  1897 (Lit.);  Eiweisszerfall,  ib.,  40  Bd.,  1898. 
Leyden:  Kespiration  im  Fieber.     Deut.  Arch.  f.  klin.  Med.,  v.,  vii.,  1870. 
Liebermeister :  Pathol,  u.  Ther.  d.  Fiebers,  Leipzig,   1875;   Specielle  Pathol.,  Leip' 

zig,  18S7. 
Lowit :  Die  Lehre  vom  Fieber,  Jena,  1897. 

Loewy:  Stoflfwechseluntersuchungen  im  Fieber.     Virch.  Arch..  126  Bd.,  1891. 
May:  Der  Stoflfwechsel  im  Fieber.     Zeitschr.  f.  Biol.,  30  Bd.,  1893. 
Mosso:  Influence  du  systeme   nerveux    sur  la  temperature  animale.     Arch.  ital.  d 

biol.,   vii.,  1886;  Virch.    Arch.,  106  Bd. ;   La  doctrine  de  la  fievre  et  les  ccntu 

thormiques  cerebraux.     Arch.  ital.  de  biol.,  xiii.,  1890. 
Murri:  Sulla  teoria  della  febbre,  Fermo,  1874. 
Naunyn:    Experimentelles    zur  Lehre    vom   Fieber.     Arch.    f.    exp.    Path.,  xviii 

is,s4  (Lit.). 
V.  Noorden:  Pathologie  des  Stoffwechsels,  Berlin,  1893. 
Rabe:  Die  modernen  Fiebertheorieen,  Berlin,  1894. 
Rosenthal:  AViirmeproduction  im  Fieber.     Biol.  Cbl.,  xi..  1891. 
Roussy :  Kech.  exp.  sur  la  pathogenic  de  la  fievre.     Arch,  de  phvs.,  ii.,  1890. 
Sarbo:  Ueber  hysterisches  Fieber.     Arch.  f.  Psych.,  23  Bd.,  189l'. 
Schultze:  "Witrmehaushalt  nach  dem  Wiirmestich.     Arch.  f.  exp.  Path.,  43  Bd.,  1S9! 
Senator:  Unters.  liber  den  fieberh.  Process,  Berlin,   1873;  Arch.  f.  Anat.  u.  Phvs 

1S72.  ■    . 

Stern:  Warmeregulation  im  Fieber.     Zeitschr.  f.  klin.  Med.,  20  Bd.,  1892.  i 

Ughetti:  Das  Fieber.  Jena,  1895  (Lit.).  \ 

Unverricht :  Ueber  das  Fieber,  Leipzig,  1898.  ! 

Volkmann  u.  Genzmer:  Septisches  u.  asept.  "Wundfieber.     Samml.  klin.  Yortr.,  N<: 

121,  1877. 
Welch:  On  the  General  Pathology  of  Fever,  Philadelphia,  1888. 
Wunderlich:  Das  Verhalten  der  Eigenwarme  in  Krankheiten,  Leipzig,  1870. 
Zunz :  Ueber  den  Stoflfwechsel  fiebernder  Thiere.     Arch,  f .  Psych.    1882. 


CHAPTER  III. 

The  Protective  and  Healing  Forces  of  the  Human 
Body.     The  Acquiring  of  Immunity. 

I,    The    Natural    Protective    Contrivances,     Protective    Forces,    and 
Healing  Powers  of  the  Human  Organism,  and  their  Action. 

§  29.  The  human  orgauism  is  not  entirely  defenceless  against  the 
mauy  harmful  influences  to  which  men  during  the  course  of  their  lives 
are  exposed.  It  possesses  various  protective  contrivances  and  pro- 
tective forces,  by  which  it  is  able  in  many  cases  to  ward  off  the  injuri- 
ous agent,  or  at  least  rapidly  to  counteract  its  harmful  influence,  so  that 
a  disease  may  be  either  wholly  prevented  or  confined  to  a  slight  local 
lesion  of  much  less  severity  than  the  disease  usually  produced  by  the 
particuhir  injurious  agent.  As  the  mode  of  action  of  different  injurious 
influences  varies  greatly,  so  does  the  manner  of  defence  likewise  vary 
greatly.  The  protective  forces  may  act  at  very  different  times — that  is, 
sometimes  even  before  the  tissues  have  been  damaged,  at  other  times 
after  the  injurious  action  has  reached  a  certain  stage,  and  threatens, 
either  through  direct  extension  or  through  metastasis,  or  through  poison- 
ing of  the  body-fluids,  or  through  disturbance  of  function,  to  spread 
further  through  the  body. 

When  the  environment  of  the  body  becomes  relatively  cold  or  rela- 
tively warm,  those  regulating  functions  are  brought  into  play  through 
which  the  organism  can  increase  or  diminish  heat-production  and  heat-dis- 
persion, and  in  this  manner  protect  itself  within  certain  limits  against 
the  influence  of  the  external  temperature.  If  these  regulating  functions 
are  imperfectly  performed,  as  in  consequence  of  alcoholic  intoxication, 
the  individual  may  more  easily  die  from  the  effects  of  cold  than  when 
under  normal  conditions. 

We  cannot  speak  of  special  protecting  contrivances  against  gross 
mechanical  influences ;  yet  it  is  to  be  noted  that  the  tissues  by  virtue  of 
idieir  physical  properties  are  fitted  to  offer  resistance  to  numerous  forms 
of  traumatism  without  receiving  injury.  If  small,  firm  bodies,  such  as 
lust -particles,  reach  the  mucous  membrane  of  the  respiratory  or  intes- 
tinal tracts,  the  epithelium  forms  a  protective  barrier  against  their  en- 
rance  into  the  tissue-spaces.  Further,  if  ciliated  epithelium  is  i)resent, 
he  dust-particles  may  be  carried  away  by  the  nioremrnts  of  the  cilia,  or 
:hey  may  become  surrounded  by  the  mucus  produced  by  the  epithelium 
iud  mucous  glands,  and  in  this  way  are  tiansported  out  of  the  body. 

Not  infrequently  there  appear  cells  on  the  surface  of  the  mucous 
3iembrane  which  encompass  the  dust-particles,  and,  taking  these  up  into 
heir  substance,  are  carried  away  with  the  secretion  of  the  mucous  mem- 
brane. This  phenomenon,  known  as  phagocytosis,  is  observed  on  the 
nucous  membranes  of  the  ])harynx  and  respiratory  tract  and  in  the 
ilveoli  of  the  lungs.  The  active  agents  participating  in  it  are  not  only 
7  97 


98  THE    PROTECTIVE    POWERS    OF   THE    BODY. 


the  wanderiug-cells  -which  pass  from  the  tissues  to  the  surface,  and  are' 
derived  chietly  from  the  blood-vessels  and  also  from  the  nodes  o1 
Ij'mphadenoid  tissue  in  the  mucous  membrane,  but  epithelial  cells  a^ 
well.  The  peculiar  phenomenon  of  phagocytosis  depends  upon  the  fac^ 
that  the  cells  can,  by  movements  of  their  protoplasm,  take  up  little  par 
tides,  Avhich,  like  insoluble  dust,  exert  no  harmful  influence  upon  th(; 
cell-piotoplasm.  If  these  cells  laden  with  dust  pass  outside  of  the  body' 
the  taking-up  of  the  dust  by  the  cells  appears  to  be  a  useful  activity 
which  aids  in  the  cleansing  of  the  organs  from  dust.  If  the  dust-lader 
cells,  on  the  other  hand,  as  hapi^ens  particularly  in  the  lungs,  pass  int(| 
the  lymijh-chaunels  and  are  deposited  along  their  walls  or  are  carried  U 
the  lymph-glands — that  is,  if  a  metastasis  of  the  dust-containing  cell 
into  the  internal  organs  takes  place — the  taking-up  of  dust  by  these  cell: 
appears  in  a  less  favorable  light;  and  we  can  regard  this  act  as  a  usefu 
phenomenon  only  through  the  consideration  that  the  infiltration  of  th; 
pulmonary  connective  tissue  and  lymph-glands  M'ith  dust  is  less  harmfui 
than  the  deposit  of  dust  on  the  inner  surface  of  the  alveoli. 

When  dust-particles,  free  or  enclosed  in  cells,  reach  the  lymph-glandi^ 
they  are  arrested  and  deposited  in  the  cells  of  these  glands,  so  that  th' 
lymph-glands  may  be  regarded  as  trustworthy  Jilters,  which  guard  th! 
blood  and  the  internal  organs  from  the  entrance  of  dust.  ■ 

Against  the  action  of  poisons  the  human  body  is  able  to  protect  itsel. 
in  various  ways.  In  the  case  of  corrosive  i)oisons  the  liorny  layer  of  th: 
epidermis  and  the  mucus  of  the  mucous  membranes  offer  a  certain  pre- 
tectiou ;  and  under  certain  conditions  a  marked  increase  in  the  prodmj 
tion  of  mucus  —  in  the  stomach,  for  example  —  may  greatly  diminisj 
the  harmful  effects  of  a  corrosive  fluid.  Through  a  transudation  of  fluij 
from  the  blood-vessels  on  to  the  surface  of  the  mucous  membrane  j 
caustic  fluid  may  be  so  diluted  as  to  modify  its  action.  On  the  oth(j 
hand,  the  injurious  substance  may  be  thus  spread  over  a  greater  surfac* 
and  thereby  cause  a  more  widespread  damage  to  the  tissue.  j 

On  many  poisons,  abrin,  ricin,  the  toxins  of  cholera,  tetanus,  arj 
diphtheria,  and  snake-venom,  the  digestive  juices  have  such  an  influeun 
that  doses  invariably  fatal  when  injected  under  the  skin  may  be  borij 
with  impunity  when  taken  by  the  mouth.  According  to  Eansoij 
guinea-pigs  are  able  to  withstand,  when  administered  by  the  mouth,  £■ 
amount  of  tetauotoxiu  equivalent  to  three  hundred  thousand  times  tli 
minimal  fatal  dose.  According  to  ISTencki  and  others,  this  neutraUzatid 
of  the  jwison  is  produced  hy  the  digestive  enzymes,  at  one  time  chiefly  throuji 
the  i)epsin,  at  another  time  through  the  trypsin  and  the  mixture  of  tli 
pancreatic  juice  with  the  bile.  It  is  probable  (K^eucki)  that  the  digesj 
ive  enzymes  cause  a  slight  change  in  the  molecules  of  the  toxin,  simil; 
to  the  change  of  albumin  into  albumose;  and  the  products  arising  fro| 
the  toxins  may  accordingly  be  termed  toxoses  or  toxoids.  The  intestinj 
enzymes  have  no  neutralizing  influence  in  the  case  of  sausage-,  meal; 
fish-,  bean-,  pea-,  etc.,  poisoning  produced  hy  the  Bacillus  botuUmis ,-  an. 
tlicivfore,  after  tlie  eating  of  such  infected  foods  severe  and  fatal  intoj' 
cations  may  occur.  ' 

In  the  case  of  those  i)oisons  which  after  their  entrance  into  the  bod 
juices  act  injuriously  upon  the  blood  or  the  ner\'ous  system,  a  favorabi 
counter-action  on  the  part  of  the  organism  may  be  given  partly  by  :- 
rapid  excretion  of  the  poison  through  the  kidneys,  liver,  intestine,  pan- 
creas, salivary  glands,  mammary  glands,  sweat  glands,  and  lungs;  parlf 
through  their  transformation  into  combinations  soluble  tvith  difficulty,  whii 


1 


NATURAL    IINIM UNITY.  99 

are  thus  stored  up  in  ditfereut  organs  (liver),  and  partly  throuffh  a  chour/e 
of  the  jioisons  into  combiiiatious  tJiat  arc  relativdy  harmlcsfi  and  casili/  .soluh/r, 
(vhich  are  then  taken  up  into  the  circulation  and  excreted,  and  partly 
through  a  chemical  change  of  the  poison. 

Of  natural  immunitji  a;iainst  poisons  or  natur(d  resistance  to  poisons  we 
tkuow  but  little  at  present,  yet  there  is  no  doMl)t  tliat many  ])()isons  are 
])oisonous  only  for  certain  organisms,  and  it  is  probable  tlial  man  is  re- 
sistant to  many  poisons  which  are  injurious  to  certain  animals.  The 
same  thing  holds  true  especially  of  the  toxins  (§  11),  such  as  are  formed 
iby  bacteria  or  by  higher  aninuils  (snakes)  and  plants  (riciu  and  abrin). 
If  we  consider  that  many  animals  are  only  slightly  or  not  at  all  suscepti- 
ble to  poisons  which  have  marked  action  upou  the  human  bod\- — for 
:exanii)le,  the  hedgehog  is  immune  or  resistant  tocantharidin  and  the  bite 
of  i>oisonons  snakes  respectively ;  birds  are  immune  against  atropine  and 
opinm;  goats  against  lead  and  nicotine;  while  dogs,  rats,  or  other  ani- 
mals used  for  experiment  show  a  disproportionately  greater  resistance  to 
Itacterial  poisons  or  plant-alkaloids  thau  does  man— so  it  is  very  prob- 
able that  the  reverse  is  also  true.  The  natural  immunity  of  man  against 
iiiany  of  the  infectious  diseases  of  animals  must  depeud  upon  a  resistance 
ito  tiie  toxins  produced  by  the  particular  bacteria.  According  to 
Ehrlich,  this  resistance  to  poisons  may  be  explained  by  the  theoiy  that 
the  particular  toxin  possesses  no  chemical  relationship  to  any  one  of  the 
^hody  elements.  A  relative  immunity  may  therefore  depend  upon  the 
,fact  that  the  healthy  individual  possesses  already  a  certain  amount  of 
antitoxin  (for  example,  against  diphtheria  toxin). 

Fromm  has  recently  briefly  summarized  our  knowledge  concerning  the  chemical 
"protective  resources  of  the  animal  body  in  intoxications.  Inorganic  poisons  are  rendered 
harmless  chiefly  by  three  kinds  of  chemical  action — oxidation,  reduction,  and  combina- 
tion with  a  protective  body  with  liberation  of  water.  Phosphates  and  sulphides  are 
oxidized  so  that  phosphoric  acid  and  sulphuric  acid  arise  which  are  neutralized  and 
excreted.  The  iodates  and  chlorates  are  changed  into  the  easily  solul)le  and  less 
poisonous  iodides  and  chlorides  which  are  then  excreted.  The  metallic  salts  and 
luetallic  oxides  are  converted  into  albuminates  (the  salt-like  combination  of  metallic 
.fixide  and  allnunin)  or  into  sulphides.  Inorganic  acids  are  combined  through  alkalies 
,and  changed  into  less  poisonous  salts. 

Organic  poisons  are  transformed  into  non-poisonous  substances  through  oxida- 
'tion,  reduction,  the  liberation  or  the  taking  up  of  water.  Often  several  reactions  follow 
lone  another;  usually  the  product  arising  through  oxidation  or  reduction  is  combined 
|to  one  or  more  other  substances  with  the  liberation  of  water.  Such  protective  sub- 
jstances  are  represented  particularly  by  the  sulphates  arising  through  the  disintegra- 
tion and  oxidation  of  albumin,  by  glycocoll  arising  in  the  breaking  down  of  albumin, 
Iglycuronic  acid  arising  through  the  oxidation  of  the  carbohydrates,  and  perhaps  also 
,'urea. 

Poisonous  acids  of  the  fat  series  are  oxidized  to  carbonic  acid  and  water.  Phenol 
land  those  bodies  which  through  oxidation  pass  directly  into  phenol  are  through  a 
^combination  with  sulphuric  acid  made  soluble,  harmless,  and  capable  of  being  excreted; 
'for  example,  phenol  is  excreted  as  potassium-phenol-sulphate;  benzoic  acid  and  its 
•oxidation  products  and  those  substances  that  are  transformed  directly  into  benzoic 
^acid  or  their  derivatives  are  combined  by  glycocoll;  trimethyl  carbinol,  naphthol.and 
^chloral  hydrate  appear  in  the  urine  combined  with  glycuronic  acid,  chloral  hydrate 
after  its  transformation  into  trichlorethyl  alcohol. 

Literature. 

(The  Action  of  Digestive  Juices  upon  Toxins.) 

Charrin:   Action  des  sues  digestifs  sur  les  poisons  microb.     Arch.  d.  phys.,  x.,   1898. 
Fraser:  Remarks  on  the  Antivenomous  Properties  of  the  Bile.     Brit.  Med.   Journ., 
1897. 


100  THE    PROTECTIVE    POWERS    OF    THE    BODY. 

Fromm :   Die  chemischen  Schutzmittel  d.  Thierkorp.  bei  Vergiftungen,  Strassburg,  190i 

(Lit.). 
Nencki,  Sieber  11.  Schoumow:  Entgiftung  d.  Toxine  durch  Verdauungssafte.     Ctb 

f.  Bakt.,  xxiii.,  1898. 
Ransom:   Das  Schicksal   des  Tetanusgifte.s   nach   seiner   intestinalen  Einverleibunf 

Deut.  nied.  Woch.,  1898. 

§  30.   Against  the  infections  and  intoxications  caused  by  parasite 

the  hiuuiui  oroanisiu  i)osse.sses  various  protective  contrivances  aii' 
powers  of  defence;  and  these  play  a  very  important  role  in  the  discusc 
caused  by  bacteria.  In  the  first  place,  man  possesses  a  natural  immu, 
nity  against  many  of  the  micro-oi'ganisms  pathogenic  for  animals  (fo 
example,  swine  plague,  swine-erysipelas,  cattle-plague,  symptomati 
anthrax ),  so  that  the  given  micro-organisms  are  not  able  to  reproduc 
within  the  body,  either  because  they  do  not  find  in  human  tissues  th 
necessary  conditions  of  life,  or  because  the  presence  of  certain  chemical  1 
active  substances  hinders  their  increase  or  kills  them  directly.  Fuitlici 
immunity  may  also  rest  upon  the  simple  fact  that  the  poisons  produce 
by  given  bacteria  in  a  given  organism  are  inactive  because  no  cheniic; 
affinity  or  relationship  exists  between  the  poisons  and  any  one  of  tb 
body  elements.  For  the  protection  of  the  body  against  the  pathogen! 
micro=organisms  there  are  available  certain  protective  forces,  whicb 
according  to  their  action,  maybe  divided  into  four  groups:  the  first  liii 
dering  the  entrance  of  bacteria  into  the  tissues;  the  second  hinderiii 
the  unlimited  local  spread  of  those  bacteria  which  have  gained  eutrautw, 
and  have  begun  to  multiply ;  the  third  preventing  the  entrance  of  batfl 
teria  into  the  blood  and  their  metastasis;  the  fourth  hindering  intoxicH 
tion,  or  at  least  weakening  it,  and  reducing  it  to  a  low  degree.  | 

For  the  prevention  of  the  entrance  of  pathogenic  bacteria  into  thi 
tissues  the  same  properties  of  tissues  are  effective  as  those  hindering  tl,' 
entrance  of  dust;  and  in  such  capacity  the  jj^'otec^/ve  ej) Ith elium  sindtl\ 
amicus  play  a  very  important  role.  In  the  respiratory  tract  the  movj  *i 
7)ients  of  the  ciliated  epithelimn  also  furnish  protection,  and  in  the  stomacj 
the  poisonous  action  of  the  gastric  juice  upon  many  pathogenic  bacteria 
an  efficient  means  of  defence.  There  can  be  no  doubt  that  many  path<, 
genie  bacteria  are  not  able  to  penetrate  into  the  tissues,  not  only  througj 
the  uninjured  external  skin,  but  also  through  an  unwounded  mucov 
membrane,  without  some  assistance  favoring  colonization  and  reprodui 
tion,  and  that  the  stomach  secretion  not  infrequently  hinders  the  activil; 
of  the  bacteria  (pneumococcus,  cholera  spirillum),  or  even  kills  them. 

It  appears  also  that  the  mucus  secreted  by  the  mucous  membranes  \x^\ 
only  can  envelop  the  bacteria,  hinder  their  entrance  into  the  tissue,  ar* 
favor  their  removal,  but  that — what  is  of  much  greater  importance — tl 
mucus  acts  ui)on  the  bacteria,  causing  them  to  degenerate,  either  in  th: 
it  contains  sul>stances  which  are  injuiious  to  the  bacteria  or  in  that , 
oilers  an  unfavorable  medium  for  the  growth  of  the  bacteria.  In  th 
way,  according  to  Sanarelli  and  Dittrich,  pus-cocci,  cholera-spirilla,  ai' 
pneumococci  gi-adually  lose  their  virulence  and  die  in  the  mucus  of  tit 
mouth-cavity,  Avhile  diphtheria-bacilli  and  tubercle-bacilli  apparent! 
are  not  injured  by  mucus.  In  the  secretions  of  the  vagina  and  uterii 
various  kinds  of  bacteria  likewise  soon  die. 

In  the  intestine  the  hactrria  normally  i^resent  there  (B.  coli  communi 
li.  lact  is  aerogenes)  afford  an  effective  protection  against  the  multiplicati<j 
of  any  pathogenic  bacteria  that  may  happen  to  be  present;  for  exampl 
against  diphtheria  and  tetanus  bacilli  and  against  cholera-spirilla,  whil 


TROTKCTION    AGAINST    INFECTIOX.  lOT 

on  the  other  hand,  the  development  of  staphylococci  and  streptococci 
does  not  appear  to  be  hindered  by  tliem. 

Not  every  pathoi;enic  organism,  therefore,  which  j^ains  a  foothold 
upon  the  skin  or  upon  any  of  the  accessible  mucous  membranes  or  ji,ains 
eutrance  into  the  intestines  or  the  lun.i;s  ])roduces  an  infection.  It  has 
been  shown  throuiih  repeated  invest  illations  that  in  normal  individuals 
there  not  infre<iuently  occur  in  the  upi>ei'  res])iratoi'v  passa.u'es  and  mouth- 
cavity  not  only  harmless  bacteria — i.e.,  those  wliicli  caniiol  reproduce  in 
human  tissues — but  also  those  Mhich  can  undoubtedly  produce  disea.se, 
as,  for  example,  cocci  which  cause  supi)uratiou  or  thost^  whicli  are  able 
to  cause  croupous  iutlamnuition  of  the  luu<;-.  It  must,  therefore,  l)e 
jjranted  that  bacteriai  which  are  found  upon  the  mucous  meud)ranes  and 
have  perhai)S  multiplied  there  often  die  and  are  carried  away  without 
having  produced  infection.  This  occurs  especially  in  the  case  of  the 
cocci  above  mentioned,  and  tubercle-bacilli,  as  Avell  as  in  the  case  of 
cholera-spirilla  which  suffer  when  brought  into  contact  Mith  the  acid 
secretions  of  the  stomach.  Finally,  it  may  also  be  assumed  that  of  the 
pathogenic  bacteria  entering  the  alveoli  of  tlu^  lung  in  the  inspired  aii-, 
iiuany  do  not  reproduce,  but  die. 

When  bacteria  have  succeeded  in  gaining  entrance  locally  and 
have  begun  to  multiply— no  matter  whether  they  have  passed  through 
the  epithelium  without  the  aid  of  any  other  intiuence  (typhoid-bacilli, 
cholera-spirilla ),  or  whether  they  have  passed  into  the  connective  tissues 
through  the  medium  of  small  wounds  (tetanus-bacilli,  pus-cocci,  tubercle- 
■l)acilli) — if  they  produce  further  effects  either  through  local  destruction 
•of  tissue  or  through  the  poisoning  of  the  fluids  of  the  body,  there  may 
be  brought  into  action  on  the  part  of  the  body  certain  counter=influences 
irhich  either  hinder  the  further  development  of  the  bacteria  or  weaken  or  even 
rompletehj  destroy  the  poisons  produced  by  them.  The  first-named  restraining 
linfluence  must  naturally  depend  upon  local  conditions,  either  upon  vital 
tissue -processes  or  upon  the  effects  of  chemical  substances. 
i  As  previously  mentioned,  the  development  of  bacterial  colonies  gives 
[rise  to  local  tissue-degenerations,  inflammation,  and  tissue-proliferations 
' — all  of  which  are  processes  in  which  the  amount  and  composition  of  tlie 
llluids  found  in  the  affected  region,  as  well  as  the  cells  themselves,  are 
i.-haiiged.  Since  in  some  of  these  cases  a  destruction  of  the  bacteria  has 
ibeen  observed,  and  the  infection  not  infrequently  comes  to  an  end 
through  the  complete  disappearance  of  the  bacteria,  the  death  of  the 
matter  must  be  regarded  as  dependent  upon  local  conditions. 
j  Many  writers  ascribe  the  prevention  of  the  further  spread  of  the 
Imfection  and  the  destruction  of  the  bacteria,  in  local  foci  of  gi'owth,  to 
he  activity  of  cells  whicli  collect  at  the  seat  of  infection  and  take  up  the 
|)acteria  into  their  protoplasm — that  is,  to  phagocytosis  is  ascribed  the 
inost  imi^ortant  role  in  the  protection  of  the  body  against  bacterial  in- 
t'asion.  According  to  Metschnikoff  and  others,  the  aiiueboid  <"ells  of  tlie 
l)ody  carry  on  a  fight  against  the  foreign  invaders  and  endeavor  to  over- 
come them  and  destroy  them.  Such  a  characterization  of  the  phenomena 
|)f  phagocytosis  is  not  supi:)orted  by  the  actual  facts,  and  can  Ik's  regarded 
iinly  as  a  poetical  manner  of  expression  by  which  consciousness  a:id  will- 
)0wer  are  attributed  to  the  anueboid  cells  of  the  body  (the  leucocytes 
iud  the  proliferating  tissue-cells) — which  attributes  it  is  evident  do  not 
ixist.  Scientifically  considered,  the  gathering  of  tlu;  cells  at  the  iid'ected 
iocns  and  the  resulting  phagocytosis  repi-esent  simply  an  expression  of 
iertaiu  processes  which  are  natural  to  the  ama'boid  cells,  and  which  are 


'.  102    . .    •  •  :  ,  ,THE    PROTECTIVE    POWERS    OF    THE    BODY. 

dependent  upon  the  fact  that  the  cells  under  the  influence  of  mechanical, 
chemical,  and  thermal  influences  perform  certain  definite  movements. 
We  know  through  numerous  investigations  that  the  motile  cells  of  the 
body  are  in  part  attracted,  in  part  repelled  or  paralyzed  by  means  ol 
chemical  snbstancesin  certain  concentrations  of  solution  (seethe  Chapte) 
on  Inflammation);  and,  further,  that  contact  with  hard  bodies  can  stim: 
ulate  tliom  to  the  sending-out  of  jirotoplasmic  processes.  : 

Such  phenomena  are  designated  as  negative  and  positive  chemo- 
tropismus  or  chemotaxis  and  as  tactile  irritability.  We  must  assuun 
that  the  bacteria  multiplying  within  the  tissues  act  upon  the  amoeboio, 
cells  through  the  chemical  substances  which  they  produce,  sometimes  re 
pelting  or  paralyzing,  sometimes  attracting,  in  the  latter  case  affordin< 
conditions  favorable  for  phagocytosis.  The  bacterial  proteins  arisinj 
from  the  bodies  of  dead  or  dying  bacteria  and  j)assing  over  into  solutioi 
in  the  body  juices  have,  in  particular,  a  positive  chemotactic  action  upo 
the  phagocytes. 

The  result  of  the  taJcing-up  of  hacteria  into  cells  depends  in  a  particulai 
case  partly  upon  the  properties  of  the  devouring  cells,  partly  upon  th| 
properties  of  the  microparasites,  and  can  result  as  well  in  the  death  an; 
dissolution  of  the  parasite,  as  in  the  death  of  the  cells ;  or  in  a  symbiosi' 
of  the  cells  with  the  parasites,  the  latter  living  within  the  cells  urj 
changed  and  giving  rise  to  no  disturbance.  In  the  first-named  case  th! 
pliagocytosis  may  be  regarded  as  a  curative  j)rocess  which  hinders  ttj 
multiplication  and  spread  of  the  bacteria.  In  the  second  and  thirl 
cases,  on  the  contrary,  the  phenomenon  is  useless  for  the  prevention  (I 
the  spread  of  the  parasites;  indeed,  there  are  cases  (leprosy  and  to  soul 
extent  also  tuberculosis)  in  which  the  parasites  find  favorable  conditioij 
for  development  inside  of  the  cells,  increase  within  them,  and  final]; 
cause  their  destruction.  If  the  cells  containing  bacteria  remain  prl 
served  for  a  length  of  time,  they  may  wander  with  the  enclosed  bacterj 
to  other  parts  of  the  body,  in  this  way  effecting  a  metastasis.  j 

Phagocytosis  is  therefore  only  of  slight  significance  as  a  protective  force  \ 
a  certain  number  of  cases  ;  yet  it  cannot  be  doubted  that  the  phagocytes  i 
certain  infections  take  up,  not  only  dead  or  dying,  but  also  living  be! 
teria  not  yet  injured  by  other  agents,  and  can  cause  their  death.  Til 
collection  of  great  numbers  of  cells  in  the  infected  tissue  may,  throuf' 
the  close  pacMng  of  the  lymphatics,  offer  a  certain  mechanical  hindrance  j 
the  spread  of  bapteria,  yet  the  protection  so  afforded  is  frequently  ii 
sufficient.  j 

If  bacteria,  either  free  or  enclosed  in  cells,  pass  from  the  lymph-v(i 
sels  into  the  lymph=glands,  the  latter  act  as  filters,  as  in  the  case  I" 
dust,  and  retain  the  bacteria;  but  the  protection  which  they  offer;') 
Kutficient  only  when  the  bacteria  so  collected  in  the  lymph-glands  a|) 
liindered  in  their  reproduction  and  are  killed  by  the  influence  of  tb;* 
sunoundings.  The  destruction  may  be  accomplished  under  the  influer:; 
of  i)hagocytosis,  but  in  maiiy  cases  phagocytosis  is  possible  only  ivhenthe  br 
teria  arc  ircakrnrd  or  ha rr  already  been  killed.  Further,  the  taking-up 'f 
living  bacteria  by  the  cells  is  not  always  followed  by  destruction  of  tii 
baeteiia,  ])ut  there  very  frequently  takes  place  an  intracellular  multip- 
cation  of  the  bacteria.  ' 

More  important  than  phagocytosis  for  the  prevention  of  the  sprei 
of  bact<'ria  and  other  microparasites  is  the  influence  exerted  by  certii 
chemical  substances  in  solution  in  the  tissues.  Since  the  sapropl- 
tic,  nuii-]);itiiogeiiic  l)acteiia,  when  injected  into  living  tissue,  are  kill 


PKOTECTION    AGAINST    INFECTION.  103 

within  a  very  short  time,  we  must  assume  that /«  the  fismrs  ffirrc  arc 
present  chemically  active  substances  which  arc  poisonous  for  manji  bacteria  and 
can  cause  their  rapid  destruction.  Furlhei-,  since  many  iialliom'iiic  hac- 
teria  ordinarily  increase  only  locally  (tt'tanus-hacilli,  (liplilhcria-hacilli, 
cholera-spirilla)  and  after  a  certain  time  ])erish  within  the  inlccled  area, 
without  spreading-  further  through  the  body,  it  is  Aciy  pi-ohahle  tiiat  the 
tis,sues  of  the  bodi/  also  contain  substances  which  are  poisonous  for 
many  pathogenic  bacteria  and  prevent  their  spread.  Tlu^  phenomena 
observed  in  local  infections  speak  also  for  the  faet  tliat  such  substances 
at  times  are  formed  in  increased  amounts  or  are  aided  in  their  action  by 
uewly-formed  poisonous  substances.  It  is,  furthermoie,  probable  that 
the  crowding  of  cells  which  takes  place  in  the  infected  tissue  or  in  its 
ueighborhood  leads  also  to  an  inci'case  in  the])roduction  of  these  poison- 
ous sul)stances,  and  may  therel)y  hinder  the  spread  of  the  bacteria  ;  nev- 
ertheless, attention  should  be  drawn  to  the  fact  that  in  many  infections 
the  spread  of  bacteria  through  the  tissues  comes  to  a  standstill  in  places 
where  there  has  been  no  crowding  together  of  cells.  It  is  also  a  fact 
that  in  many  infections  the  spread  of  bacteria  through  the  body  by 
metastasis  is  either  wholly  wanting  (tetanus,  diphtheria)  or  at  least  is 
insigniticant  in  comparison  with  the  local  infection,  and  is  usually  fol- 
lowed by  relatively  insignificant  local  changes.  The  explanation  of  this 
fact  is  to  be  sought,  not  so  much  in  the  assumption  that  local  tissue- 
changes,  throngh  the  formation  of  special  chemical  substances  or  through 
the  aid  of  mechanical  substances  or  through  the  aid  of  mechanical  hin- 
drances— such  as  that  afforded  by  a  wall  of  cells — hinder  the  entrance  of 
bacteria  into  the  lymph  and  blood,  but  much  more  in  the  fact  that  there 
are  2»'^sent  in  the  lymph  and  blood  itself  certain  forces  which  are  able  to  in- 
jure and  weal-en  the  bacteria  taken  uj)  into  these  fluids  or  to  destroy 
them.     (See  ]»aragraph  l»elow  on  opsonins.) 

The  hostile  action  of  the  blood  on  bacteria  has  been  ascribed  to  the 
phagocytic  action  of  the  leucocytes;  and  this  theory  is  supported  by  the 
fact  that  such  a  phagocytosis  can  be  demonstrated  very  frequently  in 
acquired  infectious  or  after  the  artificial  introduction  of  bacteria  into  the 
blood ;  and,  further,  by  the  fact  that  the  bacteria  within  the  blood,  en- 
closed in  cells,  may  often  be  carried  out  of  the  blood-vessels  and  deposited 
in  different  organs — for  example,  the  spleen,  liver,  bone-marrow,  and 
the  kidneys — and  there  destroyed  or  excreted  from  the  body.  These 
observations  do  not  warrant  the  conclusion  that  phagocytosis  forms  a 
protection  against  the  spread  of  bacteria  in  the  lymi^h  and  l)lood ;  in- 
deed, in  those  very  cases  in  which  a  transportation  of  bacteria  tlir(>ugh 
the  blood  does  not  take  place,  phagocytosis  is  also  absent  ;  Mhile  on  the 
contrary,  the  entrance  of  bacteria  into  the  blood,  and  the  multiplication 
of  the  same  inside  of  the  blood-vessels,  is  very  often  accompanied  or  fol- 
lowed by  phagocytosis.  Here,  again,  phagocytosis  is  of  the  nature  of  a 
secondary  phenomenon  which  occurs  when  there  are  present  in  the  blood 
bacteria  or  piotozoa,  tliat  areiuit  able  to  i^revent  themselves  being  taken 
up  into  the  l)odies  of  the  leucocytes — that  is,  they  exert  a  i)ositive  at- 
traction on  the  i)hagocytes. 

When  bacteria  are  taken  up  by  cells,  they  either  di(^  or  coutinne  to 
multiply  inside  of  the  cells,  according  to  their  proi)erties  and  their  con- 
dition at  the  time  of  the  phagocytosis. 

The  forces  which  are  able  to  hinder  the  development  of  bacteria  in 
thebloodare  believed  l)y  the  majoiity  of  writ«'is  to  depend  upon  the 
presence  of  antibacterial  chemical  substances,  which  are  designated 


104  THE    PROTECTIVE    POWERS    OF   THE    BODY. 

alexins  (Buclnier)  or  myrosozins  (Hankiu),  According  to  Buclmer,  withij 
whom  the  majority  of  authors  are  in  harmony,  there  is  formed  a  fer- 
ment-like body,  an  enzyme  {cutase  [Metschnikoff]  ),  which,  through  the 
aid  of  an  intermediate  body  (amboceptor),  exerts  its  destructive  action 
upon  the  bacteria.  TJie  leucocytes  themselves  are prohably  the  ch  ief  producers 
of  this  protective  hodji,  and  the  leucocytosis  observed  in  the  bk:>od  in  the  Ml? 
couis('  of  many  infectious  may  therefore  increase  the  protective  powerf(*t«li 
(see  opsonins  below). 

So  far  as  conclusions  can  be  drawn  from  the  behavior  of  the  human 
and  animal  organisms  in  infectious  diseases,  we  may  assume  that  in  the 
blood  of  man  there  are  always  present  protective  chemical  substances,  that  is, 
alexins,  particularly  so  against  bacteria  which  uever  or  only  exception- 
ally enter  the  blood;  and  that  others,  on  the  contrary,  are  produced  only , 
during  the  course  of  an  infection,  so  that  not  until  a  certain  stage  of  the 
infection  does  an  inhibition  of  the  development  of  the  bacteria,  through 
the  formation  of   antibacterial    substances,    occur.     In   favor  of   such ; 
hypothesis  speaks  the  fact  that  many  bacteria  (typhoid-bacilli,  cholera- 
spirilla,  pus-cocci)  possess  at  first  their  full  virulence  when  distributed  \ 
through  the  body  by  the  blood,  but  later  suffer  a  loss  of  virulence  and 
finally  die. 

The  means  of  protection  which  the  organism  possesses  against  the  1 
poisons  produced  in  the  tissues  by  bacteria  are  to  be  found,  first,  in 
the  i)ussil)ility  of  a  rapid  excretion  of  the  poisons  by  the  kidneys,  or, 
under  certain  circumstances,  also  by  the  stomach,  intestine,  and  skin ; 
and  this  action  may  in  certain  cases  suffice  to  prevent  a  fatal  poisoning. 
Further,  in  certain  infections  in  which  true  toxins  are  formed  there  is  an 
antagonistic  action  on  the  part  of  the  organism,  in  the  sense  that  these 
poisons  are  made  ineffective  through  the  action  of  counter  poisons,  the  ; 
so-called  antitoxins.     (See  §  31  and  §32.)  ! 

The  antibacterial  properties  of  the  blood  and  lymph  against  certain  bacteria  have  been  • 
demonstrated    conclusively   by   the   experimental    investigations   of   various   writers.  '■ 
These  experiments  have  sho-mi  that  the  bactericidal  action  of  the  blood  of  a  given  ani- 
mal is  exerted  only  upon  certain  forms  of  bacteria  and  never  upon  all;    and  that  this  i 
action  is  subject  to  individual  variations.  | 

According  to  the  investigations  of  Fodor,  Petruschky,  Nuttal,  Ogata,  Buchner,  Beh-  \. 
ring,  Nissen,  Pansini,  and  others,  the  blood  and  the  serum  from  dogs,  rabbits,  and  • 
white  rats  are  capable  of  rendering  the  anthrax-l)acillus  harmless,  and  even  of  killing  it;  i 
but  this  action  is  a  limited  one,  so  that  after  the  introduction  of  a  large  number  of  the  i 
bacilli  into  the  blood  taken  from  the  vessels,  the  bacilli  after  a  time  begin  to  multiply,  i 
Defibrinated  blood  of  dogs  and  rabbits  can  destroy  the  cholera-spirillum  and  typhoid-  ' 
fever  bacillus;  but,  on  the  other  hand,  has  no  effect  upon  the  different  pus-cocci,  and  ' 
against  proteus;  the  same  is  true  also  with  regard  to  the  blood-serum.  Human  blood 
or  blood-.serum  can  kill  typhoid-bacilli,  diphtheria-bacilli,  and  the  bacilli  of  glanders. 

Von  Baumgarten  and  Walz,  as  well  as  A.  Fischer,  oppose  the  view  that  there  are 
chemically  active  substances  in  the  blood,  and  explain  the  natural  immunity  of  the 
tissues  and  the  blood  against  certain  bacteria  as  due  wholly  to  the  inability  of  the  bac- 
teria to  find  there  the  necessary  chemical  conditions  for  growth  and  multiplication. 
They  regard  the  fact  that  different  bacteria  which  have  been  passed  into  tlie  lilood 
or  l)lood-serum  do  not  develop  at  all,  or  show  but  partial  or  delayed  growth  and  a  great 
diminution  in  numbers  when  cultivated  upon  plates,  as  in  no  manner  speaking  for  the  ■ 
presence  of  l)actcricidal  substances  in  the  blood.     According  to  their  view,  the  second  j 
transplantation  into  another  culture-medium  causes  a  distvirbance  of  the  processes  ' 
of  assimilation  and  osmosis.     There  arise  in  consequence  plasmolytic  changes  in  the 
bacteria  present  in  the  serum;    during  the  pouring  of  the  plates  the  already  injured  < 
cells  die  from  dist\irbancos  of  assimilation.     On  the  other  hand,  it  is  to  be  noted  that 
A.  and  //.  Kossel  have  demonstrated  that  certain  products  of  animal  cells  (nucleinic 
acid,  protamine)  possess  l),ictcricidal  properties. 

The  alexins    of  tiic  IjJood  serum  are  made  inactive  through  heating  to  55°  C, 
and  are  very  susceptible  to  the  action  of   simlight  {Buchner),  and    they  can  also  be 


V 


BArTERTCTDAL    SUBSTAXCFS:     OPSONINS.  105 

destroyed  by  living  bacteria  and  their  deconiixisition  products.  They  resist  pepsin. 
The  addition  of  salt  to  the  serum  lowers  their  sensibility  to  heat.  By' means  of  a  90- 
per-cent  sodium  sulphate  solution  there  niaj-  be  obtained  from  ilog  serum  a  precipitate 
which  remains  active  when  dried  at  70°  C. 

The  bactericidal  action  finds  its  analogy  in  the  globulicidal  and  hsemolytlc 
action  of  the  serum;  that  is,  its  capacity  to  destroy  antl  dissolve  the  red  blood-cells 
of  an  animal  of  a  different  speci-s. 

According  to  the  investigations  of  Ehrlich  and  his  students  the  bactericidal  and 
);lobullcidal  antibodies  contain  two  components,  one  thermolabilc.  which  is  destroyed 
in'  heating  to  5")-()0  ('..and  a  thermostabilc,  which  resists  heating.  Hoth  nnist  act  to- 
gether in  order  to  bring  about  the  death  of  bacteria  or  the  dissolution  of  the  red  blood- 
cells. 

Ehrlich  designates  the  thermostabilc  component  as  the  immune  body  or  inter- 
mediate body  {Bordet  "as  the  substance  sensibilatrice  ").  the  thermolabilc  as  the  com- 
plement (earlier  designated  the  addiment).  To  the  immune  body  he  ascribes  two 
hapt')phorous  side-chains,  one  the  cytophile,  which  unites  with  the  cell  (bacterial  cell, 
red  blood-cell),  for  which  it  possesses  a  chemical  affinity,  and  a  complementopliilc,  which 
comiiines  with  the  complement.  It  is  therefore  an  amboceptor,  which  carries  over  the 
action  of  the  complement  to  the  cell.  Buchner's  alexin  is  identical  with  the  thermola- 
bile  component,  the  complement  of  Ehrlich  (Bordet).  That  a  union  of  the  immune 
body  with  red  blood-cells  and  bacteria,  respectively,  does  take  place  has  been  demon- 
strated by  the  investigations  of  Ehrlich,  Morgenroth,  Hahn,  Trommsdorff,  von  Dungern, 
and  others. 

Hankin,  Kanthack,  Denys,  Hahn,  Lowit,  and  others  assume,  on  the  ground  of 
experimental  investigations,  that  the  alexins  are  produced  by  the  leucocytes.  Kossel 
holdt  it  as  possible  that  the  nucleinic  acid  present  in  the  leucocytes  in  relatively  rich 
amounts  plays  a  role  in  the  destruction  of  the  bacteria.  Noesske  believes  that  the  eosino- 
phile  cells  of  the  bone-marrow  in  particular  produce  bactericidal  substances.     It  is  not 

I   possible  at  the  present  time  to  draw  a  definite  conclusion  as  to  the  part  played  by  the 

}   colorless  cells  of  the  blood  in  the  defence  against  infections. 

I  According  to  Bitter,  the  bactericidal  substance  fou)id  in  organs — that  derived  from 

the  lymph-glands,  spleen,  and  thymus — is  to  a  certain  extent  different  from  that  of  the 
blood  and  the  l)lood-serum,  and  therefore  does  not  originate  wholly  in  the  blood.     It  is 

:   certain  tliat  the  bactericidal  action  of  the  blood  is  not  the  only  protective  influence 

i   which  can  oppose  the  spread  of  an  infection,  or  wholly  prevent  it,  and  confer  immunity. 

I  According  to  observations  of  Czaplewski,  anthrax-bacilli  in  an  infected  organism, 

•  which  have  been  taken  up  into  leucocytes,  degenerate  as  a  rule  more  slowly  than  those 
lying  free  in  the  blood  and  tissue-juices.  It  appears,  therefore,  as  if  under  certain 
contlitions  the  cells  afford  to  the  bacteria  which  they  enclose  a  certain  degree  of  pro- 

1  tection  from  the  bactericidal  substances  of  the  tissue-fluids. 

!  The  antitoxins  which  render  the  bacterial  poisons  harmless  are  usually  formed  first 

I  during  the  course  of  the  infection;  but,  according  to  the  investigations  of  Wasser- 
\  mann,  Abel,  Fischl,  von  Wunschheim,  and  others,  the  serum  of  healthy  men  also  con- 
:  tains  such  substances.  Serum  which  contains  the  antitoxin  against  a  certain  toxin — 
as,  Tor  example,  that  against  the  diphtheria-toxin — can  be  a  good  culture-medium  for 
'  the  given  bacteria;   the  antitoxin  does  not  destroy  the  bacteria. 

Animals  refractory  toward  diphtheria  contain  in  the  blood  serum  no  diphtheria 

;  antitoxin,  but  accordhig  to  Wassermann  about  80  per  cent  of  human  individuals  have 

in  their  blood  a  not  insignificant  amoimt  of  antitoxin.     The  immunity  of  the  animals 

depends  therefore  not  upon  the  presence  of  the  antitoxin,  but  on  a  lack  of  affinity 

between  the  poison  and  the  tissue-cells    {Ehrlich  and  Wassermann).      It    is   possible 

I  to  produce  in  mice  a  fatal  intoxication  with  the  blood  of  apparently  healthy   fowls 

j  that  have  been  injected  with  large  doses  of  tetanus  toxin. 

Opsonins.     The  protective  function  of  phagocytosis  has  in  recent  years  been 

accorded  a  po,sition  of  great  importance  through  the  discovery  by  Wright  and  Douglas 

(1902)  of  the  presence  in  the  blood  and  other  fluids  of  the  body  of  certain  sulistances, 

'  called  by  them  opsonins,  which  render  various  bacteria  susceptible  to  the  phagocytic 

'  action  of  leucocytes.     It  is  now  apparently  an  established  fact  that  certain  special 

•  .substances,  normal  and  immune,  act  upon  the  bacteria  ant!  change  them  in  such  a 
manner  that  they  are  readily  taken  up  by  polynuclear  leucocytes  in  vitro.  Op.so- 
nins  capable  of  acting  upon  a  varietj^  of  l)acteria  occur  in  normal  blood.  They  appear 
to  be  the  mo.st  important  antibodies  in  infections  with  stref)tococci,  staphylococci, 
pneumococci,  micrococcus  melitensis,  gonococci,  meningococci,  the  bacilli  of  plague, 
dysentery,  anthrax,  tuberculosis,  typhoid  fever,  the  colon  bacillus,  cholera  spirillum, 
etc.     Whether  this  wide  range  of  opsonic  action  is  dependent  upon  a  common  o])sonin 

;  or  upon  a  variety  of  specific  opsonins  is  not  yet  determined.     Si)ecificity  of  the  opsonins 
;  probably  does  not  exist.     Various  researches  suggest  that  they  may  be  a  constant 


100  THK    PROTECTIVE    POWERS    OF   THE    BODY. 

quantity.  They  are  to  a  certain  extent  thermolabile,  being  partly  destroyed  at  60-65' 
C.  Bacteria  first  treated  with  normal  serum  and  then  exposed  to  this  temperature: 
are  taken  up  as  under  normal  conditions.  The  opsonic  power  of  the  blood  is  increased: 
in  recovery  from  infection,  and  it  can  also  be  artificially  increased  by  immunization 
with  living  attenuated  bacteria,  dead  bacteria,  or  proteid  constituents  of  the  bacterial- 
cells.  The  opsonic  index  is  the  relative  influence  of  a  patient's  blood  upon  phagocy-^ 
tor.is  as  compared  with  that  of  normal  individuals.  It  is  determined  by  mixing  in 
a  capillary  tube  equal  parts  of  the  patient's  serum,  a  suspension  of  leucocytes,  and  an. 
emulsion  of  the  bacteria  against  which  the  index  is  taken.  Control  tests  are  made  in! 
the  same  way  with  normal  serum.  The  mixtures  are  incubated  for  a  time,  thin  smears 
are  made,  dried,  and  stained,  and  the  average  number  of  bacteria  taken  up  by  the 
leucocytes  is  estimated.  Regarding  the  index  of  the  normal  blood  as  unity,  the  average 
number  of  bacteria  in  the  leucocytes  of  the  patient's  serum  divided  by  it  will  be  the; 
opsonic  index.  75-100  leucocytes  are  usually  counted.  A  low  opsonic  index  is  taken- 
as  indicating  the  presence  of  an  infection  or  of  a  low  degree  of  resistance  to  it,  while  a' 
high  index  indicates  a  high  degree  of  resistance  to  a  recovery  from  infection. 

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Ziegler,  viii.,  1890. 
Petruschky:   Der  Verlauf  der  Phagocytencontro verse.  Fortschr.  d.  Med.,  viii.,  1890; 

Einwirkung  des  lebenden  Froschkorpers  auf  den  Milzbrandbacillus.     Zeit.  f.  Hyg., 

vii..  1889. 
Podwyssozki :   Die  Reservekrafte  des  Organismus,  Jena,  1894. 
Sanarelli:   Die  L'rsachen  der  natiirl.  Immunitat  gegen  Milzbrand.     Zeit.  f.  Bakt.,  ix., 

1891;    Defense  de  I'organisme  contre  les  microbes.     Ann.  de  I'lnst.  Pasteur,  vii., 

1893. 
Stem:   Ueber  die  Wirkung  des  menschlichen  Blutes  und  anderer  Korperfliissigkeiten 

auf   pathogene   Mikroorganismen.     Zeit.    f.    klin.   Med.,    18   Bd.,    1890;     Neuere 

Ergebnisse  auf  dem  Gebiete  der  Immimitatslehre.     Cbl.  f.  allg.  Path.,  v.,  1894 

(Literaturubersicht). 
Strasburger:  Die  Bedeutung  d.  normalen  Darmbakterien.  Mfmchen.  med.  Woch., 

1903. 
Walz:   Baktericide  Eigenschaften  des  Blutes,  Braunschweig,  1899. 
Wassermann :  Personl.  Disposition  gegen  Diphtherie.    Zeitschr.  f.  Hyg.,  xix.,  1895. 
Werigo:  Les  globules  blancs  comme  protecteurs  du  sang.     Ann.  de  I'lnst.  Pasteur, 

vii.,  1893;   Developp.  du  charbon  chez  le  lapin.     lb.,  viii.,  1894. 
Wyssokowitsch:  Schicksal  der  ins  Blut  injic.  Mikroorganismen.     Zeitschr.  f.  Hyg., 

i.,  1886. 
Ziegler:   Ursachen  und  Wesen  der  Immunitat  des  menschlichen  Organismus  gegen  In- 

fectionskrankheiten.     Beitr.  v.  Ziegler,  v.,  1889;    Schutzkrafte  des  menschlichen 

Organismus.   Akad.  Rede,  Freiburg,  1892;  Die  Lehre  von  der  Entzundung.   Beitr. 

V.  Ziegler,  xii.,  1892. 
See  also  Literature  to  ^^  31  and  32. 

(Opmrnus.) 

Barratt:  Proc.  Roy.  Soc,  1905. 

Bulloch:  Lancet,  1905;    Practitioner,  1905. 

Cole  and  Meakins:  Johns  Hop.  Ho.sp.  Bull.,  1907. 

Cowie  anil  Chapin:    Jour,  of  Med.  Res.,  1907. 

Dean:    Proc.  Hov.  Soc,  1905. 

Hamilton:   Jour,  of  Infect.  Dis.,  1907. 

Hamilton  and  Horton:  Ibid.,  1906. 

Hektoen:  Jour  Ainer.  Med.  A.ss.,  1906;  Jour,  of  Infect.  Dis.,  1906,  1907. 

Horton:  Jour,  of  Infect.  Dis.,  1906. 


I 

ll 

108  THE    PROTECTIVE    POWERS    OF   THE    BODY. 

Jeans  aiul  Sellards:  Johns  Hop.  Hosp.  Bull.,  1907. 
Klien:  Ihid. 

Lawson  and  Stewart:  Lancet,  1905. 
Moss:   Johns  Hop.  Hosp.  Bull.,  1907. 
Rosenow:   Join-,  of  Infect.  Dis.,  1907. 
Rotch  and  Floyd:  J.  Amer.  Med.  Ass..  1907. 
Ruedig-er:  J.  Amer.  Med.  Ass.,  1905,  1906. 
Russell:  Jour.  Inf.  Dis..  1907. 
Sin-xon:   Jour,  of  Exp.  Med.,  1906. 
Tunnicliff:   Jour,  of  Infect.  Dis.,  1907. 
Walker:  Join-.  Med.  Res.,  1907. 

Wright:  Med.  Chir.  Trans.,  1905;   Lancet,  1905;   Jour.  Amer.  Med.  Ass.,  1907;    Prac- 
titioner, 190S. 
Wright  and  Douglas:   Proc.  Roy    Soc,  1903,  1904;    Lancet,  1904. 

§  31.  The  healing=powers  of  the  human  body  are  furnished  by  those 
life-processes  ichich  are  able  to  compensate  for  the  disturbances  and  changes 
caused  by  disease,  and  to  render  harmless  or  to  remove  any  harmful  agent  that 
may  still  be  present  in  the  body.  If  portions  of  tissue  have  been  destroyed,  the 
healing  consists  essentially  in  the  removal  of  the  changed  and  dead  tissue,  and 
its  replacement  by  new  tissue.  ; 

When  from  any  cause  the  temperature  of  the  body  becomes  abuor-  ■ 
mally  low  or  abnormally  high,  compensation  may  be  effected  in  such  i 
a  way  that  through  the  suitable  regulation  of  the  heat-production  and  } 
heat-dispersion  the  temperature  of  the  body  may  be  brought  back  , 
to  the  normal.  If  through  trauma  a  portion  of  tissue  is  destroyed,  the  \ 
organism  may  repair  the  defect  either  through  the  local  production  of 
new  tissue  {regeneration)  or  by  a  corresponding  increase  in  other  similar  '; 
tissues  {compensatory  hypertrophy).  \ 

If  poisons  enter  the  body  and  produce  symptoms  of  intoxication,   \ 
healing  can  follow  only  through  the  rapid  excretion  of  the  poison,  or  its  ' 
destruction  or  neutralization  within  the  body ;  while  at  the  same  time  the 
damaged  tissues,  under  the  influence  of  normal  nutrition,  again  return  : 
to  their  normal  state,  existing  defects  being  properly  compensated.  [ 

In  infections  the  healing  processes  follow  directly  ui)on  the  aeiion  of  \ 
the  protective  forces  ;  indeed,  the  action  of  the  latter  constitutes  the  first  ; 
stage  of  healing;  the  protective  and  healing  processes  are  in  paH  identical. 

In  many  infectious  diseases  the  healing  influence  of  protective  sub-  ; 
stances  already  present  in  the  affected  body  is  supplemented  by  the  ap= 
pearance  of  new  substances  foreign  to  the  normal  organism,  which  as 
bactericidal  substances  and  as  antitoxins  antagonize  both  the  infection  i 
and  the  intoxication.     The  bactericidal  antibodies  are  formed  by  the  ( 
tissue-cells  which  through  the  infection  have  been  placed  under  altered  i 
conditions  of  life;  they  spread    throughout  the  tissue- juices,  and  thus  ; 
hinder  the  further  extension  and  multiplication  of  the  bacteria.     They 
are  formed  particularly  in  typhoid  fever,  cholera,  and  plague,  and  show 
constantly  a  certain  sjyecificity  in  that  they  influence  primarily  those  bacteria 
through  whose  vital  activities  they  have  arisen.     This  specificity  is,  how- 
ever, not  al)sohitc,  inasmuch  as  they  can  act  upon  closely  related  species. 

Antitoxins  ar(i  formed  in  those  infections  in  which  toxins  are  pro- 
duced. The  action  of  tlie  toxin  takes  place  in  this  manner  (Ehrlicli) : 
the  poison  molecule  combines  through  a  hajitophorous  side-chain  with 
the  Jiai)tophoi"()us  group  of  certain  cells,  while  the  toxophorons  side- 
chain  of  the  poison  exerts  its  influence  in  a  specific  manner  upon  the 
affected  cells,  so  that  we  may  regard  the  antitoxins  as  representing  noth- 
ing moi-e  than  an  excess  of  haptophorous  side-chains  of  the  cell-substance  sus- 


antitoxins:     specific    bactericidal    SlHSTANCnCS.         100 

ceptible  to  the  imison,  that  are  given  off  into  the  J>Jood-sernm  and  into  the  bod;/- 
jnieea,  and  eonit)ine  the  eorrespondin;/  haptophoronn  ,side-ehains  of  the  toxin. 
The  luiptopborous  oronp  of  the  toxin  is  tluMoby  prt'x ciitod  from  carryinfj 
over  its  (oxt>[)liorous  tiroup  to  the  ceils  and  tlicrchy  1  )<'(•( )inin<;-  active. 
Toxin  and  autitoxiu  combine  according  to  iixed  quantitative  relations. 

Antitoxins  are  formed  against  the  poison  of  diphtheria  and  tetanus,  the  pyo- 
cyaneus  poison,  ricin.  snake-poison,  the  poison  of  eel-blood,  and  certain  mushroom 
poisons. 

Since  the  antitoxins  of  snake-venom  {Cahnctte)  and  that  of  the  pyocyaneus  toxin 
OVasscrmunn)  are  more  easily  destroyed  than  the  poisons  themselves,  it  is  |)i)ssil)le  in  a 
mixture  of  the  two.  when  the  combination  has  lasted  but  a  sliort  tinu>,  to  destiny  jyy 
heating  to  a  certain  degree  the  antitoxin  alone,  so  that  the  toxin  again  becomes  .letive. 
The  virulence  of  the  toxin  of  diphtheria  is  weakened  with  age,  through  the  fact 
that  the  toxophorous  group  in  jsart  becomes  inactive. 

If  the  favoral:ile  course  and  the  healing  of  an  infectious  disease  depend  essentially 
upon  the  production  of  antitoxins,  the  bacteria  concerned  may  still  be  preserved  and 
increase  in  numbers;  only  the  harmful  action  is  averted.  After  a  certain  time  they  also 
die. 

According  to  investigations  by  R.  Pfclffcr,  confirmed  liy  Sobernheitn,  Dunbar, 
Loefflir.  and  otliers  there  is  found  in  the  blood-serum  of  animals  made  immune  against 
typhoid-bacilli  or  cholera-spirilla,  or  of  human  individuals  suffering  or  convalescing 
from  typhoid  fever  and  cholera,  a  specific  bactericidal  substance  (lysogimous 
substance  of  C.  Fraenkelj.  The  addition  of  such  a  serum  to  a  virulent  bouillon-culture 
of  these  bacteria  so  changes  the  latter  that  the  bacteria  when  inoculated  into  the 
peritoneal  ca\ity  of  an  experimental  animal  rapidly  disintegrate  into  little  spherules 
and  are  finally  dissolved. 

Bordet  has  sho\vn  that  a  fresh  human  serum  is  active  also  in  the  test-tube  outside 
of  the  human  body.  When  heated  to  56°  C.  this  activity  is  lost  (inactivation)  but  it 
may  be  restored  again  through  the  addition  of  normal  serum  (reactivation). 

According  to  the  investigations  of  Gruber,  Durham,  Pfeijfer,  Kolle,  Sobernheim, 
Widal,  C.  Fraenkel,  and  others,  the  blood-serum  of  individuals  ill,  convalescing,  or  en- 
tirely recovered  from  typhoid  or  cholera  exerts  a  damaging  influence  upon  typhoid- 
i  bacilli  or  cholera-spirilla  respectively;  this  influence  being  of  such  a  nature  that  in 
I  bouillon-cultures  the  bacteria  so  affected  become  motionless,  clump  together,  sink  to 
I  the  bottom  of  the  vessel,  and  are  destroyed.  When  the  serum  is  added  to  a  hanging 
I  drop  of  bouillon-culture,  the  rapidly  moving  vibrios  at  once  become  motionless  and 
I  collect  in  little  heaps.  Gruber  believes  that  this  phenomenon  is  to  be  explained  by  a 
i  swelling  and  bursting  of  the  membrane  of  the  bacterial  cell,  and  assumes  that  this 
I  change  enables  the  alexins  to  destroy  the  bacteria  present  in  the  body.  He  therefore 
I  designates  the  active  substances  in  the  serum  as  agglutinins,  and  believes  that  to  these 
;  may  be  attributed  the  chief  agency  in  the  healing  of  infectious  diseases  and  in  the  pro- 
;  duction  of  immunity  against  the  same.  Pfeiffer,  on  the  contrary,  denies  the  occurrence 
of  any  swelling  of  the  cell-membrane,  and  explains  the  phenomenon  as  due  to  an  in- 
hibition of  development,  and  designates  the  active  substances,  the  nature  of  which  is 
.  wholly  unknown,  as  specific  paralysins.  After  Gruber  had  demonstrated  the  peculiar 
I  action  of  the  blood-serum  of  typhoid-fever  patients,  Widal  (Sem.  mrdicale,  Paris,  1S96) 
i  proposed  that  this  action  of  the  blood-serum  on  cholera-spirilla  and  typhoid-l)acilli 
f  respectively  be  utilized  as  a  diagnostic  aid  during  the  course  of  an  attack  of  typhoid. 
I  Numerous  "clinical  investigations  have  demonstrated  that  it  is  possible,  during  tiie 
!  course  of  the  attack  or  for  a  long  time  (several  months)  afterward,  to  make  a  diag- 
;  nosis  of  typhoid  from  the  action  of  the  blood-serum  upon  cultures  of  typhoid  bacilli 
I     {Widal's  reaction).    (See  ^  3.3.) 

According  to  Kraus,  there  is  present  in  the  blood  of  animals  artificially  immunized 
against  cholera  and  typhoid  fever  a  body,  which,  on  the  addition  of  .such  a  serum  to  a 
clear  bacteria-free  filtrate  of  cultures  of  cholera  or  typhoid  bacilli,  produces  in  the 
latter  a  clouding  and  later  a  precipitation,  thus  acting  as  a  precipitin.      (See  ^  33.) 
'  The  protective  substances  which  uppciir  in  the  blood  in  the  course  of  infectious 

disea.ses  are  not  always  formed  at  the  same  place;  in  pneumonia  they  are  said  to  be 
produced  in  the  bone-marrow  {Wassermann);  in  cholera  and  typhoid  fever  in  the  spleen 
(Pfeiffer  and  Marx);  in  "  Rinderpest  "  in  the  liver  (Korh).  'Tluy  are  to  be  regarded 
as  s/wrf^/ic  .SYY7Y'/r-y/-y /y/w/7/r/.s- iirisiu-j;  in  response  to  specific  stimuli. 

The  bactericidal  iinmune=bodies  are,  according  to  their  phy.sical  and  chemical 
properties,  to  be  regarded  as  /"r/wrn/.s  (they are  neither  globulins  nor  albumins).  1  he 
immune-bodies  combined  with  the  bacterial  cells  during  bacteriolysis  may  be  set  free 
after  the  solution  of  the  bacterial  protoplasm,  and  again  become  capable  of  action. 


110  THE    PROTECTIVE    POWERS    OF    THE    BODY. 


1 


It  has  often  been  assumed  that  the  fever  occurring  in  infectious  diseases  is  a  pro- 
tective process  favoring  the  destruction  of  bacteria;  and  it  is  not  impossible  that  in 
individual  cases  it  may  exert  such  a  favorable  influence.  Thus,  for  example,  it  is  con- 
ceivable that  a  parasitic  micro-organism,  growing  well  at  a  temperature  of  37-38°  C, 
will  not  thrive  at  a  temperature  of  40-41°  C,  so  that  high-fever  temperatures  may  hin-j 
der  its  power  of  reproduction.  The  conclusion  should  not,  however,  be  drawn  from  ' 
this  that  fever  is  a  useful  phenomenon  which  always  favors  the  counterbalancing  of 
pathological  disturbances.  Even  in  those  cases  in  which  the  metabolic  processes  occur- 
ring during  the  fever  exert  an  injurious  influence  upon  the  bacteria,  this  is  not  to  be 
taken  as  proving  the  usefulness  of  fever.  We  can  only  say  that  a  part  of  the  morbid 
processes  occurring  during  an  infectious  fever  leads  to  a  formation  of  decomposition- 
products  which  may  possess  antibacterial  or  antitoxic  properties. 

Literature. 

{Bactericidal  Substances  and  Antitoxins.) 

Banti:   Sulla  distruzzione  dei  batteri  nell'  organismo.     Arch.  p.  le  Sc.  Med.,  xiii.,  1889.;  -i 
Biedl  u.  Kraus:  Ausscheidung  d.  Mikroorganismen  durch  Drusen.     Zeit.   f.    Hyg.Jr 

xxvi.,  1897. 
Bitter:   Metschnikoff's  Phagocytenlehre.     Zeit.  f.  Hyg.,   iv.,    1888;    Bakterienfeindl.l 

Stoffe  thier.  Organe,  ib.,  xii.,  1892.  I 

Bordet :  Action  des  serums  preventifs.     Ann.  de  ITnst.  Past.,  1896;  Mecanisme  de  I'ag-j 

glutination,  ib.,  1899.  II 

Bordet  et  Genon:  Substances  sensibilatrices  des  serums  antimicrobiens.     A.  d.  ITnst. 

Past.,  1901. 
Bouchard:   Les  microbes  pathogenes,  Paris,  1892. 
Brieger:   Antitoxine  und  Toxine.     Zeit.  f.  Hyg.,  xxi.,  1896. 

Conradi:  Bildung  baktericider  Stoffe  bei  der  Autolyse.     B.  v.  Hofmeister,  i.,  1901. 
Deny s  et  Havel:  La  part  des  leucocytes  dans  le  pouvoir  bactericide   du   sang.     La 

Cellule,  X.,  1893.  ] 

Durham:   On  a  Special  Action  of  the  Serum.     Journ.  of  Path.,  iv.,  1896. 
Eichel:   Wachsthumsverhaltnisse  verschied.  Bakterien  im  Fieber.     Virch.  Arch.,  121 

B(l.,  1890. 
Foerster:   Die  Serodiagnostik  d.  Abdominaltyphus.     Fortschr.  d.  Med..    1897  (Sam- 

melref.). 
Fraenkel,  C;    Agglutinine  bei  Typhus  abdom.    (Widal'sche    Probe.)      Deut.  med.'    ;  a\ 

Woch.,  1897  (Lit.). 
Gamaleia:  Destruction  des  microbes  dans  les  organismes  febricitants.     Ann.  de  ITnst. 

Past.,  1883.  '. 

Golgi:   II  fagocitismo  neir  infezione  malarica.     Arch.  ital.  de  Biol., xi.,  1889. 
Gruber:    Immunitat  geg.  Cholera  u.  Typhus.     Wien.  med.  Woch.,  1896;   Theorie  dei; 

Immun.  (Agglutinine).     Miinch.  med.  Woch.,  1897;    Serumdiagnostik  d.  Typhus. 

ib.;   Theorie  der  Agglutination,  ib.,  1899. 
Hahn:  Bezieh.  d.  Leukocyten  z.  baktericiden  Wirkung  d.  Blutes.     Arch.  f.  Hyg.,  25 

Bd.,  1895. 
Jetter:   Buktericide  Eigensch.  d.  Blutserums.     Arb.  a.  d.  path.  Inst,  zu  Tubingen, 

1893. 
Loewy  u.  Richter:   Heilkraft  des  Fiebers.     Virch.  Arch.,  145  Bd.,  1896  (Lit.). 
V.  Klecki:  Ausscheidung  d.  Bakt.  durch  d.  Nieren.     Arch.  f.  exp.  Path.,  39  Bd., 

(Lit.). 
Melnikow:  Bedeutung  der  Milz  bei  Infectionen.     Zeit.  f.  Hyg.,  xxi.,  1896  (Lit.). 
du  Mesnil:  GrulK^r-Widal'sche  Sprumdiagnostik.     Miinch.  med.  Woch.,  1897. 
Nissen:  Bakterionvernichtende  Eigenschaften  des  Blutes.     Cbl.  f.  Bakt.,  iv.,  1889. 
Oppenheimer:  Toxine  imd  Antitoxine,  Jena,  1904. 
Pawlowsky:   Ileilung  des  Milzbrandes  durch  Bakterien  u.  das  Verhalten  der  Milz- 

lir:iiidl)acillen   im   Organismus.     Virch.   Arch.,    108   Bd.,    1887;    Bemerk.   lib.  d 

Mittheilung  v.  lunmerich  u.  di  Mattel:   Ueber  Vernichtung  der  MilzbrandbacUlen 

im  Organisnuis.     Fortschr.  d.  Med.,  vi.;    Infection  u.  Immunitat.     Zeit.  f.  Hyg. 

33  Bd.,  1900. 
Pernice  u.  Scagliosi:   Ausscheidung  d.  Bakt.  a.  d.  Organismus.     Deut.  med.  Woch. 

1X92  (Lit.). 
Pfeiflfer  (Kolle,  Vagedes):  Ein  neues  Grundgesetz  d.  Immunitat,  etc.     Deut.  med 

Woch..  1896;   Specifische  Immunitatsreaction  der  Typhusbacillen,     Zeit.  f.  Hyg. 

xxi.,  1896  (Lit.);    Weitere  Untersuchungeu  lib.  specifische  Immunitatsreaction 


niMrxiTY.  1 1 1 

Cbl.  f.  Bakt.,  XX..  1896  (Lit.);    Wirkimg    und  .\rt.  d.  aktiven    Substanz  d.  pni- 

ventivon  u.  toxischen  Sera.     Ibid.,  xxxv.,  1!)04. 
Roger:   Elimination  des  poisons.     Path.  s^n.  de  IJouchard,  i..  Paris,  bSy.^. 
Bufifer:    Dost  met.  des  microbes  par  les  cellules  amooboides.     Ann.  dcl'lnst.  Past.,  v., 

1S91. 
Sherrington:  Exper.  on  the  Escape  of  Bacteria  with  the  Secretions.     Journ.  of  Path., 

i..  189;}  (Lit.). 
Tsnboi:   Die  Schutz-  und  Heilsubstanz  des  Blutes,  Wiesbaden,  1892. 
Wassermann :  Pneumokokkenschutzstoffe.     Dout.  nied.  Woch.,  1899. 
"Williamson:   Leukocyten  hoi  Pnemnokokkeninfektion.     B.  v.  Ziepler,  xxix.,  1901. 
Widal  ct  Sicard:    Le'srrodiasnostic.     Ann.  de  I'Inst.  Past.,  1897  (Lit.). 
Ziegler:   Die  I'rsachen  d.  pathol.  Geweb.sneubildungen.     Internat.  Beitr.,  ii.,  Festr.  f. 

Virchow,  Berlin,  1891;  Ueb.  d.  Zweckmassigk.  d.  pathol.  Lebensvorgange.  Miincli. 

med.  Woch.,  1896. 
See  also  §  30,  §  32,  and  §  33. 

II.  The  Acquiring  of  Immunity  against  Infection  and  Intoxication. 
Protection  through  Inoculation. 

:?  32.  The  acquiring  of  immunity  against  a  particular  infectious 
disease  is  a  pheuomeuou  whose  frequent  occurrence  has  louj;-  been  known 
through  clinical  observations.  This  fact  has  been  established  chiefly  by 
the  observation  that  the  great  majority  of  men  suffer  but  one  attack  of 
such  widespread  infections  as  measles,  smallpox,  whooping-cough,  scar- 
let fever,  and  diphtheria,  and  that  after  such  attack  they  are  spared  by 
the  disease,  even  when  they  expose  themselves  under  the  most  varied 
conditions  to  the  danger  of  infection  with  its  poison.  The  knowledge  of 
this  fact  is  very  old,  and  early  in  the  eighteenth  century  it  had  led,  in 
the  Orient,  to  attempts  to  obtain  immunity  against  the  natural  contagion 
of  smallpox  by  the  inoculation  of  material  from  smallpox  pustules.  In 
the  latter  part  of  the  eighteenth  century  Jenner  discovered  that  the  dis- 
ease known  as  cowpox — i.e.,  a  milder  form  of  pox,  which  is  an  attenuated 
form  of  human  smallpox — afforded  protection  against  the  true  smallpox. 
As  a  result  of  this  observation,  since  the  beginning  of  the  year  1796,  at  first 
by  Jenner  himself,  afterward  by  the  physicians  of  all  civilized  countries, 
artificial  inoculations  of  cowpox  have  been  carried  out  upon  millions  of 
human  individuals,  with  the  result  that  through  such  inoculation  a  high 
degree  of  immunity  against  the  true  smallpox  has  been  secured  to  the 
inoculated;  so  that  at  the  present  time,  in  all  countries  where  vaccina- 
tion is  universally  practised,  the  occurrence  of  widespread  epidemics  of 
smallpox,  once  so  frequent,  is  very  rare,  and  the  disease  no  longer  as- 
I  sumes  the  character  of  a  dangerous  pestilence. 

;  The  investigations  of  the  last  decades  with  regard  to  the  causes  and 
origin  of  infectious  diseases,  which  have  covered  such  an  extiaordiiiai'ily 
broad  field,  have  shown  that  the  acquiring  of  immunity  against  a  cer- 
tain infectious  disease  through  one  attack  of  the  given  disease  oc- 
curs in  different  infectious  diseases,  especially  in  those  lumiing  an  acute 
course;  and  represents  sometimes  a  transitory,  at  other  times  a  per- 
manent peculiarity  of  the  individual  concerned,  which  in  i)regnant 
women  maybe  transmitted  to  the  fa'tus  m  utcro.  These  observations 
have  also  shown  that  the  single  or  repeated  inoculation  of  attenuated 
pathogenic  bacteria — that  is,  of  bacteria  which  on  account  of  their  sliglit- 
virulence  produce  a  disease  that,  in  contrast  to  the  natural  infection  with 
bacteria  of  full  virulence,  is  relatively  insignificant,  often  localized  to  a 
limited  area — can  also  confer  immunity  against  the  coii-esponding  dis- 
ease.    Further,  it  has  been  demonstrated  that  the  injection  of  certain 


112  THE    PROTECTIVE    POWERS    OF   THE    BODY. 

chemical   substances  produced  by  the  bacteria  is  siifficieut  to  confer 

imjiuinity  a.uaiiist  certain  infections. 

Immunity  through  the  inoculation  of  attenuated  specific  disease- 
germs  may  be  i)rodnced,  for  example,  against  anthrax,  symptomatic 
anthrax,  ehieken-cholera,  diphtlieria,  and  swine-erysipehis.  The  weak- 
ening of  the  virulence  of  bacteria  may  be  produced  either  by  the  action 
of  high  temperatures  or  chemical  agents,  or  by  the  action  of  the  air  alone ; 
further,  it  may  also  be  produced  by  the  inoculation  of  the  bacteria  into 
certain  animals  or  through  their  long-continued  cultivation  on  artificial 
media.  Inoculation  is,  in  general,  carried  out  by  injecting  subcutaue- 
ously  first  markedly  attenuated,  then  less  attenuated,  and  finally  fully 
virulent  bacteria  together  Avith  their  products. 

According  to  the  investigations  of  numerous  authors,  immunity  in 
animals  may  also  be  produced  by  the  injection  of  sterilized  cultures  iu 
which  the  bacteria  are  completely  killed — as,  for  example,  against  Ameri- 
can hog-cholera,  symptomatic  anthrax,  diphtheria,  the  infectious  disease 
produced  experimentally  in  rabbits  by  the  injection  of  the  Bacillus  pyo- ; 
cyaneus,  and  the  infection  produced  iu  guinea-pigs  by  cholera-spirilla,       ; 

A  third  form  of  artificial  immunization,  which  Eaynaud  attempted  aS' 
early  as  1877,  but  was  first  securely  established  by  Behring  in  1890,  can ; 
l)e  ])r(>duced  by  the  injection  into  man  or  an  exi^erimental  animal  of  j 
blood=serum  taken  from  animals  which  were  previously  susceptible,  ^ 
but  have  been  rendered  immune  by  means  of  inoculations.  The  most' 
extensive  and  at  the  same  time  the  most  successful  attempts  thus  far 
made  have  been  carried  out  with  diplithena  and  tetanus ;  that  is,  iu  dis- 
eases in  which  intoxication  through  toxins  forms  the  most  striking  fea- 
ture. Moreover,  successful  experiments  with  the  blood-serum  of  immu- 
nized animals,  in  the  case  of  cholera,  swine-erysipleas,  anthrax,  typhoid 
fever,  and  plague,  have  been  reported. 

The  specific  ])rotectiou  which  the  blood-serum  affords  may  be  secured, 
not  only  by  injection  before  infection  occurs,  but  also  after  infection 
^as  ali'cady  taken  place;  so  that  the  serum  may  be  designated  not  only  a 
protective  serum,  but  also  a  healing  serum.  For  both  protectior 
against  and  for  the  cure  of  a  certain  infection  a  definite  amount  of  serun. 
is  necessary,  the  precise  amount  depending,  on  one  hand,  upon  the  se ; 
verity  of  the  infection,  and  On  the  other,  upon  the  activity  of  the  serun^ 
itself,  which  increases  with  the  completeness  of  the  immunization  of  th(j 
originally  susceptible  animal  furnishing  the  serum.  If  the  serum  is  uoj 
injected  until  after  infection  has  occurred,  the  amount  of  serum  must  ht 
so  much  the  greater  the  longer  the  lapse  of  time  after  the  beginning  o 
the  infection. 

In  the  case  of  true  bacillary  diphtheria,  the  injection  of  curativi 
diphtheria-serum  has  now  been  carried  out  iu  thousands  of  cases,  o 
both  severe  and  light  forms;  and  there  is  without  any  doubt  a  beneficia, 
intbiciicc  exerted  upon  the  course  of  the  disease,  as  shown  by  a  rapi«; 
improvement  of  the  patient's  general  condition  (rapid  establishment  o' 
i'uphoria,  fall  of  fever,  improvement  in  the  pulse),  as  well  as  by  thi 
faxorable  course  pursued  by  the  local  disease.  In  tetanus  a  definite  cui| 
ative  action  of  serum  lias  been  demonstrated  iu  the  case  of  experiments 
animals,  guinea-])igs,  and  mice;  but  the  results  iu  man  have  not  yet  bee 
fully  determined. 

The  blood-serum  of  immunized  animals  exerts  its  beneficial  actioi' 
without  doubt,  through  the  presence  of  a  counter -poison,  an  antitoxir; 
which  neutralizes  the  poisons  produced  by  the  bacteria.     In  the  case  ci 


I 


IMMUNITY.  113 

the  patients  treated  by  a  given  antitoxin,  there  is  produced  a  poison- 
immunity  ajiiiinst  the  correspondinj;  bacterial  ])oison — as,  foi-  exaniph', 
aji'ainst  the  i)()is()u  proihieed  by  the  di])htlieria-ba('illi,  in  those  i)atieiits 
injected  with  diphtheria-antitoxin — and  this  immunity  is  to  be  ascribed 
to  the  presence  of  a  definite  amount  of  antitoxin  in  the  bU)od. 

Besides  the  antitoxins,  the  blood-sei-nm  of  immunized  animals  or 
human  beinus  may  also  contain  bactericidal  substances,  whicli  injure  or 
kill  the  bacteria  themselves;  and  this  is  said  to  occur  especially  in  cliolei'a 
and  typhoid  infections. 

In  the  case  of  immunization  by  means  of  attenuated  cultures  or  by 
steiilized  chemical  bacterial  products,  the  antibodies  ai-e  produced  as  new 
substances  within  the  or,i:;anism,  and  this  process  has  been  desi<;nated 
active  immunization  (Ehrlich);  in  the  case  of  the  injection  of  immu- 
nizing serum  the  antitoxin  alieady  fornuMl  is  introduced  from  without, 
and  this  may  be  spoken  of  as  passive  immunization.  It  is  pi'ol)abk' 
that  in  the  last  case  no  new-formation  of  antitoxin  occurs  after  the 
injection. 

For  the  foundation  researches  in  regard  to  inoculation  with  attenuated  cultures  of 
bacilli  cultivated  outside  of  the  body,  we  are  Indebted  to  Punteur,  wlio,  in  1880,  demon- 
strated the  fact  that  chickens  could  be  immunized  against  chicken-cholera  tlirough  the 
inoculation  of  cultures  of  cliicken-cholera  bacilli,  that  had  been  weakened  througii  long 
exposure  to  the  air. 

Since  that  time  numerous  experiments  have  been  carried  out  Avith  other  forms  of 
bacteria,  especially  with  attenuated  cultures  of  the  bacilli  of  anthrax  and  symptomatic 
anthrax.  Good  "results  have  been  obtained  from  inoculations  against  the  symp- 
tomatic anthrax  of  cattle.  Less  favorable  are  the  results  in  inoculations  against  an- 
thrax, in  that  some  of  the  animals  die  fVom  the  effects  of  the  protective  inoculation, 
while  others  are  not  rendered  absolutely  immune  against  a  new  anthrax  infection. 

Sheep  and  cattle  may  be  maile  immune  against  anthrax ;  most  expediently  (Koch) 
by  first  inoculating  them  with  attenuated  cultures  of  anthrax -bacilli,  which  will  kill 
mice  but  not  guinea-pigs,  and  then  with  those  which  will  kill  guinea-pigs  but  not 
large  rabbits. 

As  vaccine  against  symj^tomatie  anthrax,  there  may  be  used  cultures  of  the  bacillus 
I  attenuated  through  heat  or  such  chemical  agents  as  sublimate  solutions,  thymol, 
j  eucalyptol,  and  silver  nitrate;  and  by  such  inoculations  cattle  maybe  rendered  im- 
I  niune.  At  the  present  time  lieat  {Hens,  KM)  is  most  commonly  used  in  the  jjreparation 
,  of  the  vaccine.  The  infected  muscle  of  an  animal  dying  with  symptomatic  anthrax  is 
t  chopped  tine,  triturated  with  one-half  its  weight  of  water,  and  pressed  through  a  piece 
1  of  linen  cloth.  Finally,  the  fluid  is  again  filtered  through  a  moi.stciicd  jiicce  of  tine 
I  linen.  The  virulent  material  is  then  spread  in  thin  layers  upon  glass  plates  or  tlat 
i  dishes,  and  transferred  to  a  dry  chamber  at  a  temperature  of  3^35°  Q.  When  thor- 
I  oughly  dry  the  virus  is  scraped  off  and  removed  in  the  form  of  powder.  When  it  is 
'  desired  to  give  inoculations,  the  virus  is  triturated  with  double  its  weight  of  water  and 
!  the  tluid  evaporated  in  a  thermostat.  By  raising  the  temperature  to  100"  C.  for  six 
!  hours  a  weak  vaccine  is  obtained;  at  a  temperature  of  85°  C.  for  six  hours  a  stronger 
J  one.  For  the  immunization  of  cattle,  about  0.5  gm.  of  the  weaker  virus  in  a  dilute 
\  water  solution  is  injected  into  the  subcutaneous  tissue  of  the  animal's  tail,  and  alter 
I  eight  to  twelve  days  the  stronger  solution  is  similarly  injected. 

I  According  to  observations  of  Chanre.au  and  others,  protective  inoculations  may  also 
be  made  l)v  the  injection  of  virulent  bacteria  in  very  small  quantities,  or  in  sucli  a 
I  manner  that  the  life  of  the  animal  shall  not  be  endangered.  \\\  the  casc^of  syiniito- 
;  matic  anthrax  this  may  be  accomplished  by  the  injection  of  very  snudl  doses  into  tiie 
j  extremity  of  the  animal's  tail;  such  iniections  not  causing  a  fatal  illness,  l)ut  only  a 
i  local  disturbance. 

IAeconling  U)  Afanassieff,  it  is  po.ssible  to  render  animals  immune  l)y  inoculating 
the  granulating  surface  of  a  wound  with  a  virulent  culture. 
Cattle  may  also  be  immunized  against  contariioas  pleiiropiuiinionia  (Srlu'itz)  by  in- 
jecting the  tissue-juices  from  the  lung  of  an  animal  dying  from  this  disease  into  the 
tip  of  the  tail.  Tiiere  is  produced  in  this  way  a  circumscribed  inllammation,  or,  at 
I  least,  one  which  is  confined  to  the  tail;  after  recovery  from  which  the  animal  is  im- 
mune to  both  natural  and  artificial  infection  with  this  disease. 

Hogs  may  be  rendered  immune  against  inoculation  with  virulent  bacilli  of  Hirine- 
8 


114  THE    PROTECTIVE    POWERS    OF   THE    BODY. 

erysipelas  {Pasteur),  by  using,  as  vaccine,  cultures  attenuated  by  successive  inocula- 
tions" in  rabbits.  According"  to  ^/H/Hf?*/^;^,  rabbits  may  also  be  made  immune  against 
the  bacilli  of  swine-erysipelas  through  the  injection  into  the  car-vein  of  a  small  quan- 
tity of  a  virulent  bouillon-culture  diluted  with  fifty  times  its  volume  of  water. 

Animals  susceptible  to  iliphtlieria  may  be  rendered  immune  against  this  disease, 
according  to  Ikhring,  by  the  injection  of  cultures  of  diphtheria-bacilli  which  have  been 
weakened  in  virulence  by  exposure  for  sixteen  hours  to  iodine  trichloride  (1 :  500).  Two 
cubic  centimetres  of  such  a  culture  are  injected  into  the  peritoneal  cavity;  after  three 
weeks  this  injection  is  repeated  with  a  diphtheria-culture  (0.2  c.c.)  which  has  been 
■washed  four  days  in  bouillon  containing  iodine  trichloride  (1 : 5,500).  After  this,  fully- 
virulent  cultures  are  iniected  in  increasing  doses. 

Protective  inoculations  against  rabies  were  first  carried  out  in  cases  resulting  from 
bites  by  rabid  animals,  particularly  in  France  (Pasteur  Institute),  Russia,  and  Italy. 
As  inoculation-material,  the  spinal  cord  from  rabbits  which  have  been  infected  with 
rabies  is  used  after  it  has  been  dried  in  dry  air  at  a  temperature  of  23-25^  C.  ;  the  viru- 
lency  of  the  cord  being  gradually  lost  after  about  fifteen  days  of  the  drying-process. 
According  to  Protopopoff,  it  is  the  temperature,  and  not  the  drying  (Pasteur),  which 
lessens  the  virulence.  According  to  31arx,  the  micro-organisms  of  rabies  have  already 
been  weakened  in  the  body  of  the  rabbit.  Small  portions  of  a  rabbit's  cord  thus  weak- 
ened in  virulence  are  triturated  in  sterilized  chicken-broth  and  injected  subcutaueously 
into  the  bitten  individual;  at  first  pieces  of  cord  greatly  reduced  in  virulence  are  used, 
then  those  of  gradually  increasing  virulence.  According  to  the  view  held  by  Pasteur, 
the  spinal  cord  contains  both  the  microbes  of  the  disease  and  the  specific  poison  formed 
by  them;  if  the  latter  spreads  through  the  bodj'  more  rapidly  than  the  microbes,  it  con- 
fers an  inuiiuuity  against  a  subsequent  spread  of  the  microbes,  and  affords  protection 
to  the  nervous  system  in  particular.  In  order  to  confer  immunity  it  is,  therefore, 
necessary  to  introduce  as  large  a  quantity  as  possible  of  the  chemical  poison.  Accord- 
ing to  the  reports  of  the  Institutes  in  which  the  Pasteur  inoculations  against  hydro- 
phobia have  been  carried  out,  it  must  be  acknowledged  that  these  inoculations  have 
been  successful  in  preventing  cases  of  hydrophobia. 

Immunity  against  cliolcra  may  be  produced,  in  both  man  and  animals  {ILiffkine, 
Pfeiff'  r,  Kn//r,  Vn</,s,  and  other.s),  by  the  injection  of  sterilized  or  attenuated  cultures 
of  clinlcia-^pirilla  :  this  imniunity  (wiiich  is  of  short  duration)  depends  upon  the  forma- 
tion of  f<jiir,jir  h.irtt  rii-iihd  aiiti-hodies  in  the  blood  (see  Voges,  1.  c).  On  the  other  hand, 
we  do  not  "yet  possess  a  specific  remedy  by  which  the  life  of  any  animal  or  man  in- 
fected with  cholera  ma}'  be  saved. 

Inununity  against  typhoid  fever  may  be  secured  in  man  by  the  subcutaneous  injec- 
tion of  sterilized  cultures  of  typhoid-bacilli  (i^hjfigr,  Kolle);  and  the  establishment  of 
the  imnuinity  may  be  recognized  by  the  fact  that  the  blood-serum  of  the  individual  so 
inoculated  is  found,  after  a  few  days,  to  contain  bactericidal  substances.  Attempts  at 
immunization  in  cases  already  ill  with  typhoid  {Brieger,  Wassermann,  C.  Fraenkel) 
have  up  to  the  present  time  been  unsuccessful. 

According  to  the  reports  published  hy  KocJi  {Briiisli  Medical  Journal,  1897;  Deut. 
med.  Wochen.,  1897,  No.  16;  Centralbatt  f.  Bakt.,  xxi.,  p.  536)  of  the  investigations 
which  were  carried  out  during  the  winter  of  1896-1897  with  regard  to  the  cattle-plague 
in  Cape  Colony,  cattle  may  be  immunized  against  ''  Binderpest"  by  subcutaneous  in- 
jections of  10  c.c.  of  the  bile  taken  from  animals  dying  of  the  disease;  the  condition  of 
immunity  becoming  established  at  the  latest  by  the  tenth  day.  According  to  the  re- 
port of  Professor  Winkler  ("  Landwirthschaftl.  Bezirks-Verein  Giessen,"  AugTist.  IIKIO) 
hog's  and  cattle  may  be  immunized  against  foot-and-mouth  disease  through  feeding 
with  milk  of  animals  which  are  affected  by  the  disease  or  have  recently  recovered 
from  it.  Loeffler  and  I'hicnhuth  {Contralblaftf.  Bakt.,  xxix.,  1901)  have  also  reported 
successful  protective  inoculations  with  a  serum  against  the  foot-and-mouth  di.sease. 

In  the  year  1890  Koch  made  the  discovery  that  cultures  of  tubercle-bacilli  contain 
an  active  substance,  "tuberculin,"  which,  when  injected  into  tuberculous  individuals, 
causes  a  rise  of  temperature  and  to  some  extent  local  inflammatory  changes  in  the  neigh- 
borhood of  tuberculous  foci.  It  was  at  first  hoped  that  in  tuberculin  a  remedy  for- 
tuberculosis  had  been  found,  but  the  many  trials  made  with  it  upon  human  beings  and, 
animals  have  shown  that  it  indeed  produces  after  repeated  injections  an  immunity  1 
against  the  toxic  action  of  tuberculin,  but  does  not  hinder  the  multiplication  of  tubercle-  i 
bacilli  and  the  consequent  spread  of  the  disease.  Further,  the  local  infiammationi 
caused  by  the  tubercvdin  leads  to  favorable  results  only  under  special  conditions,  but, ; 
on  tlie  other  hand,  often  cau.ses  actual  harm  (through  the  metastasis  of  bacilli).  Never- 
tlieless,  Koch's  discovery  has  proved  of  great  importance.  In  the  first  place,  it  is  of 
practical  value  in  the  diagnosis  of  tuberculosis,  in  that  tuberculin  injections  do  not  ex-, 
cite  fever  in  normal  individuals.  Inoculations  for  diagnostic  purposes  are  now  used, 
very  extensively  in  cases  of  suspected  tuberculosis  in  domestic  animals.  Moreover,] 
the  reports  published  by  Koch  gave  a  great  stimulus  to  further  investigations  with  re- 


HEALING   sera:    VA(X'IXP:S.  115 

fftrd  to  immunization  by  means  of  inoculation  witii  bacterial  toxins;  and  these  investi- 
gations have  led  to  the  discovery  of  the  antibodies  of  diphtheria,  tetanus,  cliolera,  and 
vphoid  fever.  Small  doses  of  tuberculin  appear  also  to  have  a  favorable  influence 
ipon  the  course  of  tuberculosis. 

In  1897  AV// ("Ucber  neue  Tuberculinprilparate,"  Dent.  maJ.  Woch.,  1897)  suc- 
•eeded  in  obtaining  from  highly  virulent  cultures  of  tubercle-bacilli  a  substance 
vhieh  he  claims  is  able  to  immunize  against  all  of  the  constituents  of  the  tubercle- 
xicillus.  To  obtain  this  substance  youug  cultures  of  tubercle-bacilli  are  dried  in  a 
aeuum-exsiccator  and  then  triturated.  Tlie  product  obtained  by  trituration  is  mixed 
^  ith  distilled  water  and  ceutrifugated.  The  active  substauce  is  contained  in  the  muddy 
treeipitate  thus  obtained  (designated  by  Koch  as  T.  R.).  This  is  again  dried  and  tritu- 
ated,  dissolvetl  iu  water  to  wliicli  twenty  i)er  cent  of  glycerin  is  added  for  the  purpose 
f  preservation.  (The  i)reparatiou  is  manufactured  by  Mdntcr,  LucinH,  and  lirunning, 
i  lIochst-ou-the-Main,  Germany.)  Tiie  lluid  preparation  contains  10  mgm.  of  solid 
iibstance  iu  everj'  cubic  centimetre,  and  when  it  is  to  be  used  should  l)e  diluted  with 
ihysiological  salt  solution.  Through  the  use  of  large  doses  animals  are  said  to  become 
niuuuized  iu  from  two  to  three  weeks.  Iu  the  treatment  of  tuliereulosis  in  man  the 
ose  should  begiu  at  jj^  mgm.  and  gradually  be  increased  uj)  to  'M  mgm.,  llie  injections 
eing  given  every  other  day.  According  to  the  observations  so  far  ]Hil)lishctl,  the  T.  R. 
reparation  does  not  appear  to  exert  a  curative  action  upon  tul)erculosis  in  man. 

The  blood=serum  treatment  of  diphtheria,  i.e. ,  the  employment  of  the  antitoxins 
■lutained  in  the  blood  of  an  animal  immunized  against  diphtheria  as  a  means  of  curing 
lat  disease  when  it  is  already  contracted,  or  as  a  protection  against  such  infection,  is 
discovery  which  we  owe  to  Behring.  The  favorable  effects  of  the  method  discov- 
rcd  and  proved  by  him  through  experimental  investigations  liave  been  confirmed  by 
lousands  of  observations.  In  the  treatment  of  diphtheria  patients  a  large  quantity  of 
jie  serum  (one  thousand  immunizing  units)  is  usually  injected  at  one  time  beneath  the 
idn  of  the  thigh. 

j  The  term  " normal  serum" — i.e.,  a  serum  having  the  value  of  one  immunization 
init— is  used  by  Behring  to  designate  a  serum  which,  when  mixed  with  a  quantity  of 
jiphtheria  i)oison  equal  to  ten  times  the  minimal  fatal  dose  and  then  injected  in  the 
'uount  of  0.1  c.c.  into  a  guinea-pig  of  from  200  to  300  gm.  weight,  will  surely  protect 
lat  animal  from  diphtheria.  Sheep  and  horses  are  especially  adapted  for  the  prepara- 
;i)M  of  the  serum.  It  is  prepared  and  sold  in  doses  of  from  five  hundred  to  three 
[lousand  immunization  units. 

I  If  culture-tiltrates  of  the  tetanus^bacillus  are  weakened  by  the  action  of  chemi- 
;il  agents  (iodine  trichloride  or  iodine  combined  with  potassium  iodide),  it  is  possible 
rough  repeated  injections  of  such  filtrates  of  increasing  virulence  to  produce  im- 
unity  iu  animals  against  tetanus  {Kitasato,  Behring,  Tizzoni,  Bnchner).  The  blood  of 
jch  immunized  animals  contains  an  antitoxin  which  affords  a  sure  j^rotection  to  e.vperi- 
iital  animals  against  tetanus.  The  antitoxin  treatment  of  human  beings  sulTeriug 
om  tetanus  has  not  given  satisfactory  results  (see  Kohler  and  Schlesinger,  I.e.),  not 
en  iu  cases  of  relatively  early  injection  of  the  antitoxin,  though  it  appears  to  be 
["ective  if  administered  before  tlie  appearance  of  the  tetanus. 

Susceptible  animals  and  human  beings  may  be  immunized  against  bubonic  plague 
■  means  of  sterilized  cultures  of  tlie  pest-bacidus  {Tersin,  Ilaff'kine,  Kolle);  and  it  ap- 
ars  that  in  the  blood-senmi  of  immunized  animals  (the  horse,  for  example)  there  are 
esent  anti-bodies  which  render  the  serum  utilizable  for  both  protective  and  curative 
iirposes. 

j  Animals  may  be  made  immune  against  snecke-poisons  by  means  of  inoculations  of 
ry  small  doses  of  such  poison  continued  for  some  length  of  time  {Calmcttc,  Tschisto- 
\ti<ch)\  and  the  blood-serum  of  such  immunized  animals  is  also  found  to  possess  an 
••titoxic  action  against  the  given  poison,  so  that  it  maybe  used  as  a  healing-.serum. 
I  Brazil,  Mexico,  Africa,  etc.,  various  methods  involving  the  use  of  snake-])oison 
■jelf  are  employed  for  the  immunization  of  individuals  against  a  snake-bite,  or  for 
•jring  them  after  they  have  been  bitten  (drinking  of  the  secretions  of  the  i)oison- 
jmds,  rubbing  of  the  diluted  poison  into  small  wounds  of  the  skin,  etc.)  (Brenning). 

According  lo  the  investigations  by  Ehrlich,  mice  may  be  made  inuuune  against 
vin,  to  which  they  are  extremely  susceptible,  by  mixing  very  small  doses  of  ricin 
jth  their  food  and  then  afterward  injecting  additional  small  doses  subeutaneously. 
lie  appearance  of  the  inmiunity  occurs  on  the  sixth  day  after  the  admiinstration  of  the 
1  in,  so  that  upon  this  day  the  animal  can  withstand  aldose  thirteen  times  as  great  as 
ij  the  beginning.  Through  continued  systematic  iiioculations  the  animal  becomes 
iniune  to  a  dose  eight  hundredfold  us  strong.  The  inununity  is  produced  by  an  anti- 
t|<ic  body,  antiricin,  winch  neutralizes  tlie  poisonous  action  of  ricin. 

Vaccines.  Since  Wright's  discovery  of  the  opsonins,  bacterial  rarcines  have  been 
^;ensiv(ly  employed  in  the  treatment  df  certain  infections.  The  vaccinesare  prepared 
1  cultivating  the  given  organism  on  agar-agar,   suspending  the  growth  in  .salt-solu- 


116  THE    PROTECTIVE    POWERS    OF    THE    BODY.  ! 

tion,  and  heating  to  Go -80^  C.  for  an  hour  to  kill  the  bacteria.  The  emulsion  of  dea 
bacteria  is  then  fuiected.  Immediately  following  the  injection  the  opsonic  index  fal 
for  a  time,  the  so-called  negative  phase.  This  is  followed  in  a  day  or  two  by  a  rise  i 
the  index  to  or  above  its  original  height,  the  positive  phase.  Considerable  doubt  ht 
been  thrown  upon  the  opsonic  index  as  a  reliable  guide  in  the  progress  of  an  infectioi 
but  many  clinicians  have  obtained  gratifying  results  in  the  treatment  with  bacten;- 
vaccines  The  conditions  most  amenable  to  this  treatment  are  localized  inflammatior 
caused  bv  staplivlococci,  streptococci,  pneumococci,  gonococci,  and  the  tubercle-baci; 
lus.  As' the  me'thod  of  treatment  is  still  in  the  experimental  stage,  it  is  too  early  v 
make  definite  statements  concerning  its  value. 

\ttenipts  have  been  made  to  treat  thyroidism  with  a  specific  serum  {Bogers,  Leebe 
Experimental  immunity  to  Spirillum  obenneieri  can  be  produced  by  the  injection  ( 
filtered  blood  in  which  the  spirilla  have  died  out  (yovy).  Experimental  immunity  ci 
be  obtained  in  experimental  cerebrospinal  meningitis  (Flexner). 


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1 


IMMUNITY.  117 

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fungen gegen  Rausclibrand  im  Kant.^Bern  in  d.  J.  1882-89,  Bern,  1884,  188G  and 
18S9. 
3ogyes:  Lyssa,  Wien,  1897. 

issaeff:  Kiinstliche  Iminuuitat  gegen  Cholera.     Zeitschr.  f.  Hyg.,  xvi.,  1894. 
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fuiig.     Deut.  Zeit.  f.  Thiermed.,  xiii. ;  Cbl.  f.  Bakt.,  i.  1887. 
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Woch.,  1891. 
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18S4;  Neue  Tuberkulinprilparate.     Deut.  med.  Woch.,  1897,  No.  14. 
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inlogie  der  Heuleupest.     Deut.  med.  Woch.,  1897  (Lit.), 
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Heilversuche    gegenuber    d.  Infection    mit    Milzbrand-,    Tetanus-  u.  Diphtheric- 
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118  THE    TROTECTIVE    POWERS    OF   THE    BODY 


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solubles.     Ann.  de  rinst.  Past.,  1887;  Immunite  contre  le  cbarbon.    Ib.,  1888. 
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1898.  i 

Stern:    Ergebnisse  auf  d.  Gebiete  der  Immunitatslehre.     Cbl.  f.  allg.  Path.,    IBJj 

Wirkung  d.  menschlichen  Blutserums  auf  die  exper.  Typhus-Infection.     Zeit.! 

Hyg.,  xvi.,  1894.  { 

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TaruflB.:  Heilung  des  Tetanus  tniumaticus  durch  Antitoxin.     Cbl.  f.  Bakt.  xi.,  1892' 
Tavel:  Beitr.  z.  Blutserunitherapie  d.  Tetanus.     Corrbl.  f.  Schweizer-Aerzte,  1894.. 
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1S1)9. 
Vaughan  and  Novy:  The  Cellular  Toxins,  1902. 
Voges:  Die  Cboleraimmunitiit.     Cbl.  f.  Bakt.,  xix.,  1896  (Lit.). 
Wasserman:    Immunitat.    Eulenburg's  Jahr.,  iv.,  1894;   Zeit.  f.  Hyg.,   xxii.,   18  ; 

Serumtberapie.     Deut.  med.  Woch.,  1897;  Kiinstl.  Immunitat.     Berl.  klin.  Woe,, 

1898;    Seitenkettenimraunitat.     Ib.,  1898;    Neue  Versuche  auf  dem  Gebiete  jr 

Serumtberapie.     Deut.  med,   Woch.,  1900;  Naturlicbe  u.  kiiustliche  Imrauniit. 

Z.  f.  Hyg.,  xxxvii.,  1901.  '. 

Wechsberg:  Naturl.  Immun.  a.  bakterizide  Heilsera.     Z.  f.  Hyg.,  xxxix.,  1902.     j 
Weigert:  Arbeiten  zur  Tbeorie  der  Antitoxinimmunitat.     Ergebn.  d.  allg.  Path.,  |., 

1899. 
Welch:  The  Huxley  Lecture.     Bull,  of  the  Johns  Hopkins  Hosp.,  1902. 
Yabe:  Etude  sur  I'immunite  de  la  tuberculose,  Paris,  1900. 
Yersin:  La  Peste  bubonique.     Ann.  de  I'lnst.  Past.,  1897. 

See  also  g§  30,  31,  and  33. 

Hi.  The  Active  Substances  of  Acquired  Immunity.     Ehrlich's  Si:- 
chain  Theory. 

§  38.  Acquired  Immunity  depends  upon  the  i)resence  of  specific  ai  i- 
toxic  and  bactericidal  antibodies.  The  i)rocess  is  seen  in  its  simplest  fdoi 
in  tlic  i)rodiieti()n  of  sintitoxins,  a  plienomenon  most  familiar  to  nsiulie 
healing  of  diphtheria  and  tetanns.  : 

According  to  the  views  of  Ehrlich,  only  those  substances  are  poisis 
that  possess  a  chemical  affinity  for  some  element  of  the  body  and  throjh 
a  combination  with  this  e.\ert  a  harmful  action  recognizable  clinicay. 
A  congenital  immunity  to  poison  may,  therefore,  depend  upon  the  ,ct 
that  tlie  poison  linds  in  the  immune-body  no  element  with  which  it  in 
react  chemically,  or  the  element  so  affected  suffers  no  damage  in  a  cljii- 
cal  .sense.  Tn  acquired  immunity  to  poison  the  poisonous  action  of  le 
toxin  is  prevented  through  the  formation  of  an  antitoxin. 

Tlie  com])k'x  protoplasmic  substances,  when  considered  as  chemal 
structures,  consist  of  (Elirlicli)  a  (/onrniug-nncleus  or  central-group  (*'- 
trul  rinff)  and  of  various  .sidc-diains.  These  side-chains  can  combine  ^  tb 
the  side-chains  of  albuminous  nutritive  substances,  and  so  bring  abouai' 
assimilation  of  the  latter.     They  thus  have  the  signiticance  of  recej>rs 


i 


1 


EIIRLICIl  S    SIDE-ClIAlX    TJIKOHV.  119 

or  of  a  haptophore  group  which  combines  with  a  hapUyphorom  f/roitp  of  the 
albimiinous  food-material.  In  the  same  way  toxins  (trr  auc/iorcd  ihromjh 
their  h(q)top/ioroi(s  group  to  the  reeeptors  of  the  eell-protoplu.wi,  thus  em(]>liny 
the  toxophoroufi  group  of  the  toxin  to  exert  it,s  aetioii  upon  the  cell-protoplasm 
and  to  injure  the  rit<(l  powers  of  the  cells. 

As  the  result  of  the  combination  of  the  toxins  w  illi  llic  i('eei)tors,  i)oi-- 
tions  of  the  protoplasmic  albnmin-molccnle  ai-e  rendered  incai)able  of 
fnnctionating'.  Jf  the  life  of  the  cell  and  its  ])ower  of  compensation  are 
not  dama.u'ed,  there  is  i)roduced  only  a  functional  disturbance  of  tiie  cen- 
tral-jinmp  without  any  delinite  injury  to  it;  and  the  cell  may  apiin  re- 
place the  side-chains  and  even  form  them  in  excess,  throw  them  off,  and 
give  them  to  the  blood.  Such  detached  side-chains  or  receptors  constitute  an 
antitoxin.  The  antitoxin  is,  therefoi-e,  no  new  substance,  but  one  nor- 
mally jtreseut,  which  under  certain  coiulitions  is  ]>i<>duced  in  an  increased 
amount  and  o-iven  oil'  into  the  blood,  and,  circulating  there,  combines  the 
toxin  Jtreseut  in  the  blood  to  form  a  harmless  bod//,  and  so  prevod  its  action 
upon  the  cells.  The  sanu'  substance  in  the  living  body,  which  as  a  con- 
stituent of  the  cells  renders  intoxication  possible,  beconu's  the  cause  of 
healing  wheu  set  free  into  the  blood-stream  (vou  Behriug). 

The  bactericidal  action  of  ttieblood'^serum,  a  phenomenon  occurring 
in  certain  infectious  diseases  (typhoid  fever,  cholera,  plague),  is  depend- 
ent ui)on  the  combined  action  of  two  substances.  One  of  these  is  a  ferment- 
lil-e  body  found  in  the  tissue -juices,  and  particularly  in  the  blood-serum 
of  the  normal  organism.  It  is  very  labile  and  is  destroyed  by  heating 
to  55°  (\  Buchner  has  designated  this  substance  as  alexin,  Ehrlich  as 
complement  (earlier  as  addiment),  and  Metschnikoff  as  egtase.  It  alone 
is  not  able  to  injure  the  bacteria,  but  needs  for  this  action  the  coop- 
eration of  an  intermediate-body,  the  amboceptor  or  immune-body  of 
Ehrlich  (substance  sensibilatrice  of  Bordet). 

The  amboceptors  are  occasionally  formed  first  duiing  the  course  of  au 
infection,  and  are  specific  for  that  infectious  disease  (specific  immune- 
bodies),  that  is,  they  ai-e  active  only  in  that  disease  in  the  course  of 
which  they  are  formed.  They  possess  two  haptophore  groups,  one  of 
which  (cytophile  group)  combines  with  a  receptor  of  the  bacterial  proto- 
plasm ;  the  other  (complementophile  group)  combines  with  a  haptophore 
chain  of  the  complement,  so  that  the  zymotic  group  of  the  latter  can  act 
upon  the  bacterial  cells.  The  amboceptor  is  less  suscejitible  to  heat  than 
the  complement  and  is  not  destroyed  by  heating  to  60°  C. 

The  bactericidal  sera  act,  in  the  first  ])lace,  in  such  a  way  as  to  cause 
the  death  and  solution  of  the  bacteria,  in  that  tlic^  specific  immune-body, 
the  amboceptor,  carries  over  to  the  bacteria  the  digest i\e  action  of  the 
normal  body-juices,  in  the  complement,  so  that  the  bacteiia  are  in  part 
dissolved.  Such  sera  contain,  therefore,  bacteriolysins.  A  sectnid 
action  is  shown  by  them  in  the  phenomenon  of  agglutination,  in  that 
specific  substances  contained  in  the  serum,  the  agglutinins,  combine 
with  the  bacterial  cells  and  cause  a  characteristic  clumping  of  the  bac- 
teria contained  in  a  uniform  suspension.  The  agglutinins  are  less  sus- 
ceptible to  heat  than  are  the  lysius  and  are  not  changed  at  5()°  C. 

Finally,  bactericidal  immune-sera  cause  also  tlu^  i)henomenon  of  pre- 
cipitation, in  that  certain  substances  contained  in  the  same,  precipitins, 
or  coagulins,  foi-m  chemical  combinations  with  c<'rtain  snbstances  gixcn 
off  from  the  disintegrating  bacterial  bodies  and  coagulate  or  ])r«'cipitate 
them.  If  an  active  bactericidal  serum  be  added  to  a  clear  tluid  which 
contains  such  albuminous  substances  of  the  bacterial  cells,  there  is  quickly 
produced  a  flocculent  precipitate. 


120  THE    PROTECTI\'E    POWERS    OF   THE    BODY. 

Precipitins  withstand  beating  to  5G°  C.  and  may  be  dried  without 
losing  their  potency. 

According  to  Ebrlicb,  the  receptors  for  a  toxin  represent  only  a  hap- 
tophoroiis  group  of  the  cells  with  whose  haptophorous  chain  the  toxin  has 
combined.  He  designates  the  same  as  a  receptor  of  the  I  order.  On  the 
other  hand,  the  receptor  of  the  cells  for  the  nutritive  albumin-molecules 
contains  a  haptophorous  and  a  zymophorous  group,  the  latter  of  which 
causes  a  fermentative  disintegration  of  the  anchored  albumin-molecule. 
This  is  designated  as  a  receptor  of  the  II  order.  The  receptor  for  bacteri- 
olysiu  contains  a  haptophorous  group  for  the  anchoring  of  the  ferment- 
like  complement  and  a  receptor  for  the  combining  of  the  disintegration 
products  of  bacteria,  so  that  the  former  cau  act  upon  the  latter. 

The  receptors  tlirowu  off  by  the  cells  are  designated  by  Ehrlich  as 
haptins,  and  he  distinguishes:  ixhaptinofthe  I  order,  the  antitoxin,  which 
combines  the  toxin  to  form  a  harmless  body ;  haptins  of  the  II  order,  the 
agglutinins,  precipitins,  or  coagulins,  which,  after  their  union  with  the 
albumin  of  the  bacteria,  cause  agglutination,  coagulation,  and  precipita- 
tion through  the  action  of  the  zymophorous  group ;  and  haptins  of  the 
III  order,  or  bacteriolysins,  which  as  amboceptors  carry  over  the  fer- 
mentative action  of  the  comijlement  to  the  bacteria. 

Under  especial  conditions  there  appear  in  the  tissue-juices,  particularly  in  the 
blood,  substances  that  act  upon  the  red  blood-cells  or  tissue-cells  or  the  soluble  albumins 
of  the  human  and  animal  oriranism  in  the  same  manner  as  the  antibodies  described  above. 
According  to  their  action  tiiey  are  classed  as  haemolysins  (nlobulicidal  immime-sora), 
cytolysins,  precipitins,  and  agglutinins.  They  arise  when  into  the  body  of  an  ani- 
mal there  is  introduced  the  blood,  lymph,  milk,  oi'  tissue  from  an  animal  of  a  ditferent 
species  {B(ir<let,  Tsrhi.stoiritsch.  Kraus,  von  Dungern,  Wassermanri,  Ehrlich,  Mon/ai- 
roth,  Lundsteincr.  I'lilcnhuth.  and  others).  The  blood-serum  of  a  guinea-pig  injected 
repeatedly  with  defibrinated  rabbit's  blood  is  able  to  dissolve  quickly  in  vitro  the  red 
corpuscles  of  the  rabbit,  while  normal  guinea-pig's  blood  does  not  possess  such  a  power. 

The  action  of  haemolysins  or  of  a  globuUcidal  immune-serum  corresponds  in  all 
.respects  to  that  of  the  bacteriolysins,  and  the  researches  concerning  the  nature  of  the 
haemolysins  {Ehrlich.  M orgenroth)  have  aided  essentially  in  the  explanation  of  the 
mechanism  of  the  process  of  bacteriolysis. 

The  imnume-body  or  amboceptor  appearing  in  globulicidal  serum  shows  a  great 
specific  affinity  for  the  corresponding  erj-throcytes;  it  will  combine  with  them  at  0°  C. 
and,  when  thus  separated  from  the  complement  left  in  the  serum,  is  not  in  itself  able  to 
dissolve  the  red  blood-cells.  The  complement  will  not  combine  with  the  red  cells 
without  the  immune-body.  When  the  immune-body  or  amboceptor  is  present,  the 
complement  may,  at  a  higher  temperature,  be  carried  by  the  amboceptor  over  to  the 
red  cells  and  cause  their  solution. 

After  intraperitoneal  injections  of  laked  blood  of  the  same  species,  the  so-called 
isolysins  may  be  formed,  that  is,  the  blood-serum  of  the  animal  injected  acquires  the 
power  of  dissolving  the  red  cells  of  another  individual  of  the  same  species. 

Cytolysins  or  cytotoxins  arise  through  the  injection  of  foreign  cells  into  an  organ- 
ism, for  example,  after  the  injection  of  ciliated  epithelium,  spermatozoa,  leucocytes, 
renal  epithelium,  adrenal  cells,  brain-substance,  pancreas-cells,  placenta-cells,  and 
carcinoma-cells.  In  the  case  of  ciliated  epithelial  cells  and  spermatozoa  the  action  of 
the  cytolysins  contained  in  the  serum  can  be  recognized  outside  of  the  body  in  the 
rapid  cessation  of  movement  (tricholysin,  spermolysin). 

Cytolysins  act  in  the  same  manner  as  the  hsemolj^sins. 

Precipitins  arise  in  the  blood-serum  as  a  specific  reaction  of  the  body  after  the 
subcutaneous,  intraperitoneal,  or  intravenous  introduction  of  foreign  albuminous 
substances. 

A  serum  containing  precipitins  has  the  power,  when  added  to  the  albumin  solution 
u.sed  in  the  injections,  of  causing  in  the  latter  a  precipitate.  R.  Kraus  has  demonstrated 
this  action  first  for  cholera-spirilla,  that  is,  for  the  substance  of  the  bacterial  cell  brought 
into  solution.  The  serum  of  goats  previously  treated  with  injections  of  cholera-spirilla 
or  with  the  bacterial  substance  causes  a  precipitate  in  filtrates  of  cholera-cidtures  that 
contain  no  bacilli.     This  property  of  the  bacterial  precipitins  may  be  used  in  diagnosis. 

According  to  the   investigations  of  Tschistoivitsch,  Bordet,    Wassermann,  Schiitze, 


i 


PRECIPITINS    AND    AGGLUTININS.  121 

Ehrh'ch,  ^[orycuroth,  ^fyer!<,  Uhlcnhuth,  von  Dungern,  and  others,  such  precipitins 
;ire  also  formed  after  the  injection  of  foreign  blood,  milk,  inflammatory  exudates,  fresh 
;uk1  ilried  flesh,  etc.;  and  through  the  aid  of  this  nu>tiu)d  it  l)ecomes  possible  to  dis- 
tinguish from  one  another  not  only  tiie  red  l)lood-cells  of  ditTerent  species,  but  also 
tlosh,  milk,  semen,  etc.;  that  is,  the  precipitating  serum  of  an  animal  A,  that  has  been 
treated  with  an  albumin  of  an  animal  B  of  another  species,  will  precipitate  the  albumin 
t)f  B,  but  not  that  of  a  third  species. 

This  reaction  of  albmnin  obtained  by  biological  methods  {biological  method  of 
lijfarntiating  albumins,  Wassennann  and  Schiitze)  is  so  extremely  sensitive  that  the 
specilic  test  tor  albumin  is  possible  even  at  a  dilution  of  1 :  100 ,()()().  The  {)recipitin 
reaction  has  found  its  most  important  application  in  the  examination  of  blood-stains, 
Init  it  is  also  of  use  in  the  differentiation  of  different  kinds  of  meat,  milk,  etc.,  and  can 
lie  applied  also  to  the  differentiation  of  plant-all)umins. 

The  reaction  is  specific  for  the  albumin  of  different  species  of  animals  and  for  man; 
between  the  albumins  of  different  elements  of  the  body,  as^  for  example,  between 
chicken-blood  and  the  white  of  a  chicken-egg,  there  exist  only  quantitative  differences. 
.\n  antiserum  to  human  blood  will  precipitate  also  urine  containing  albumin,  puiulent 
exudates,  ascitic  fluid,  seminal  fluid,  etc.;  so  it  may  be  inferred  that  the  various  fluids 
nf  the  body  contain  the  same  receptors  as  those  of  the  blood-senun.  In  the  examina- 
tion of  spots,  stains,  etc.,  the  first  thing  to  be  determined  is  the  jiresence  of  blood 
iiruaiacum  test,  Teichmann's  test,  spectroscopic  examination).  When  this  is  de- 
termined, the  biological  test,  properly  handled,  gives  very  certain  results,  particularly 
when  the  animal  used  for  the  production  of  the  serum  is  not  closely  related.  An  anti- 
serum for  human  blood  gives  only  a  very  weak  reaction  with  ape's  blood  (particu- 
larly that  of  anthropoid  apes);  and  similar  conditions  exist  between  the  horse  and  the 
lonkey,  and  lietween  the  chicken  and  pigeon. 

For  the  demonstration  of  the  presence  of  human  blood  or  albumin,  the  serum  of 
rabbits  i^roperly  treated  beforehand  can  be  used  to  best  advantage,  but  that  of  the  horse, 
?heep,  or  goat  may  also  be  employed  (according  to  von  Dungern,  cold-blooded  animals 
iroduce  no  precipitins).  To  produce  the  antiserum  (Uhlenhuth)  5-10  c.c.  of  a  dilute 
^olution  of  albumin  derived  from  human  tissues  or  blood  are  injected  into  a  rabbit  at 
ntervals  of  several  days,  imtil  a  test  of  blood  taken  from  the  vein  of  the  ear,  made  about 
ive  days  after  the  last  injection,  shows  the  serum  to  be  active.  It  is  very  strange  that 
he  time  in  which  this  change  in  the  serum  occurs  varies  greatly  with  individual  animals. 
iVhen  the  serum  has  attained  its  full  strength,  the  animal  is  aiuesthetized,  the  thorax 
)l)ene<l,  and  a  cut  made  into  the  heart.  The  blood  flowing  into  the  tlioracic  cavity  is 
aken  up  by  a  pipette  and  collected  in  a  sterilized  glass  graduate.  The  serum  when 
separated  is  filtered  through  a  Berkefeld  filter  and  when  ready  for  use  must  be  perfectly 
•lear.     The  albuminous  material  to  be  tested  is  dissolved  in  physiological  salt-solution. 

A  serum  of  high  potency  may  contain  precipitins  that  act  not  only  upon  homo- 
iogous  albumins,  but  also  upon  heterologous.  Uhlenhuth  recommends,  therefore,  a 
'narked  dilution  (1:  1,000)  of  the  fluid  to  be  examined,  which,  moreover,  must  be  per- 
fectly clear.  To  2.0  c.c.  of  the  dilute  fluid  0.1  c.c.  of  the  antiserum  is  added,  and  in 
he  presence  of  homologous  albumin  a  cloudy  precipitate  forms  at  once  or  after  one  or 
I  wo  minutes. 

[  Agglutinins  that  cause  clumping  through  their  functional  molecule-groups  may 
lie  combined  first  with  bacteria,  but  also  after  that  with  red  blood-cells.  Agglutinable 
jubstances  and  agglutinins  possess  specific  combining  haptophore-groups  {Eisejiberg 
;nd  Volk,  Wassermann).  In  the  agglutinable  substance  the  functional  group  is  more 
jibile  and  more  easfly  destroyed  than  the  haptophore-group;  this  is  true  also  of  the 
^[glutinin  {Waf:sermann).  Through  external  influences  the  functional  group  may  be 
jst,  and  from  the  agglutinin  there  is  produced  an  agglutinoid,  which  is  no  longer  able 

0  catise  agglutination,  and  through  its  combination  with  tlie  ;igglutinable  substance 
s  able  to  prevent  the  occurrence  of  agglutination  in  the  presence  of  agglutinin.     As  has 

een  mentioned  above  (^5  31).  agglutination  has  been  observed  chiefly  in  the  case  of 
iliolera-spirilla,  typhoid-bacilli,  pyocyaneus,  colon,  and  tulierde  iiacilli. 

1  Immune-agglutinins  are  produced  during  the  process  of  immunization  by  an 
jicreased  formation  and  setting  free  of  groups  that  under  certain  conditions  occur  in 
[light  amount  even  in  normal  serum. 

I  Agglutination  can  be  applied  to  the  diagnosis  of  the  given  disease,  but  it  nuist  be 
i^membered  that  the  senun  of  healthy  individtials  causes  agglutination  (in  typhoid 
jn-ereven  in  dilutions  of  1 :  20,  while  the  sertmi  of  persons  having  the  disease  will  agglu- 
inate  at  a  dilution  of  1 :  50);  and  that  a  serum  can  also  agglutinate  to  a  greater  or  less 
■agree  other  liacteria  than  the  one  coming  under  the  influence  of  its  agglutination  power, 
the  serum  of  typhoid  patients  or  of  tho.se  immune  to  typhoid  acts  upon  many  colon- 
':>ecies  even  in  high  dilutions. 

The  precipitable  substance  in  culture-fluids  is,  according  to  Wassermann,  identical 


122  THE    PROTECTIVE    POWERS    OF   THE    BODY. 

tcith  the  aij'jlutinahh  substance  in  the  bacterial  cells;  that  is,  the  substance  present  in  the 
uninjured  hactcrial  cells,  combining  in  agglutination  with  the  aggkitinating  serum, 
is,  in  the  culture-fiuids,  dissolved  out  of  the  bacteria,  set  free  in  tlie  same,  and  gives 
there  a  specific  precipitate  with  the  serum. 

Agglutination  and  dissolution  of  the  bacteria,  according  to  Wassermann,  Ehrlich. 
Morycn7-i>th.  etc.,  are  not  caused  by  the  same  substance,  as  is  beHeved  by  von  Baum- 
garten  and  Gruber  to  be  the  case.  Agglutinins  and  amboceptors  or  immune-bodies  are 
two  bodies  distinct  from  each  other  and  do  not  have  the  same  haptophorous  group  in 
common.     The  immune-body  needs  for  its  action  the  complement,  the  agglutinin  does  not. 

The  agglutinin  is  made  up  of  separate  or  partial  agglutinins,  and  a  bacterial  agglu- 
tinin may,  therefore,  vary  in  its  constitution  according  to  the  biological  qualities  of 
the  animal  in  which  it  is  produced.  Two  varieties  of  bacteria  (typhoid-fever  and  colon- 
bacilli)  may  also  possess  a  number  of  partial  agglutmins  in  common.  It,  therefore, 
becomes  necessary  {Wa-ssermann),  when  applying  agglutination-tests  for  the  purpose  of 
diagnosis,  to  work  alwaj-s  with  such  dilutions  as  possess  a  limit  of  action  not  far  fron 
that  obtained  by  titration  for  the  given  bacterial  species  (the  limits  of  potency  of  am 
serum  may  vary  greatly).  A  positive  agglutination  is,  therefore,  decisive  as  pertaining 
to  that  species  with  wliich  the  animal  producing  the  serimi  was  previously  treated. 

The  production  of  antitoxin  plays  the  most  important  role  in  the  healing  o 
diphtheria  and  tetanus;  the  success  attending  the  prophylactic  and  therapeutic  us< 
of  these  antitoxins  has  already  been  mentioned  in  §  32.  Antitoxins  are  also  produced  ii 
the  course  of  infections  with  tlie  staphylococcus,  streptococcus,  pneumococcus,  intoxi 
cations  due  to  Bac.  botulinus  (sausage-poisoning)  and  the  Bac.  pyocyaneus,  but  tht 
results  of  the  therapeutic  applications  of  these  are  at  the  present  time  uncertain. 

Antitoxins  are  also  produced  in  poisoning  with  ricin,  abrin,  crotin,  pollen-toxin 
mushroom-poison,  snake- venom,  eel-poison,  and  the  poison  of  toads  and  spiders. 

The  toxin  is  not  destroyed  by  the  antitoxin.  When  snake-venom  {Calmetie)  i 
mixed  with  antitoxin  so  that  the  mixture  becomes  harmless  to  animals,  and  if  the  mor. 
thermolabile  antitoxin  be  destroyed  by  heating  to  68°  C,  the  mixture  again  become; 
poisonous.  The  same  tiling  may  be  demonstrated  in  the  case  of  the  toxin  and  anti| 
toxin  of  the  Bac.  pyocyaneus.  ; 

According  to  \Vassertnann,  the  substance  of  the  central  nervoiis  system  chiefl;: 
affected  by  tetanus  is  able  to  combine  with  the  tetanus  toxin  alter  the  manner  of  a 
antitoxin  and  so  render  it  harmless.  Tetanus  toxin  rubbed  up  with  the  brain  sut 
stance  of  a  normal  rabbit  becomes  so  weakened  that  guinea-pigs  can  bear  ten  time 
the  fatal  dose  without  damage.  According  to  RaTisom,  the  tetanus-poison  injected  i 
fatal  doses  into  pigeons  is  demonstrable  in  all  organs  except  the  central  nervous  syf 
tem,  with  which  it  has  entered  into  chemical  combination. 

Therapeutic  attempts  with  bactericidal  sera  have  up  to  the  present  time  nc 
given  such  good  results  as  those  of  antitoxic  sera.  In  the  first  place,  the  bactericid:' 
sera  have  no  influence  upon  an  existing  intoxication.  Further,  an  action  upon  tb 
bacteria  present  is  also  impossible  when  the  injected  serimi  finds  no  free  complemer' 
in  the  blood  of  the  patient  or  when  the  amboceptor  from  animal  blood  (horse  blooc: 
does  not  combine  with  the  complement  of  human  blood. 

The  agglutinins,  precipitins,  etc.,  can  in  turn  produce  in  the  organism  anti-ant 
bodies,  antiagglutinins.  antiprecipitins,  etc. 

Hypersusceptibility  or  anaphylaxis.  Animals  may  react  to  certain  toxic  c; 
foreign  substances  in  one  of  two  ways,  either  by  an  increased  resistance  or  immunity  (■ 
by  an  increased  susceptibility  (hypersusceptibility  or  anaphylaxis).  According  t 
Theobald  Smith,  Otto,  Rosenau  and  Anderson,  Gay  and  Southard,  etc.,  there  occurs  ; 
remarkable  toxic  action  in  guinea-pigs  as  the  result  of  an  injection  of  a  small  dose  • 
horse-serum  (.0001-. 1  c.c),  followed  after  ten  days  or  two  weeks  by  a  second  injectic; 
of  relatively  large  amount  (5  c.c),  the  reaction  being  characterized  by  severe  sjmipton 
with  death  within  one  hour.  This  reaction  is  specific  in  that  guinea-pigs  sensitize 
with  horse-.senim  do  not  react  to  the  second  injection  of  other  proteid  substances,  ar. 
xnce  versa.  The  reaction  following  a  second  injection  of  the  same  proteid  in  guine. 
pigs  appears  to  be  common  to  all  higher  forms  of  albuminous  substances  (white  of  eg' 
haemoglobin,  milk,  extract  of  peas,  bacterial  proteids,  etc.).  Simpler  albuminc 
substances,  such  as  peptone,  seem  to  have  slight  sensitizing  and  poisonous  propertie 
while  lower  nitrogenous  compounds  as  leucin  and  tyrosin  possess  none  at  all.  llyv^ 
susceptil>ility  in  the  guinea-pig  may  be  transmitted  by  the  female  to  the  ofTsprin 
The  iiypersu.sceptibility  may  persist  for  a  long  time  {Rosenau  and  Anderson).  Ti 
hypersusceptibility  produced  in  guinea-pigs  to  second  injections  of  bacterial  protei 
resembles  that  procluced  by  second  injections  of  horse-serum.  It  is  significant  th 
the  F^eriod  of  incubation  in  a  number  of  infectious  diseases  corresponds  to  the  ten  • 
fourteen  days  required  to  sensitize  animals  to  a  foreign  proteid.  (For  literature  s 
Anderson  and  Rosenau,  Jour,  of  Med.  Res.,  July,  1908.) 


ACQIIKED    IMMUXITY.  123 


Literature. 

{Acquired  ImmunUi/,   Ehrlich's  ^Sidc- Chain  llttonj.) 

Aschoff:  Fhrlich's  Scitenkettenthcorie,  Jena,  1902  (Lit.). 

von  Baumgarten :  Phauocytenlehre.     B.  v.  Ziof;.,  vii.,  ISOG;    Jahres1)er.,  1891-1904; 

Die  Ilainolyse.     JVstsehr.  f.  Jaffe,   Braunscinvoi<:,  1900;    1^.  klin.  Woch.,  1901. 
Bordet;   Les  serums  lieniolyaques.    Ann.  de  I'liist.  Past.,  xiv.,    1900;  Mode  d'action 

des  serums  cytolytiques.     Ibid.,  1901. 
Charrin:  L'immunite.     A.  de  phys.,  iv.,  1893;  Traits  de  path,  gen.,  ii.,  Paris,  1896. 
Corbette:  The  Action  of  Antitoxins.     Jour,  of  Path.,  vi.,  1899. 
von  Diinf;ern:  Globuliciiie  Wirk.  d.  tier.  Organismus.    Munch,    med.  Woch.,   1899; 

Imuumserum  gegen  Epitheh     Ibid.,  1899;  Beit,  z,  Immimitiitslehre.    Ibid.,  1900; 

Die  Antikorper,  Jena,  1904;  Bindungsverhaltnisse  b.  d.  Pritcipitionsreaktion.     Cbl. 

f.  B.,  xxxiv.,  Orig.,  1903. 
Ehrlich:   Ueber  Toxin  und  Antitoxin,  Berlin,    1901;     Miinch.    med.    Woch.,    1903; 

.^chutzstoffe    des  Blutes.    D.  med.  Woch.,  1901;   Verh.  d,  Ges.  d.  Naturforsch., 

Leipzig,  1902. 
Ehrlich  und  Morgenroth:  Hamolysine.     Berl.   klin.    Woch.,    1900;     Wirkung   und 

Entstehung  d.  aktiven  Stoffe  im  Serum  nach  d.  Seitenkettentheorie.    Handb.  d. 

path.  Mikroorg.,  iv.,  1904. 
Emmerich:  Bakterolyt.  Wirkung  d.  Nucleasen  u.  Nucleasenimmunproteide.      C.  f. 

B.,  xxxi.,  1902,  Orig. 
Engel:  Leitfaden  u.  klin.  Untersuch.  d.  Bhites,  Berlin,  1902. 

Friedberger:  Die  baktericiden  Sera.     Handb.  d.  path.  Mikroorg.,  iv,,  Jena,  1904. 
Gruber:  Zur  Theorie  der  Antikorper.     Miinch.  med.  Woch.,  1901. 
Hauser:  Serodiagnostische  Methode.     Miinch.  med.  Woch.,  1904. 
Jogs:  Mechanismus  der  Agglutination.     Z.  f.  Hyg.,  40  Bd.,  1902. 
London:  Cytolytische  Theorie  d.  Immunitat.    C.  f.  B.,  xxxii.,  Orig.,  1902. 
Lowit:  Niederschlagsbildung  bei  d.  Agglutination.    C.  f.  B.,  xxxiv.,  Orig.,  1903. 
Manwaring:  The  Application  of  Physical  Chemistry  to  Serum  Pathology.  (Various 

papers.)     Studies  from  Rockefeller  Institute,  vi.,  1907. 
Marx:  Einfiihrung  in  die  Serodiagnostik.     Z.  f.  Tiermed.,  vi.,  1902. 
Metschnikoff:  Sur  les  cytotoxines.     Ann.  de  ITnst.  Past.,    1900;    Immunitat    bei 

Infektionskrankheiten,  Jena,  1902;    Die  Lehre  v.    d.    Phagocyten.     Handb.  d. 

path.  Mikroorg.,  Jena,  1S04. 
Moxter:  Immunserum  gegen  Spermatozoen.     D.  med.  Woch.,  1900. 
Muir:  The  Action  of  Ha^molytic  Sera.     Lancet,  1903. 
Miiller:  Antihamolysine.     Cbl.  f.  Bakt.,  xxix.,  1901. 
Neisser  und  Wechsberg:  Wirkungsart  baktericider  Sera.     Mimch.    med.    Woch., 

1901. 
Noguchi:  The  Thermostabile  Anticomplementary  Constituents  of  the  Blood.     Jour. 

of  Exp.  Med.,  1906. 
Oppenheimer:  Toxine  und  Schutzstoffe.     BioL  Cbl.,  xix.,  1899  (Lit.). 
Pfeififer,  L.r  Die  moderne  Immunitatslehre.     Z.  f.  Hyg.,  43  Bd.,  1903. 
Piorkowski:  Die  spezifischen  Sera.     C.  f.  Bakt.,  Ref.,  xxxi.,  1902. 
Proscher  und  Pappenheim:    Die    theoretischen    Grundprinzipien  der    Immunitats- 
lehre.    Fol.  haem.,  i.,  1904. 
Sachs:  Die  Hamolysine  u.  ihre  Bed.  f.  d.  Immunitatslehre.    Ergeb.  d.  a.  Path.,  vii., 

1902;   Hamolysine  d.  normalen  Blutserums.     Miinch.  med.  Woch.,  1904, 
Silberschmidt:  Ergeb.  a.  d.  Immunitatsforschung.     Korr.  f.  Schw.  Aerzte,  1902. 
XJhlenhuth:  Pnizipitine.     Eulenb.  Jalu'l).,  ii.,  1904  (Lit.). 
Vaughan  and  Wheeler:  The  Effects  of  Egg-^\■hite  and  Its  Split  Products  on  Animals. 

Jour,  of  Inf.  Dis.,  1907. 
Wassermann:  Natiirl.  u.  kimstl.  Immunitat.     Z.  f.  Hyg.,  .37  Bd,,  1901.    Agglutinine 

u.  Priiziiiitine.     lb.,  42  Bd.,  1903;   Die  Grundziige  d.  Lehre  v.  d.  Imnuuiitat  u. 

Serumtherapie.    Z.  f.  arztlich.  Fortbildimg,  i.,   1904;    (iiebt  es   ein  biologisches 

Differenzierunffsverfahren    f.    Meuschen-    u.    Tierblut    mittels    der    Priizipitine? 

Deut.  med.  Woch.,  1904;   Entstehung  und  Wirkung  d.  aktiven  Stoffe  im  Immun- 
serum.    C.  f.  B.,  XXXV.,  Ref.,  1904;  Antitoxische  Sera.     Handb.  d.  path.  Mikro- 
org.. iv.,  Jena,  1904. 
Weigert:  Arbeiten   z.  Theorie  d.  Antitoxinimmunitiit.     Ergebn.  d.  allg.    Path.,   iv. 

1X99. 
Ziegler,  K.:  Serumdiagnose  verschied.  Blutarten.     Cbi.  f.  a.  Path.,  xiii.,  1902  (Lit.). 


CHAPTER  IV. 

Disturbances  in  the  Circulation  of  the  Blood  and  of 
the  Lymph. 

I.  General  Disturbances  of  the  Circulation  Dependent  upon  Changes 
in  the  Function  of  the  Heart,  Changes  in  the  General  Vascular 
Resistance  and  Changes  in  the  flass  of  the  Blood. 

§  34.  The  mass  of  blood  is  kept  coustantly  in  motion  by  means  of  the 
rhythmical  contractions  of  the  anricles  and  ventricles  of  the  heart.  The 
blood,  as  it  is  driven  into  the  elastic  tube  of  the  aorta  toward  the  periph- 
ery of  the  body,  meets  a  significant  degree  of  resistance,  which  is  caused 
by  the  friction  in  the  innumerable  divisions  and  subdivisions  of  the 
arterial  system.  This  resistance  occasions  a  relatively  high  pressure 
throughout  the  entire  arterial  system,  which  in  the  human  femoral  artery 
equals  that  of  about  120  mm.  of  mercury.  After  passing  through  the 
capillaries  the  blood  arrives  in  the  veins  with  very  little  velocity,  and 
stands  in  the  veins  under  a  very  slight  pressure,  which  varies  according 
to  the  location  of  the  vein,  and  is  greatest  where  a  high  column  of 
blood  rests  upon  the  lumen  of  the  vein.  In  the  great  venous  trunks  in 
the  neighborhood  of  the  thorax  the  pressure  is  usually  negative,  espe- 
cially during  inspiration,  as  the  thorax  during  this  stage  of  respiration 
aspirates  the  blood  from  the  veins  lying  outside  of  the  chest.  Only  dur- 
ing forced  expiration  does  the  positive  pressure  in  the  veins  rise  some- 
what higher. 

Assuming  the  mass  of  the  blood  to  be  constant,  the  degree  of  pressure 
within  the  aorta,  at  any  given  moment,  is  dependent  upon  the  work  of  the 
heart  and  the  resistance  in  the  arterial  system.  The  latter  in  turn  is 
dependent  upon  the  variations  in  the  total  diameter  of  the  combined 
cross-sections  of  tlie  blood-vessels,  due  to  the  elasticity  and  contractility 
of  the  arteries.  In  the  major  circulation  the  arterial  tone  is  very  pro- 
nounced ;  in  the  lesser  circulation  it  is  slight,  the  blood-pressure  in  the 
pulmonary  artery  being  only  from  one-third  to  two-fifths  that  in  the 
aorta.  Both  the  heart  and  the  arteries  are  under  the  influence  of  the 
nervous  system,  which  regulates  their  activity. 

The  activity  of  tlu^  heart  consists  in  rhythmical  contractions  of  its 
muscnlatnre;  and  its  normal  efficiency  presupposes  that  the  heart-mus- 
cle, and  also  the  cardiac  ganglia,  are  sound.  Every  disease  of  the  heart, 
therefore,  in  so  far  as  it  diminishes  the  contractile  capacity  of  the  heart- 
muscle  and  lessens  the  activity  of  the  ganglion-cells,  and  in  so  far  as  a 
lessened  functional  activity  of  certain  parts  of  the  cardiac  muscle  is  not 
compensated  by  an  increased  activity  of  other  parts,  will  diminish  the 
functional  capacity  of  the  heart. 

In  many  cases  in  wliicli  the  functional  capacity  of  the  heart-muscle 
is  impaired,  certain  anatomical  changes,  such  as  fatty  degeneration  and 
necrosis  of  its  cells,  can  be  demonstrated ;  in  other  cases  no  anatomical 

124 


I 


IMPAIRMENT    OF    CARDIAC    Fl  XCTIOiV.  125 

changes  can  be  made  out,  especially  in  those  cases  in  which  the  diminu- 
tion of  working-capacity  follows  the  exhaustion  caused  by  excessive 
overexertion.  This  may  occur  when  the  heart  is  forced  to  work  for 
some  time  only  slightly  above  the  normal,  but  under  unfavorable  condi- 
tions, as,  for  example,  in  cases  of  elc\ation  of  the  body-temju'rature;  as 
well  as  in  cases  when  for  a  short  ])eri()d  it  is  overworked  to  an  excessive 
degree.  Under  certain  conditions  disturbances  of  nutrition  and  intoxi- 
cations, such  as  occur  in  the  infectious  fevers,  as  well  as  a  sudden 
diminution  in  blood-supply  from  the  obstruction  of  a  coronary  arteiy, 
may  cause  au  insufficiency  of  the  heart  within  so  short  a  time  that  the 
heart-muscle  presents  no  recognizable  anatomical  lesion.  The  work  of 
the  heart  may  also  be  made  difficult  at  times  through  the  fornuition  of 
adhesions  between  the  epicardium  and  pericardium,  and  between  the  lat- 
ter and  the  contiguous  pleura,  in  consequence  of  which  the  contractions 
of  the  heart  are  hindered. 

Through  the  collection  of  fluid  in  the  pericardial  sac  in  the  course 
of  certain  diseases,  further,  through  marked  deformities  of  the  thoi-ax 
causing  au  abnormal  smallness  of  the  thoracic  cavity,  and  through  a  high 
position  of  the  diaphragm,  the  diastolic  dilatation  of  the  heart  and  the 
free  afflux  of  blood  from  the  veins  may  be  hindered  to  such  an  extent 
that  the  ventricles  receive  too  little  blood.  If,  following  pathological 
processes  in  the  heart-valves,  there  result  rents  or  distortions  of  the  flaps 
or  adhesions  between  them,  or  if  in  case  of  dilatations  of  the  heart  and 
the  valvular  orifices  the  valve-flaps  become  relatively  too  short,  there 
may  arise  those  conditions  of  the  auricular  aud  ventricular  orifices  known 
as  insufficiency  and  stenosis.  The  former  condition  is  characterized  by 
a  failure  of  a  valve  to  close  completely  during  the  diastole  of  the  auricle 
or  ventricle  lying  behind  the  given  valve ;  the  second  condition,  by  the 
fact  that  during  the  contraction  of  the  auricle  or  ventricle  the  valvular 
orifice  does  not  suffice  for  the  passage  of  the  blood  through  the  opening. 
The  effect  of  a  stenosis  is  that  of  ojiposing  additional  obstacles  to  the  out- 
flow of  the  blood  during  systole.  In  aortic  and  pulmonary  insuflici(Micy 
the  blood  regurgitates,  during  the  ventricular  diastole,  back  from  the 
great  vessels  into  the  ventricles ;  in  mitral  and  tricuspid  insufficiency  the 
systole  of  the  ventricle  causes  a  regurgitation  into  the  corresponding 
auricle. 

Finally,  there  are  not  infrequently  formed  in  the  heart  masses  of 
coagula,  Mhich  under  certain  conditions — in  case  they  lie  near  the  orifices 
— may  on  the  one  hand  interfere  with  the  proper  closing  of  the  valves, 
or  on  the  other  cause  a  narrowing  of  the  ostium. 

As  the  result  of  all  the  above-mentioned  ])atliological  conditions,  the 
efficiency  of  the  heart's  function  is  impaired,  so  that  in  a  given  time 
too  little  blood  passes  into  the  arterial  system,  the  aortic  pressure  conse- 
quently falls,  and  the  velocity  of  the  blood-current  is  diminished;  wliile 
in  the  venous  system  the  blood  collects  more  and  more,  and  the  venous 
pressure  rises.  There  is  consequently  an  InadeqtKde  Jllihu/  of  the  arteries 
throughout  the  entire  body,  varying,  indeed,  according  to  the;  degree  of 
contraction  maintained  in  individual  arterial  systems,  wliile  both  veins 
and  capillaries  are,  on  the  other  hand,  oveiliiled  with  bh)o(l.  'I'lieit^ 
develops,  therefore,  a  condition  of  general  venous  hyperaemia,  wiiich 
in  some  parts  may  become  so  nuirked  that  the  tissue,  because  of  the  en- 
gorgement of  the  capillaries  with  venous  blood,  aequires  a  blue-red,  ei/a- 
notic  appearance.  Wlien  the  difference  in  pressure  l)etween  the  arterial 
aud  venous  systems  becomes  reduced  to  a  certain  minimum,  the  circula- 


126  DISTURBANCES    OF   THE    CIRCULATION. 

tion  comes  to  a  staudstill,  while  the  right  side  of  the  heart  becomes 
greatly  distended  with  blood. 

Should  the  contractions  of  the  heart  from  any  cause  become  weak  and 
imperfect,  the  pulse-wave  also  becomes  small.  If  the  rate  of  the  heart- 
beat becomes  diminished  in  frequency,  the  arterial  system  empties  itself 
to  a  greater  extent  than  normally  during  the  pause  between  the  systoles. 

If  the  impairment  of  cardiac  efficiency  involves  the  left  heart  essen- 
tially, as  is  the  case,  for  instance,  in  valvular  disease  of  the  left  side,  the 
disturbance  of  circulation  is  manifest  first  in  the  systemic  arteries,  as 
well  as  in  the  pulmonary  vessels. 

In  stenosis  of  the  aortic  valves,  the  arteries,  if  the  heart's  action  re- 
main unchanged,  fill  but  slowly  and  incompletely  (pulsus  tardus).  In 
aortic  insufficiency  a  normal  or  even  an  increased  amount  of  blood  is 
thrown  into  the  arteries  during  systole  (pulsus  celer),  but  a  part  of  this 
flows  back  again  during  diastole.  In  both  cases  the  left  ventricle  be- 
comes more  and  more  distended,  the  emptying  of  the  left  auricle  is  hin- 
dered, its  cavity  also  becomes  dilated,  and  finally  the  blood  is  backed  up 
in  the  pulmonary  veins.  Owing,  however,  to  the  low  pressure  in  the 
pulmonary  circulation,  the  blood  is  readily  dammed  back  upon  the  right 
ventricle,  and  the  blood  stasis  may  finally  extend  beyond  this  into  the 
right  auricle  and  into  the  systemic  veins. 

Valvular  lesions  at  the  mitral  orifice  produce  similar  effects  upon 
those  portions  of  the  circulatory  apparatus  lying  behind  the  left  auricle, 
as  in  such  cases  there  is  x^roduced  also  a  condition  of  pulmonary  stasis, 
with  a  rise  of  pressure  in  the  pulmonary  arteries  and  veins ;  while  the 
left  ventricle  either  receives  too  little  blood  (stenosis)  or  during  its  con- 
traction drives  a  portion  back  into  the  auricle  (insufficiency). 

In  valvular  lesions  of  the  orifices  of  the  right  heart  the  damming  back 
of  the  blood  is  limited  to  the  veins  of  the  systemic  circulation,  while  in 
the  pulmonary  circulation  both  pressure  and  velocity  are  diminished. 
Further,  the  pressure  in  the  aorta  also  falls,  since  the  left  side  of  the 
heart  receives  too  little  blood. 

The  damming  back  of  the  blood  in  the  great  systemic  veins  may 
manifest  itself  by  venous  puJsaUons  in  the  neighborhood  of  the  thorax,  in- 
asmuch as  retrograde  waves  of  pressure  proceeding  from  the  heart  may 
pass  through  the  veins  toward  the  capillaries,  distending  the  veins  to 
such  an  extent  that  the  venous  valves,  particularly  those  of  the  jugidar 
bulb,  are  rendered  inadequate.  The  essential  condition  of  the  transmis- 
sion of  the  venous  x>ulsation  is  the  insuificiency  of  the  venous  valves. 
In  the  case  of  imperfect  function  of  the  valve  in  the  jugular  bulb,  a 
slight  pulsation  may  be  observed  even  during  normal  action  of  the  heart ; 
but  when  the  veins  are  distended,  and  particularly  in  the  case  of  tricus- 
pid insufficiency,  the  pulsation  becomes  much  stronger  and  extends 
fui'thei-  toward  the  j^eriphery.  If  the  tricuspid  is  adequate  the  venous 
pulsation  (presystolic)  is  only  the  expression  of  the  rhythmical  occur- 
rence of  a  hindrance  to  the  outflow  of  blood  from  the  veins  (negative  or 
normal  venous  pulse).  In  tricuspid  insufficiency  the  contraction  of  the 
right  ventricle  forces  blood  back  through  the  tricuspid  opening  into  the 
right  auricle  and  into  the  veins  beyond,  giving  rise  to  a  systolic  venous 
pulsation  (positive  venous  pulse). 

If  in  a  heart  affected  with  a  valvular  lesion  the  chambers  lying  be- 
hind the  lesion  become  distended  Avith  blood,  the  muscular  walls  of  ^hese 
chain heis,  in  case  they  are  otherwise  normal,  may  by  an  increased  ac- 
tivity compensate  for  the  valvular  lesion  within  certain  limits.     In  the 


f 


niPATRMENT    OF    CARDIAC    FI^XCTIOX.  127 

course  of  time  tlieio  results  an  increase  in  the  volume  of  the  heart-mus- 
ele,  a  hypertrophy  of  the  heart=muscle,  wliichenables  the  heart  to  carry 
on  its  increased  woik  for  an  indelinite  ])erio(l.  Such  comjx'nsation  fi-e- 
nuently  becomes  inadequate,  with  the  result  that  tlie  aoitic  i)ressure  is 
permanently  lowered,  while  the  venous  picssuie,  on  tlu'  other  hand,  is 
abnormally  hi!;li.  There  is,  at  the  same  time,  the  dan,u<'r  that  the  h<>art- 
muscle  may  in  time  become  exhausted,  or  that  a  ^•eI•y  sli^uht  illness  may 
render  the  heart  insutticieut.  Thus,  for  exami)le,  a  prolonged  quicken- 
ing of  the  heart's  rate,  by  shortening  the  diastolic  periods  of  rest,  may 
cause  cardiac  exhaustiou  and  insuthciency.  Arrest  of  the  heart's  action 
tiually  follows,  with  great  accumulation  of  blood  in  the  heait,  since  tlie 
heart  is  no  longer  able  to  drive  onward  the  mass  of  blood  entering  it. 

An  increase  of  the  heart's  action — that  is,  an  increase  ir.  the  fre- 
quency of  the  heart's  contractions,  these  at  the  same  time  i-emaining 
strong  and  complete — causes  an  increase  in  arterial  pressure  and  an  in- 
creased velocity  of  the  blood-current.  When  increased  demands  are  fre- 
([uently  made  upou  the  left  side  of  the  heart^ — as  freipiently  happens  in 
heavy  bodily  labor,  conditions  of  luxurious  living,  abnornuil  irritability 
of  the  cardiac  nerves,  etc. — the  left  ventricle  may  become  hypertrophic 
and  act  permanently  wdth  greater  force.  Inasmuch  as  the  quickening  of 
the  blood-stream  causes  the  right  heart  to  receive  a  greater  amount  of 
blood  during  diastole,  a  hypertrophy  of  the  right  ventricle  is  usually 
found  in  connection  with  the  hypertrophy  of  the  left  ventricle. 

Lessening  of  the  mass  of  blood  or  general  anaemia  from  the  loss  of 
blood  leads  temporarily  to  a  fall  of  pressure  in  the  aorta ;  but  if  the  loss 
o<^  blood  was  not  excessive,  the  blood-pi-essure  rises  again,  as  the  vessels 
adapt  themselves  to  the  changed  conditions,  and,  as  the  result  of  the 
stimulation  of  the  vasomotor  centre  through  local  aufemia,  show  a 
Lrreater  degree  of  contraction.  Under  normal  conditions  the  mass  of  blood 
is  quickly  increased  through  the  absorption  of  fluids,  and  later  by  a  re- 
i:eneration  of  the  blood.  Similarly,  in  anhydrsemia — i.e.,  a  diminution 
3f  the  water  of  the  blood — the  arterial  pressure  is  lowered  and  the  blood- 
eurrent  slowed.  After  severe  haemorrhages  the  arterial  pressure  is  low- 
i?red  for  a  greater  length  of  time,  the  circulation  is  slowed,  and  the  pulse, 
because  of  the  lessened  stimulation  of  the  vagus-centre  (Cohnheim),  is 
frequent  and  small. 

In  the  case  of  lasting  diminution  of  the  blood-mass — i.e.,  the  condi- 
tion known  as  chronic  anaemia,  which  occuis  under  varying  conditions 
!— the  vascular  system  is  im])erfectly  filled,  the  blood-pi-essui'c  lowered, 
uid  the  blood-current  slowed.  Both  heart  and  bloo(l-\ cssels  adai)t  them- 
;;elves  to  the  new  conditions  and  become  diminished  in  \olume.  Jn  the 
ease  of  a  marked  deficiency  of  haemoglobin,  degenerations  of  t'-e  heart- 
inuscle,  particularly  fatty  degeneration,  frequently  occur. 
i  Increase  in  the  mass  of  the  blood,  through  the  injection  of  blood  or 
lalt-solution  into  the  blood-vessels,  is  followed  in  animals  by  oidy  a  tem- 
porary increase  in  ])ressu]-e  and  in  the  velocity  of  the  blood-current.  A 
•etnrn  to  the  normal  is  brought  al)out,  partly  by  the  dilatation  of  a  part 
)f  the  vascular  system,  particulaily  in  the  abdomen,  and  ]»aitly  through 
he  elimination  of  the  surplus  from  the  vessels.  If  the  mass  of  blood,  as 
!he  result  of  some  especial  ])redisposition  or  of  higli  li\ing,  comes  to 
i-tand  in  an  abnormally  high  porportion  to  the  body-weight,  if  there 
exists  a  permanent  plethora,  the  pressure  in  the  aorta  becomes  ])erma- 
■lently  raised,  the  work  of  the  lieart  is  permanently  increas<'d,  and  there 
ievelops  a  corresponding  hypertrophy  of  the  heart. 


128  DISTURBANCES    OF   THE    CIRCULATION. 

When  the  arterial  blood-pressure  is  raised  there  occurs  an  increased  giving-off 
of  fluid  from  the  blood,  and  thereby  a  concentration  and  diminution  in  the  amount  of 
the  venous  blood;  in  lowering  of  the  blood-pressure  the  amount  of  fluid  given  off  is 
diminished  and  eventually  an  increased  taking-up  of  fluid  occurs.  This  change  in  the 
venous  blood  is  under  normal  conditions  compensated  for  in  the  lungs:  in  the  first 
case,  through  a  taking-up  of  lymph  from  the  lymphatics;  in  the  second  case,  through  a 
giving-off  of  lymph  to  the  lymphatics  (//ess;  "  Beeinflussung  des  Flussigkeitsaus- 
tausclies  zwisrh'en  Blut  u.  Geweben  durch  Schwankungen  des  Blutdruckes."  D.  Arch. 
f.  klin.  Med.,  Bd.  79,  1903). 

§  35.  Increase  of  the  general  vascular  resistance  may  occur  in 
either  the  greater  or  the  lesser  circulation,  and  results  in  au  increased 
pressure  behind  the  point  of  increased  resistance,  and  a  diminished  press- 
ure beyond  it. 

In  the  systemic  circulation  the  hindrance  may  lie  either  in  the  main 
vessel,  the  aorta,  or  in  the  arterial  branches,  whose  degree  of  contraction , 
maintains  and  governs  the  normal  pressure  in  the  aorta.  Vascular  con- 
traction involving  a  great  number  of  arteries  and  their  branches,  audi 
sufficiently  well  marked  to  increase  the  blood-pressure,  is  generally  a  .; 
temi>orary  phenomenon,  passing  off  with  the  relaxation  of  the  arterial  i  \ 
tension.  Nevertheless,  a  permanent  increase  in  the  aortic  pressure  with 
consequent  hypertrophy  of  the  left  ventricle  does  occur ;  and  this  cannot 
be  explained  otherwise  than  as  the  result  of  the  contraction  of  the  lumen 
of  the  smaller  arteries.  Transitory  arterial  contraction  and  increase  of 
pressure  occur  particularly  through  an  increase  of  the  amount  of  car-, 
bouic  acid  contained  in  the  blood.  A  permanent  increase  of  aortic 
pressure  is,  on  the  other  hand,  a  result  of  chronic  diseases  of  the  kidney,; 
in  which  the  secreting  parenchyma  is  destroyed.  Inasmuch  as  the  por- 
tion of  the  vascular  system  which  is  thus  cut  off  is  much  too  small  to 
cause  such  an  increase  of  pressure  throughout  the  whole  aortic  system, 
since  the  vessels  leading  to  other  organs  might  become  correspondingly 
dilated,  it  must  be  assumed  that  in  the  case  of  contracted  kidney  some 
other  hindrance  to  the  circulation  occurs  throughout  more  extensive 
vascular  areas.  This  hindrance  would  most  naturally  be  sought  in  the 
apparatus  which  normally  serves  to  keep  the  aortic  pressure  at  its  propei 
height,  namely,  in  the  smaller  arteries  of  the  body.  Whether  the  coudi 
tion  is  caused  by  nervous  stimuli  arising  in  the  kidney,  or  by  the  actioi, 
of  retained  urinary  substances  upon  the  vasomotor  centres  or  directly 
upon  the  \'essel- walls,  or  whether  the  heart  is  excited  by  nervous  stimul 
to  increased  action,  we  are  not  at  present  able  to  say. 

Increase  of  resistance  in  the  aorta  may  result  from  stenosis  of  thi; 
vessel,  as  occurs  in  rare  cases  at  the  isthmus,  or  from  congenital  narrow 
iugs  of  the  whole  aorta,  large  aortic  thrombi,  or  from  extensive  disease  o 
the  vessel-wall,  in  consequence  of  which  the  intima  is  rough  and  nodu 
lar,  the  entire  vessel  rigid,  inelastic,  and  unyielding ;  or,  finally^  from ; 
general  dilatation  of  the  vessel,  whereby  eddies  are  formed  in  the  blood 
stream. 

Lowering  of  the  total  resistance  in  the  systemic  circulation  is  pos 
si])le  Ihrougli  llie  relaxation  of  the  tone  of  a  large  part  of  the  arteries 
and  this  event  may  happen  when  the  vasomotor  centre  is  paralyzed,  o 
wlien  the  cervical  cord  is  divided  or  partly  destroyed  through  any  othe;  i 
process.     Since  the  blood,  in  this  case,  fliows  abnormally  quickly  fror  J 
the  firteries  into  tlie  veins,  the  difference  in  blood-pressure  between  th.i 
arteries  and  veins  is  lessened,  tlie  current  becomes  slower,  the  heart  r€ji 
ceivestoo  little  blood  during  diastole,  and,  finally,  the  circulation  mav 
come  to  a  standstill. 


INCREASED    BLOOD-PKESSIKE.  129 

Increase  of  the  resistance  in  the  pulmonary  circulation  occurs  most 
fre(|iuMi11y  as  tlie  result  of  disease  of  the  luiius  and  |>leura.  Adhesious 
of  the  pleura,  as  well  as  spiual  curvatures,  Mhieh  hinder  the  ex])ansion 
of  the  luntis  and  their  chauge  of  volume  duiiui;-  inspiration,  thereby  de- 
priving the  circulatiou  of  au  etticient  aid,  may  cause  such  increase  of 
pulmonary  resistauce.  Of  great  inllueuce,  moreover,  are  such  affections 
of  the  lung  as  idiopathic  emphysema,  retractions  and  indurations  of  the 
lung,  and  destruction  of  lung-tissue — all  of  which  lead  to  the  oblitei'a- 
tion  of  a  portion  of  the  pulmonary  capillaries;  fnrther,  (!ompression  of 
the  lung  through  pleural  exudate;  and,  linally,  compression  of  the  pul- 
monary arteries  by  aortic  aneurism  or  by  tumors. 

If  the  hindrance  is  only  slight,  the  blood  may  make  for  itself  a  new 
passage  to  the  left  heart  without  any  increase  of  pressure ;  the  rate  of  the 
current  in  the  blood-vessels  which  are  unobstructed  alone  being  increased. 
Greater  obstacles  cause  an  increase  of  pressure  in  the  pulmonary  artery 
and  the  right  heart,  and  if  the  condition  j^ersists  for  some  time  the  right 
ventricle  through  increased  exertion  may  become  hypertrophic.  This 
can  occur,  however,  only  when  the  heart-muscle  is  adequately  nourished 
and  when  the  mass  of  the  blood  is  not  diminished  to  correspond  to  the 
dimiiuition  of  the  area  of  the  pulmonary  vessels.  If  the  right  heart  is 
not  able  to  overcome  the  obstacles  in  the  pulmonary  circulation,  the 
blood  is  dammed  back  upon  the  right  heart,  and  e\'entually  upon  the 
systemic  veins. 

An  increase  of  the  pressure  in  the  right  side  of  the  thorax  hinders  the  en- 
trance of  the  ^•enous  blood  into  the  right  heart,  and  causes  an  accumula- 
tion of  blood  in  the  systemic  veins.  A  sudden  increase  of  pressure  may 
cause  a  retrograde  flow  of  blood  into  the  neighboring  veins. 

According  to  the  investigations  of  Bombcrf/,  Pussier,  BruJins,  and  Midler,  pneumo- 
cocri,  diiilithcria-bacilli,  and  the  Bacilhis  p^'ocyaneus  injure  the  circulatory  apparatus 
of  tlie  ral)t)ir  (leaving  out  of  the  question  the  dilatations  of  the  heart  that  occur  particu- 
larly in  diphtiicria) ,  in  that  they  cause  paralysis  of  the  vasomotor  centres  in  the  medulla. 
This  paralysis  leads  to  a  cFiminution  of  the  arterial  blood-pressure  and  to  a  change  in 
the  distribution  of  the  blood.  The  splanchnic  vessels  become  overfilled,  the  vessels  of 
the  brain,  skin,  and  the  muscles. become  empty.  The  heart  is  not  concerned  in  this 
disturbance  of  the  circulation.  In  general,  it  is  affected  secondarily  as  a  result  of  the 
deficient  fiow  of  blood  due  to  the  vasomotor  paralysis.  A  central  jxmdysis  of  tlie  vaso- 
motors  is  also  responsible  for  the  circulatory  disturbances  occurring  in  the  acute  infec- 
tions ;  and  is  the  chief  cause  of  the  failure  of  tlie  circulation. 

The  observation  that  hypertrophy  of  the  heart  follows  different  diseases  of  the 
kidneys  has  been  Interpreted  in  various  waj^s.  Some  writers  seek  the  cause  in  an  in- 
crease of  the  volume  of  the  blood  {Trauhe," Bnmhcrrier),  others  {Senator,  Eicald)  believe 
it  to  be  due  to  the  changed  character  of  the  blood,  while  others  {Ovll  and  Sutton) 
a.scribe  it  to  a  widespread  change  in  the  walls  of  the  small  arteries.  Ihihl  holds  that  it 
is  due  to  the  over-nourishment  of  the  heart.  According  to  the  investigations  made  up 
to  the  present  time,  there  can  be  no  doubt  that  the  hypertrophy  of  the  lieait  in  diseases 
of  the  kidney  is  dependent  upon  an  increase  of  the  aortic  pressure.  This  increase  is 
best  explained  by  an  increase  of  the  resistance  in  the  small  arteries  of  the  entire  bociy, 
jdue  to  the  contraction  of  the  .small  arteries.  This  contraction  must  be  brought  about 
{either  through  the  direct  action  of  the  urinary  substances  contained  in  the  blood  or  by 
[some  reflex  stimulus  from  the  kidneys,  or  finally  by  some  influence  exerted  upon  the 
vasomotor  centre.  It  is  possible  that  the  heaVt  also  may  be  excited  to  increased 
activity. 

Literature. 

(Disturbances  of  the  Circulation. ) 

Bamberger:  Ueber  Morbus  Brightii.     Samml.  klin.  Vortr.,  No.  173,  1879. 
7.  Basch:  Allgem.  Physiologic  u.  Pathologic  des  Kreislaufs,  Wien,  1892. 
9 


130  DISTURBAXCES    OF   THE    CIRCULATION. 

Cohnheim:  Vorlesungen  uber  allgem.  Pathologie,  Berlin,  1882. 

Giill  anil  Sutton:  Med.-chir.  Trausact.,  Iv.,  18.j2. 

Janowski:    Diaguost.   Bedeutuug    der  Pulsuntersuchuug.     Klin.  Vortr.,  Nos.    193. 

im.  Leipzig,  1897. 
Jlirgensen:  Eikrankung  d.  Kreislauforgane,  Insufficienz  des  Herzens,  Wien,  1899. 
Krehl:  J 'atbolo.gische  Physiologic,  Leipzig,  1904. 

Iiowit:  Ueber  die  Entstebung  des  Lungenodems.     Beitr.  v.  Ziegler,  xiv.,  1893. 
Iiukjanow:  Allgemeine  Patbologie  des  Gefiisssystems,  Leipzig,  1894. 
Mackenzie:  The  Venous  and  Liver  Pulses.     Journ.  of  Path.,  11.,  1893. 
Passler  u.  Roily:  Die  Kreislaufstorung    Im  Kollaps   bel   akuten   Infektionskrank- 

lieiten.     Miuicli.  med.  Wocb.,  1903. 
Romberg,    Passler,    Bruhns  u.  Mliller:    Kreislaufstorung  bel  acuten  Infections- 

krankheiten.     Deut.  Aim.  f.  kliu.  Med.,  64  Bd.,  1899. 
Rosenbach:  Herzkrankbeiten.     Eulenburg's    Realencyklop.;    Einfluss  der  Raumbe- 

scbrilukung  in  der  Pleurahoble  auf  den  Krei.slauf.     Virch.  Arch.,  105  Bd.,  1886. 
Thoma:  Patholog.  Anatomic,  i.,  Stuttgart,  1894. 
Vogt:  Exp.  Untersucb.  liber  anat.  u.  funkt.  Veriind.  d.  Herzens  bei  Entzundung  des 

Herzbeutels  u,  bei  Verschliessung  der  Kranzarterien,  Moscow,  1901. 

II.  Local  Hyperaemia  and    Local  Anaemia. 

§  36.  To  the  blood  is  assigned  the  function  of  supplying  all  the  or- 
gans and  tissues  of  the  body  with  nourishment.  The  cells  and  cellular 
structures  of  which  the  various  tissues  are  composed  are  able  to  maintain 
their  existence  without  the  advent  of  fresh  nutritive  material  only  for  a 
short  time ;  and  for  this  reason  the  majority  of  the  tissues  are  supplied 
with  blood-vessels,  and  those  not  possessing  vessels  of  their  own  are 
placed  in  the  most  intimate  connection  with  vascular  structures. 

The  demands  of  the  different  tissues  for  blood  are  not  always  the 
same,  and  there  is  consequently  in  the  various  tissues  a  corresponding 
increase  or  decrease  in  the  afflux  of  blood  and  in  the  amount  of  blood 
contained  within  an  organ  or  tissue  at  any  given  moment.  An  organ 
rich  in  blood  is  designated  as  hypereemic ;  one  poor  in  blood  as  anaemic. 

Tlie  regulation  of  the  amount  of  blood  which  an  organ  receives  under 
physiological  conditions  is  brought  about  by  a  change  of  the  resistance 
in  the  afferent  arteries ;  and  this  change  is  effected  entirely  through  a 
variation  in  the  calibre  of  the  arteries.  Since  the  total  mass  of  the 
blood  in  the  body  is  not  sufficient  to  fill  all  the  vessels  at  the  same  time, 
an  extra  supply  of  blood  to  one  organ  is  possible  only  by  supplying  a 
less  amount  of  blood  to  other  parts.  The  change  in  the  calibre  of  an 
artery  is  determined,  aside  from  the  blood-pressure,  by  the  elasticity  of 
the  artery-wall  and  the  degree  of  contraction  of  its  smooth  muscle-fibres. 
These  fibres  are  the  regulating  element;  their  activity  is  dependent 
partly  upon  influences  affecting  them  directly,  and  partly  upon  uer- 
Aous  influences  from  the  intravascular  plexuses  and  from  the  vasomotor 
centres  in  the  medulla  oblongata  and  in  the  spinal  cord,  some  of  these 
slimnlating,  others  inhibiting  the  muscular  action. 

When  the  departures  from  the  average  blood-supply  of  any  part  of 
the  body  overstep  the  physiological  limits,  or  if  such  variations  arise 
without  physiological  causes,  or  are  tmduly  prolonged,  the  condition  is 
spoken  of  as  pathological  hyper^emia  and  pathological  anaemia.  These 
conditions  arc  in  ]»ail  brought  about  by  the  same  regulating  mechanism 
which  governs  the  normal  blood-supply  of  an  oi-gan. 

Hyperaemia  of  an  organ  is  caused  under  pathological  conditions 
eitluT  l»y  an  increase  in  the  arterial  supply  or  through  an  obstruction 
and  damming-back  of  the  venous  outflow ;  and  there  are  distinguished, 
accordingly,  two  forms,  an  active  or  congestim  {arterial)  hypercemia  and 


HYPEK.K-MIA.  131 

a  jMSsive  or  stagiudlon  {venous')  hiipcrwrnia.  Active  hyperemia  arises 
tln'ous'i  '111  increase  of  ihe  afflux  of  blood  {eont/estion),  and  may  be 
either  idiopathic  or  collateral.  The  first  of  these  phiys  the  more  im- 
portant role.  It  depends  upon  a  rehixation  of  the  muscuhir  tunics  of 
the  artery,  which  may  be  brought  about  either  by  paralysis  of  the  i^aso- 
consirictors  (nruroparaJiftic  eouf/esfion),  oi-  thi'oni;h  a  .stimuUdion  of  the  vaso- 
dilators (neurotic  couf/estion),  or  throuiih  diivet  weakeniuf/  and  paraJi/sis  of 
the  muscles  (as,  for  instance,  by  heat,  brnisin^-,  action  <»f  atropine,  l)rief 
interruptions  of  the  blood-current),  or,  finally,  thronoh  a  diminution  of 
ilie  external  pressure  exerted  npon  the  vessels.  Collateral  hj/perwmia  is 
merely  the  result  of  a  diminished  flow  of  blood  to  other  i)arts.  It  oc- 
curs first  in  the  immediate  neighborhood  of  the  parts  whose  blood- 
supply  is  lessened;  later,  the  blood  may  be  driven  also  to  such  other 
more  distant  organs  as  may  require  it. 

Active  hyperemia  is  characterized  by  a  more  or  less  marked  redness  and 
sicellinf/  of  the  part,  which  are  very  striking  in  tissues  rich  in  blood-ves- 
sels. The  blood  flows  through  the  widened  channels  with  increased 
velocity,  and  gives  to  the  tissue  the  color  of  arterial  blood.  Superficial 
tissues  which  are  exposed  to  cooling  become  as  a  result  of  the  increased 
blood-supply  warmer  than  the  neighboring  tissues  which  are  less  richly 
supplied. 

Passive  Hypercemia  arises  through  the  retardation  or  obstruction  of 
the  fow  of  blood  fromthejveins.  A  general  passive  congestion  of  the  systemic 
veins  occuis  in  those  cases  in  which,  through  weakness  of  the  heart's  ac- 
tion, valvular  insufticiency  or  stenosis,  or  obstructions  to  the  pulmonary 
circulation,  the  emptying  of  the  large  veins  into  the  right  heart  is  hin- 
dered. In  the  pulmonary  circulation  stagnation  of  the  blood-stream 
imay  be  brought  about  by  any  cause  hindering  the  outflow  of  blood  from 
Ithe  lungs,  particularly  valvular  lesions  of  the  left  heart,  weakness  of  the 
Ileft  side  of  the  heart,  and,  more  rarely,  obstructions  in  the  systemic 
jarteries.  Not  infrequently  such  a  stasis  of  the  pulmonary  circulation 
imay  reach  such  a  degree  that  the  blood  is  dammed  back  into  the  right 
jheart,  and  into  the  veins  of  the  systemic  circulation  (see  §§  34  and  35). 

Local  passive  congestion  may  arise  directly  from  the  fact  that  the 
jprogress  of  blood  through  the  veins  is  not  adequately  su})ported  by  the 
activity  of  the  muscles  and  the  aspiration  of  the  blood  from  the  veins  dur- 
ing the  inspiratory  enlargement  of  the  thorax.  The  absence  of  the  first 
'factor  is  most  apparent  in  the  case  of  the  branches  of  the  inferior  vena 
jcava;  as,  for  examj)le,  in  individuals  who  pass  a  large  part  of  their  time 
kitting  or  standing  without  active  bodily  exercise,  so  that  the  emptying 
of  the  deep-seated  venous  branches  into  the  vena  cava  is  dependent  al- 
most wholly  upon  the  activity  of  the  vein-walls,  which  by  ^■irtue  of  their 
.elasticity  and  contractility  work  against  the  pressure  of  the  column  of 
blood  resting  upon  them.  The  absence  of  the  insi)iiat<uy  as]»iration  of 
jthe  venous  blood  may,  on  the  other  Juind,  make  itself  felt  in  distuibance 
pf  inspiration  through  inflammation  or  other  disease-processes  of  the 
lungs  or  pleura. 

A  further  cause  of  local  passive  hypersemia  consists  in  the  narrowing 
3r  closing  of  individual  veins,  as  in  the  case  of  compi-ession,  ligation, 
'"ormatiou  of  thrombi  (i^  38),  and  the  invasion  of  the  veins  by  new- 
growths.  For  example,  the  pregnant  uterus  or  a  pelvic  tumor  may  com- 
press the  ])elvic  veins,  a  thrombus  may  obstruct  the  cerebral  sinuses  or 
he  femoral  or  portal  veins,  or  a  sarcoma  of  the  pelvis  may  grow  into 
Ihe  large  pelvic  veins. 


132  DISTURBAXCES    OF    THE    CIRCULATTOX. 

When  throufih  the  above-mentioned  processes  or  through  ligation, 
single  A'eins  become  occluded,  the  effect  of  the  occlusion  is  often  very 
insignificant,  inasmuch  as  the  veins  concerned  may  possess  free  commu- 
nication with  other  veins,  so  that  but  slight  obstruction  is  offered  to  the 
outflow  of  the  blood.  If,  on  the  other  hand,  the  occluded  vein  possesses 
no  collateral  communications,  or  very  small  ones  which  are  inadequate 
for  the  passage  of  the  blood — as,  for  instance,  is  the  case  with  the  main 
divisions  of  the  portal  vein,  the  sinus  of  the  dura  mater,  the  femoral  and 
the  renal  veins — there  results  a  more  or  less  marked  passi^•e  congestion 
in  the  area  supplying  the  given  vein. 

The  effect  of  an  obstacle  to  the  outflow  of  blood  shows  itself  first  iu 
that  portion  of  the  vein  lying  between  the  obstruction  and  the  periph- 
ery, the  blood-current  becoming  slowed  or  checked  entirely,  while  at  the: 
same  time  there  follows  a  progressive  filling  and  dilatation  of  the  veins 
through  the  continued  affiux  of  blood  from  the  capillaries.  If  through 
the  counteractive  effect  of  the  increasing  tension  of  the  elastic  and  con- 
tractile vein-walls  the  obstacle  is  overcome,  the  circulation  is  main- 
tained, and  the  blood  flows  toward  the  heart  through  the  channels  whichi 
it  still  finds  open.  Is'ot  infrequently  the  small  Aeins  thus  called  upon  to' 
perform  this  increased  labor  become  gradually  much  dilated,  and  are. 
converted  into  larger  veins.  When  the  obstacle  cannot  be  overcome  and' 
communicating  vessels  capable  of  dilatation  are  not  present,  the  circula-, 
tion  comes  to  a  standstill,  and  a  condition  of  stasis  (§  40)  or  thrombosisj 
(§  38)  is  produced  iu  the  obstructed  vessel  and  its  tributaries.  i 

If  the  congestion  within  a  venous  area  extends  to  the  capillaries,  sc! 
that  they  become  overfilled  with  blood,  the  affected  tissue  becomes  blue^^ 
red  or  cyanotic,  exhibiting  at  the  same  time  a  cei'tain  degree  of  sivellmg.  \ 

Both  active  and  passive  hyperiemia,  observed  during  life,  may,  afteil 
death,  show  a  very  different  appearance,  and  not  infrequently  disappea:j 
entirely.     This  is  especially  the  case  in  the  active  hypersemias  of  tbi 
skin,  in  part  also  in  those  of  the  mucous  membranes.     This  is  dependenj 
upon  the  fact  that  the  tissues,  put  upon  the  stretch  by  the  dilatation  oj 
the  capillaries,  contract  upon  the  latter,  after  the  stoppage  of  the  ciij 
culation,  and  by  their  counter-pressure  drive  the  blood  from  the  capil; 
laries  into  the  veins.     In  this  way  a  tissue  which  was  red  during  lif' 
may  become  pale  after  death.     On  the  other  hand,  tissues  which  durin ' 
life  were  pale  or  at  least  showed  no  especial  redness,    may  after  deat 
take  on  a  blue-red  color.     This  takes  place  particularly  upon  the  sidt 
and  back  of  the  trnnk  (in  those  parts  not  pressed  upon  by  the  bod\ 
weight),  on  the  neck,  and  the  posterior  aspects  of  the  extremities  ( 
cadavers  lying  upon  their  backs;  and  is  to  be  explained  by  the  fact  thi 
after  death  the  blood  sinks  to  the  most  dependent  parts  of  the  body,  an, 
fills  not  only  the  veins,  but  finally  also  the  capillaries.     This  phenonn' 
non  is  known  as  post=mortern  hypostasis,  and  the  areas  of  discoloratici 
as  "  death=spots  "  or  livores.     They  appear  within  about  three  hou; 
after  death,  and  are  the  more  pronounced  the  greater  the  amount  ( 
blood  contained  in  the  skin  and  subcutaneous  tissues  at  the  time  of  deatl' 

In  the  internal  organs  post-mortem  hypostasis  is  particularly  notic 
able  in  the  ])ia  mater,  the  dependent  veins  being  usually  more  marked 
distended  with  blood  than  those  situated  higher.  In  the  lungs  the  se 
tling  of  the  blood  causes  an  engorgement  not  only  of  the  veins,  but  aL 
of  tlie  capillaries. 

If  the  general  circulation  during  life,  as  a  result  of  cardiac  insuf 
ciency,  is  imperfect,  and  there  results  a  general  passive  congestion,  t: 


jlj 


AN.EIMIA.  U.i 

blood  may  also  collect  iu  the  dependent  portions  of  the  body,  partly  be- 
cause it  is  not  dri\en  out  of  them,  and  partly  because  it  sinks  into  these 
parts  fi'om  those  situated  on  a  higher  level.  This  ])henomenon  is  also 
known  as  hypostasis,  and  occurs  particularly  in  the  lungs  (In/postatic 
congestion). 

For  the  observation  of  the  circulation  and  its  disturbances  durino;  life  the  tongue 
or  the  web  of  the  curarized  frog,  properly  spread  upon  a  glass  jilatc,  may  be  used 
i   (Cohit/ieiiii,  YiirJi.  Arch.,  Rd.  40).     This  may  be  done  in  a  very  simple  manner  by  draw- 
I   ing  the  frog's  tongue  over  a  cork  ring,  whieli  is  cemented  1o  a  glass  |)Iate,  and"  fasten- 
ing it  to  tile  sides  ot'  the  ring  with  pins      The  i)ulsaling  arterial  current  and  the  eon- 
tluuous  venous  stream  possess  a  clear  zone  of  blood-plasma,  in  bt)th  the  normal  and 
'   the  quickened  circulation.     If,  through  the  ligation  of  the  efferent  veins  of  the  tongue, 
!   passive  congestion  is  produced  and  the  current  slowed,  the  plasma-zone  in  the  veins  is 
I   lost,  and  both  veins  and  capillaries  become  greatly  distended  with  aec-umulated   red 
I   cells.     After  a  certain  time  the  tongue  swells  as  the  result  of  an  infiltration  with  trans- 
uded fluid. 

According  to  the  investigations  of  ron.  Landcrer  ("Die  Gewebsspannung,"  Leipzig, 

!   1884),  the  wall  of  a  capillary  vessel  embedded  in  tissue  supports  only  from  one-thinl 

1   to  one-half  of  the  blood-pressure.     The  remaining  jiortion  is  borne  by  the  tissues,  which 

afford  an  elastic  resistance,  and  thereby  maintain  ilie  tension  wliich  is  necessary  to  keep 

the  blood  in  motion.     In  both  active  and  passive  hypera^mia  l)oth  the  tissue-pressure 

and  the  tissue-tension  are  increased ;  in  anaemia  they  are  diminished. 

§  37.  Local  ansemia  or  ischasmia,  the  lack  of  proper  blood-supply 
to  a  tissue,  is  always  the  result  of  a  diminution  in  the  afliux  of  blood. 
If  the  total  mass  of  the  blood  is  normal,  the  cause  of  .the  anaemia  is 
purely  local ;  if  there  is  a  general  i:>overty  of  blood,  the  local  anaemia,  in 
part  at  least,  is  secondary. 

The  pathological  diminution  in  the  bIood=suppIy  to  an  organ  is  at 
times  merely  the  result  of  an  ahnoriiKd  increase  of  ihe  arterial  resistance, 
due  to  the  contraction  of  the  circular  muscular  coat.  According  to 
►Strieker,  Steinach,  and  Kahn,  the  capillaries  also  possess  a  power  of  con- 
j  tractility  which  is  under  the  inlluence  of  the  nervous  system.  In  other 
cases 2)fitholof/ieaI  obstructions — such  as  compression  of  the  arteries,  narrow- 
ing of  the  arterial  lumen  through  pathological  changes  in  the  vessel -walls, 
deposits  on  the  inner  surfaces  of  the  arteries,  occlusion  of  the  vessels  by 
emboli  (see  Fig.  2,  p.  65j,  etc.— may  act  as  hindrances  to  the  blood- 
stream. 

The  immediate  result  of  the  narrowing  of  an  artery  is  always  a  slow- 
ing and  dimimttion  of  the  blood-stream  beyond  the  point  of  constriction. 
Complete  ocdusion  of  an  artery  brings  the  circulation  beyond  the  obstruc- 
tion to  an  immediate  standstill.     If  back  of  the  point  of  constriction  or 
occlusion   the  artery    is  provided    with  large  arterial    communicating 
branches— the  so-called  orto-mZ  collaterals— the  disturbance  of  the  circu- 
'  lation  may  be  compensated  by  an  increased  afflux  of  blood  through  the 
'  collateral  arteries;  and  this  compensation  is  the  moie  conii)let«'  the  laiger 
!  and  t  lie  more  distensible  are  the  collaterals.     If  the  naiiowed  or  occluded 
artery  jiossesses  no  collateral  branches  in  its  area  of  distribution— if  it  is 
a  so-called  terminal  artery — the  slowing  or  cessation  of  the  circulation  be- 
yond the  point  of  obstruction  or  occlusion  cannot  immediately  be  done 
away  with,  and  the  affected  vascular  area  becomes  partly  or  wholly  emp- 
tied of  blood,  in  that,  through  the  contraction  of  the  arteries  and  the 
pressure  of  the  tissue  on  the  capillaries  and  veins,  the  blood  is  almost 
t  wholly  driven  out  of  the  area  supplied  by  the  obstriu-ted  artery.     Vn^- 
■  quently  there  occurs  after  a  time  an  al'llux  of  blood  from  tlu'  neighboiing 
!  capillaries. 
!        When  the  current  and  the  pressure  beyond  a  constricted  point  ha\e 


134  DISTURBANCES    OF   THE    CIRCULATION. 

sunk  to  a  certaiu  miuimum,  the  driving  force  gradually  becomes  unable 
to  propel  the  mass  of  blood.  The  red  corpuscles,  in  particular,  cease  to 
move,  and  collect  in  the  veins  and  capillaries,  so  that  the  area  supplied 
by  the  atiery  in  question  becomes  again  filled  with  blood  ;  only  not  with  cir- 
culating, but  with  stagnant  blood.  The  same  thing  occurs  when,  after  com- 1 
plete  occlusion  of  a  terminal  artery,  the  blood  slowly  and  under  low  press- 
ure enters  the  vessels  of  the  affected  area  from  small  arteries  incapable 
of  adequate  enlargement,  or  merely  through  anastomosing  capillaries. 
Finally,  an  accumulation  of  blood  within  the  anaemic  area  may  also  oc- 
cur by  a  reflux  from  the  veins.  This  takes  place  when  the  intravascu- 1 
lar  pressure  within  this  area  has  sunk  to  nothing  in  the  arteries  andj 
capillaries,  while  in  the  veins  a  positive  pressure  exists.  A  condition  of 
passive  congestion  in  the  veins  favors  such  a  reflux. 

A  further  cause  of  anaemia  of  one  organ  may  be  found  in  the  abnor- 
mal congestion  of  other  organs,  as  in  that  case  the  total  mass  of  the; 
blood  is  not  sufficient  to  supply  adequately  the  remaining  organs.  Such| 
an  anaemia  is  designated  collateral  anceniia. 

All  anaemic  tissues  are  characterized  by  ^joZewess.  At  the  same  time' 
they  are  flabby,  not  turgescent,  and  show  their  individual  color  more 
distinctly. 

The  significance  of  ischsemia  lies  especially  in  the  fact  that,  on  ac-| 
count  of  the  need  of  the  tissues  for  a  continuous  supply  of  oxygen  and; 
food-material,  the  persistence  for  a  certain  length  of  time  of  the  condi-! 
tion  of  imperfect  blood-supply  brings  about  tissue-degenerations  (compare 
§  1).  Total  arrest  of  the  blood-supply  leads  in  a  short  time  to  the  death\ 
of  the  tissue  involved.  If  the  blood  comes  to  flow  anew  into  the  degen^ 
crating  and  dying  tissues  in  the  area  of  distribution  of  an  obstructed  ves- 
sel, and  there  stagnates,  an  extravasation  of  blood  into  the  tissue  maj 
take  j)lace,  leading  to  the  formation  of  a  hcemorrhagic  infarct  (compart 
§44). 

Tlie  rapidity  and  completeness  of  the  clevelopme7it  of  a  collateral  circulation  after  tli( 
occlusion  of  an  artery  depends  upon  the  size  and  disteusibility  of  those  vessels  whicli 
are  in  communication  with  those  of  the  antemic  area.  If  these  are  numerous  and  dis  i 
tensible,  the  anaemic  area  is  soon  again  supplied  with  an  approximately  normal  volumij 
of  blood.  If  this  is  not  the  case  the  disturbance  of  the  circulation  is  more  slowly  conij 
pensated;  and  the  stasis  and  increased  pressure  are  found  to  extend  farther  back  froni 
the  point  of  obstruction  toward  the  heart,  so  that  a  collateral  hyperoemia  occurs  in  ves) 
sels  situated  farther  back  toward  the  heart.  In  the  further  course  of  the  process  o! 
re-establishing  the  circulation  the  resulting  increase  of  volume  and  velocity  remain  j 
confined  to  such  vessels  as  communicate  with  the  area  of  the  obstructed  artery,  that  isi 
confined  to  the  capillary  and  arterial  anastomoses,  where  the  increase  of  volume  and 
velocity  become  permanent.  This  leads  further  to  a  lasting  dilatation  of  the  vessel ; 
concerned,  and  at  the  same  time  to  an  increase  in  the  vessel-walls,  not  only  in  thickness; 
but  also  in  length,  as  is  evident  from  the  increased  tortuosity  of  the  vessels.  Accord  l 
ing  to  Notluuif/el,  the  phenomenon  of  the  increase  in  thickness  of  the  walls  of  the  anas] 
tomosing  arteries  may  be  demonstrated  in  the  case  of  rabbits  in  about  six  days  afte| 
the  ligation  of  an  artery  ;  and  after  the  ligation  of  large  vessels  in  their  continuity,  th' 
small  arteries  wliich  carry  on  the  collateral  circulation  become  changed  in  the  cours, 
of  a  few  weeks,  into  quite  capacious,  thick-walled  arteries. 

Literature. 

(Local  Disturbances  of  Circulation.) 

Baldwin:   jVIultiple  Aua;mic  Infarction  of  the  Liver.     Jour,  of  Med.  Research,  190;: 
(l-it.).  I 

Bier;  Kntstehung  d.  Collateralkreislaufs.  Virch.  Arch.,  147,  153  Bd..  1897,  1898  (Lit.'f 
Cavazzani:  Sur  la  genese  de  la  circulation  collaterale.  Arch.  ital.  de  biol.,  xvi.,  189S; 
Cohn:    Kliiiik  dcr  embolisclicn  Gcfasskranklicitcn,  Berlin,  1860,  I 

Cohnheim:   Vorlcs.  iibcr  aiigeincine  Palliojogie,  Berlin,  1883.  '! 

Hektoen:  Kinlx.lisin  of  the  Coronary  Arteries.     Med.  News,  1892.  1 


COAGULATION    AND    TllKOMUOSlS.  1J5 

Krauss:  DerYcrschluss  dor  Vena  Cava  sup.  u.  d.  Vena  Cava  inf.    Inaug.  Diss.,  Til- 

biiiircu.  1894  (Lit.). 
Lowitrmickliiutigc  Blutstromung.     Centralhl.  f.  alig.  Path.,  viii..  1897. 
Lukjanow:  Ailiicini'ine  Pathologic  des  Gefilsssystcins,   Leipzig,  1894. 
Marchand:  Gehinienibolio.     Beil.  klin.  Wochensciir.,  1894. 

Mdgling:  Zur  Keimtn.  des  luiinorriiagisclicn  LifaiUics.     Eeitr.  v.  Zieirlcr,  i.,  1886 
Nothnagel:  Die  EntstelnniudesCnllateialkreislaufs.     Zeitseli.  f.  klin'.  .Med.,  xv..  1888. 
V.  Recklinghausen:  Pathnlogie  des  Kreislaiil's  u.  der  I•:I■nall^uni,^  Stuttgart,  1883. 
Reimar:  Embolic  der.Vrt.  centralis  Hetiiiic.     Arch.  f.  Aiigeiilieiik.,  8S  P,(l.,  1899. 
Saveliew:  Gehirnartcrienenibolic.     Yircli.  Arch.,  13o  Bd.,  ISill. 
Steinach  u.  Kahn:  Kontractilitiit  u.  motor.  luuervat.  d.  Kapill.    Plll'ig.  A.,  97  Bd., 

1903. 
Talma:  Ceber  collaterale  Circulation.     Pfliiger's  Arch.,  23  Bd.,  1880. 
Thoma:  Pathologische  Anatomic,  i.,  Stuttgart,  1894. 
Virchow:  Ocrtliche  Storuugeu dcs  Kreislaufs.     llandb.  d.  spec.  Patli.,  i.,  Erlangen. 

1854. 

III.  Coagulation,  Thrombosis,  and  5tasis. 

§  38.  Upon  the  death  of  the  individual  tlie  blood  contained  in  tlie  lieart 
and  great  vessels  sooner  or  later  coagulates  in  part,  and  there  arise  those 
formations  which  are  known  as  post=mortem  clots.  If  the  clotting  oc- 
curs at  a  time  when  the  red  blood-cells  are  still  evenly  distribnted  in  tlie 
blood,  the  whole  mass  of  the  blood  becomes  coagnlated,  forming  soft, 
dark-red  masses  of  coagnlnm  which  are  known  as  cruor.  If  before  the 
clottiug  there  occurs,  through  the  sinking  of  the  red  cells,  a  separation 
of  the  blood  into  two  layers — a  substratum  rich  in  red  blood-corijuscles, 
and  an  upper  fluid  layer  containing  none  and  consisting  only  of  the 
plasma — then,  if  the  latter  coagulate,  there  will  be  formed  soft,  gelat- 
inous, light -yellow,  elastic  lumps  and  stringy  masses  having  a  smooth 
surface  and  not  adherent  to  the  vessel-wall,  which  are  known  as  lardace- 


Bto.  12. — A  iardaceous  clot  from  the  cadaver,     (rornialin,  h:i>matoxylin,  and  eosin.)     X  500. 


OUH  elotn  uv  ■A^fihrinoiiH  dejmsits.  These  contain  the  same  fibrin  threads 
(Fig.  12)  and  scattered  red  and  while  blood-cells.  Tlirongli  the  inclu- 
sion of  red  cells  in  these  formations,  they  mtiy  i)resciil  in  ])arts  a  red  or 
reddish-black  color;  if  lai'ge  nunijjers  of  leucocytes  are  ])ies('nt,  Ihey  may 
have  ii  whitish  color. 

^y/^e)l  blood  is  drawn  from  an  artery  or  vein  and  receised  into  a  vessel, 
co«*7«/«^/o«  will  occur  within  a  short  time,  as  the  result  of  the  adhesion 
of  the  fluid  to  the  sides  of  the  receptacle.  The  entire  blood-mass  be- 
comes changed  into  a  soft  coherent  mass.     When  freshly  drawn  blood  is 


136  DISTURBANCES    OF   THE    CIRCULATION. 

beaten  with  a  solid  body,  the  surface  of  tlie  latter  becomes  covered  in  a 
very  short  time  ^vith  felt-like  Jibrin.  If  within  the  body  large  quantities 
of  blood  pass  out  into  the  tissues— na,  for  example,  into  the  pericardium  or 
into  the  \\mgs,—eoa(]ulation  may  occur  here  likewise,  and  the  extravasated 
blood  may  ill  this  way  acquire  a  firm  consistency    (Fig.  13,  d). 

Under  certain  conditions  there  may  be  formed  withiii  the  heart  or 
Uood-vessels  during  life,  firm  deposits,  which  in  part  are  similar  to  cruor, 
and  in  part  to  the  fibrin-masses  formed  by  whipping  the  blood.  These 
formations  aie  known  as  thrombi,  and  the  process  which  leads  to  their 
formation  as  thrombosis.     According  to  their  color  they  may  be  distin- 


f/ 


--.r  s 


K  ^W 


I  a  d\  ^ 

Pig.  IS— fm^niiit  111  ii  f  1  111  1  III  in  inf  i  t  f  tl  e  l\in  niullpr  s  fluid  hematoxylin 
and  eosin  )      (    \l       I  |ti   \    1      t  i  ii  1  i       ni   ii  in         i  ill  ii       nil    \\\  tli  dirk  bluish-violet,  homo- 

geneous thi   mill    1  /    s  1 1 L      111       11     nil  1  1  111  I  II    1  \  ith  I    I  thiombus     d,  cJj,  alveoli 

filled  with  hiin  bljj  I  (.1  t      t    ^UlIiIiH    Iwiilisi   u^tluiiniiiu    ai  I  It  ii  uotes     X  90 

gulshed  as  red,  colorless  or  white  (that  is,  yellow  or  grayish- white),  an(? 
mixed  thrombi. 

The  coagulation  of  the  blood  is  a  peculiar  process,  difficult  of  exact 
interpretation.  Histologically,  it  is  characterized,  both  in  extrayaseulai' 
clotting  (Fig.  13,  d,  dj  and  in  intravascular  as  well  (Fig..  14),  by  the 
formation  of  little  I'ods  and  threads  between  the  red  cells,  at  one  time  ar- 
ranged in  a  meshwork,  at  other  times  in  stellate  or  fascicular  groups 
around  centres.  These  little  rods  and  fibres  are  known  as^ibrin  ;  and 
are  in  iiart  smooth  and  shining,  in  part  covered  by  little  granules,  or 
partly  interrupted  by  granules,  or  are  composed  entirely  of  such  collected 
together.  Besid(;s  the  threads  there  occur  also  free  granules,  gramdar 
masses,  and  blood-plates  of  varying  size  and  form ;  and  not  infrequently 
such  formations  lie  in  the  centre  of  the  fibrin-stars.  At  times  the  stellate 
and  fascicular  foinis  of  fibrin  are  found  arranged  about  leucocytes  or  at- 
tached to  endothelial  cells  of  the  intinia  of  the  vessel. 

In  the  red  blood-cells  there  occur  here  and  there  degenerative  appear- 
ances, in  the  form  of  plasmolysis,  plasmorrhexis,  and  plasmoschisis.  In 
plasmoli/sis  or  eri/throci/toli/sis  thei'e  occurs  a  passage  of  soluble  substances 
from  the  red  cells  into  the  blood  plasma,  so  that  the  red  cells  become 
smaller,  and  the  so-called  microcytes  and  red  blood-cell  "shadows"  are 
produced.     At  the  same  time  individual  cells  may  become  swollen. 

In  plasmorrhexis  or  eri/throci/torrhcxis  and  in  plasmoscliisis  or  erijthro- 
cytoschisis,  bright,  shining  globules  arise  from  the  red  cells,  or  the  latter 


COAGl  LATIOX    AND    THROMBOSIS.  137 

become  covered  with  little  prickle-lilce  projections,  or  come  to  resemble 
mulberries,  or  send  out  protoplasmic  ])rocesses.  Throujili  the  sn:uin<;-- 
off  of  these  prominences  round,  disc-like,  angular,  or  thiead-lik<'  bodies 
are  fornu'd,  Avhich  are  partly  homo<ieneous  aiul  partly  finely  jiranular, 
and  not  infrequently  enclose  lars:,i'r  shilling;' bodies.  Finally,  the  led  cells 
may  break  up  into  discdike  or  globular  ]neees,  and  finally  into  i;ianuk's. 
The  formations  known  as  h/ood-jilafcs  ixra  for  i\\i\  i<:\v<iivr]r,ivt  pccididr/i/ 
fonnrd  products  of  pla-smorrhcvis  and  plasino.schisifi  of  the  red  cff/.s ;  and  it  is 
possible  to  distiuii-uish  among*  them  those  Mdiich  are  colorless,  those  con- 
taining; haemoglobin,  and  homogeneous  and  granular  foi'uis. 

In  fresh  coagula,  changes  cannot  usually  be  demonstrated  in  the  color- 
less corpuscles  of  the  blood;  but  in  the  later  course  of  the  process  degeneia- 
tive  appearances  are  found  in  these  also;  and  products  may  thereby  be 
produced  resembling  those  arising  through  the  disintegration  of  the  red 
blood-cells  designated  as  blood-plates. 

Between  the  destruction  of  the  red  Nood-eells,  respectivehj  the  fonnation 
of  the  hlood-plates,  and  the  eoaf/ulation  of  the  blood,  both  extra-  and  infra- 
vascular,  there  exist  undoubtedhj  close  relations;  that  is,  coagulation  is 
set  into  action  through  the  occurrence  of  changes  in  the  red  cells  as 
above  described.  According  to  our  present  knowledge,  it  must  be 
assumed  that  many  red  cells,  probably  the  oldest  ones,  very  easily 
suffer  such  changes,  so  that,  for  example,  adherence  to  a  diseased  por- 
tion of  the  vessel-wall,  which  is  prevented  by  the  normal  condition  of 
the  intinia,  is  sufficient  to  cause  a  disintegration  of  certain  red  cells,  with 
formation  of  blood-plates,  and  later  coagulation  and  thrond)us- forma- 
tion. The  origin  of  coagulation  has  also  been  regarded  as  due  to  plas- 
molysis  and  plasmorrhexis  of  the  leucocytes ;  further,  similar  degenera- 
;  tions  of  the  endothelium  may  also  induce  coagulation.  The  possibility 
'  that  the  endothelial  cells  play  a  certain  part  in  the  origin  of  coagulation 
i  cannot  be  excluded,  but  it  must  be  emphasized  that  the  degenerative 
I  changes  ordinarily  preceding  coagulation  cannot  be  demonstrated  in  these 
■c^lls.  The  facts  brought  forth,  particularly  by  Hauser  and  Zenker,  that 
the  fibrin-threads  not  infrequently  are  attached  to  endothelial  cells,  or 
[leucocytes,  or  to  the  remains  of  such  cells,  do  not  pi-o\e  that  these  are 
jtlie  exciters  of  coagulation,  or  that  they  offer  material  for  the  foi-mation 
lof  fibrin ;  inasmuch  as  the  deposit  of  the  fibrin  upon   these   cells  may 

be  due  to  purely  mechanical 

--c!!^"'^  .  causes. 

The  chemical  processes 
concerned  in  coagulation  can- 
not at  present  be  exi)lained. 
It  is  assumed  that  for  its  oc- 
currence the  presence  of  a 
fibrinogejiic  substance,  a  fer- 
ment (thrombin),  and  certain 
s(dts,  particularly  c«/c/»*»  salts, 
is  necessaiy;  and  that  the 
librinogenic  substance  is  an 
albuminoid  body  belonging  to 
the  (/lob ul ins,  Avhich  is  i)resent 
^^'*    f  ^  '    ~^^'  in    the    blood-plasma,    while 

^^^'  ^ '2  ^^  the  ferment  is   i)roduced    by 

14.-Bundles    and    star-shaped   clusters   of   nbrin       ^^^^    CClls.        According    to   A. 

^"^!?i".„*„!f'?l'±^*^**^*^';    'r'''P°  **^'''"^  Prepara-      Schmidt,  thrombin  is  derived 

from  a  })arent-sul)stance,  pro- 


«~            •• 

\ 

//              -       -Mt. 

j'^ 

(    \ 

/ 

'^ 

^ 

/. 

,;^) 

f 

/              '       ,, 

>-       t 

^  ^  . 

>* 

» 

^ 

r 

iken  from  an  inflamed  tracheal  mucous  membrane. 


138 


DISTURB AXCES    OF   THE    C1RCULATIOX-. 


I 
T„n   if^—^potion  through  a  red  thrombus  formed  in  ( 

X2o0.  i 


thrombin  which  becomes  active  under  the  influence  of  a  zymoplashc  snl- 

sUince      By  means  of  the  thrombin  there  is  formed,  in  an  as  yet  unknown 

manner,  fi'omthe  gk)bnlins  pre-existing  in  the  all^aline  solution,  a  greatly 

swollen'albuminoid  body,  which  j^i^^j, 

is  precipitated  by  the   calcium  w.=.*f?H?S¥tf^i 

salts  contained  in  the  plasma. 

In  the  process  of  coagulation  we 

must,  therefore,    recognize  two 

stages,  namely,  the  stage  of  the 

production  of  the  fibrin-ferment, 

and  the  stage  of  the  action  of  the 

ferment  or  coagulation  proper. 

Morawitz  is  also  of  the 
opinion  that  fibrin-ferment 
arises  through  the  cooperation 
of  several  substances,  thrombo- 
gen,  tliromhoMnase,  and  calcium. 
The  substance  designated  as 
thrombokinase  is  identical  with 
the  zymoplastic  substance  of 
Sclimidt  and  behaves  in  the 
same  way  as  a  ferment. 

The  red  thrombus  is  formed 
under  such  conditions  as  the  com- 
plete stoppage  of  the  circulation  or 
a  marJced  slowing  of  the  same,  ami  precipitated  I 

comprises  the  tota    mass  «*  ^he  led  celM^ig.  io;  ^^^  ^^^^ 

fibrin  forms  granules  (Fig.  lo,  ^)  ^^^^^^^^^^^ 

small  vessels,  it  is  not  l^^^-fllX  ^  S^^^^^^  ^^^^  star-shaped: 

by  means  of  special  methods    the  pi e^enceoi  |>;^  ^  coagula-! 

cLters  of  fibrin-rods  (Fig.  ^f^'^^^^^^t^mgnisi^^ 

blood  occurinng  in  such    nflamnuxto^^^^^^^^^^^  ^^^  ^.^^. 

^  ^f  "V^rF?^' U)  anX^^  ^^  a  pale  appearance,  it  is  eyiden, 
£fthe1:i^b£oicelTsL\-thegi^^^         part  must  have  become  disinte; 

^'Immediately  after  its  formation  the  red  thrombus  is  soft  and  rich  h 
the"of  thl  blood;  later  it  becomes  tougher   denser,  and  -oe  dry 

tirbliod-pigS  m^^^^^^^^  changes  similar  to  those  occurring  m  ev 
'"'X' cause  of  the  ante=mortem  intravascular  coagulation  is^t; 
found  either  in  an  increase  in  the  production  ^  J^'-^'^J'^'^'^Za^S^c^ 
substances  or  in  a  dinwudion  of  the  power  possessed  ^^^  ff;*^' "f^^^d  ^ 
cfinMbiting  coagMion.  Under  certain  conditions  ^^^f  "\^^^  "^J^^'itse 
hesion  of  the  blo„d  to  a  degenerated  area  m  the  vessel-wall  may  in  i^^^^ 
be  snlhcient  to  induce  coagulation.  This  occ'urs  accordiiigh  in  Ivitt 
ves^ls,  when  the  endothelium  at  the  point  of  ligation  is  mjurexl;  but 
thf^ase  of  a  slight  injury  to  the  vessel-wall  and  the  blood,  clotting  m. 
not  take  place  (Baumgavten). 


I 


THROMBOSIS. 


lao 


White,  mixed,  and  often  distinctly  laminated  thrombi  arise  iti  the 
flowing  hlood,  and  consist  of  masses  of  yellowish  color,  or  of  various 
shades  of  red,  or  of  alternating  layers  of  red  and  white.  The  nnero- 
scopical  examination  shows  them  to  consist  of  granular  and  thread-like 
masses  (Figs.  IG  and  17),  leucocytes,  and  red  cells,  which  in  varying  i>i()- 


% 


t^^j^^ 


Fig.  16.-Spftion  fr 

iin  a  mixed  thrombus  rich  in 

no.  ir.— Section  from 

a  whitf  thnimlius  contain- 

cells.   (Miiller'sliuiil. 

lutiiatoxylin.)    a,  Redblood- 

ing  but  few  cells.     i.Miil 

er's  Iluid  ;    iKi-iiiato.wlin.) 

cells;   b,  granular  iiii 

ssfs;   c,  reticular  fibrin  con- 

0,  Granular  masses ;   //, 

Ilbn.irianular   lliiriu  imin- 

taining  many   leiicoc 

vtt's;   (I,  threads  of  fibrin  In 

Ing  a  net-like  reticulum; 

c,  Ubriu-thruads  in  parallel 

parallel  airaugement. 

X  200. 

arrangement.    .■   2tl0. 

portion  and  arrangement  make  up  their  stnictnre.  White  thrombi  may 
consist  almost  entirely  of  granular  masses  (Fig.  17,  a)  and  fibro-granu- 
lar  fibrin,  which  in  some  cases  is  arranged  in  a  meshwork  {b),  in  others 
in  fibres  running  nearly  parallel  (e)  which  enclose  few  leucocytes.  In 
other  cases  the  number  of  cells  may  be  much  greater.  In  mixed  thrombi 
(Fig.  10),  granular  fibrin  (b),  more  rarely  hyaline  nuisses,  thready 
fibrin  (e,  d),  and  red  blood-cells  (a),  in  varying  proportion  and  in  alter- 
nating stratification,  constitute  the  thrombus-mass,  and  all  of  these  ele- 
ments enclose  more  or  less  numerous,  often  many  leucocytes.  The  color- 
less portions  of  mixed  thrombi  consist  essentially  of  fibrin,  Iluid,  and 
leucocytes,  but  they  often  contain  also  numerous  tlecolorized  red  blood- 
cells. 

The  fihrogranular  masses  which  form  ])ait  of  the  structure  of  the 
throndjus  are  composed  of  precipitated  fibrin.  The  granular  and  hgaline 
masst-s,  on  the  other  hand,  jjrobably  aris<^  diicctly  from  the  products  of 
theplasmoschisisand  plasmorrhexisof  the  red  blood=cells,  in  ])ai  ticnlar 
from  the  blood-plates.  In  large  thrombi  they  often  show  a  coial-like 
arrangement. 

The  causes  of  the  formation  of  white  and  mixed  thrombi  aie  es- 
pecially: changes  in  the  iiiliina  of  the  heart  and  l/ie  re.s.se/s  and  di.'^ease.s  of  the 
vascular  apparatus,  that  lead  to  n  genend  or  local  slowing  or  irregular  it//  oj 
the  blood-stream. 

The  formation  of  thrombi  may  l)e  studied  directly,  in  suitable  sulijects,  under 
the  microscope,  both  in  the  case  of  cold-blooded  and  warm-blooded  animals;  and  (lie 
observations  made  in  this  line,  especially  by  Bizzozcro,  Jiljcrth,  .Schinititclhusrit,  and 
Lowit,  have  led  to  very  imjjortant  results. 

When  the  blood  flows  with  normal  velocity  through  a  blood-i/essel,  there  may  be 


140 


DISTURB AXCES    OF   THE    CIRCXJLATIOX. 


FIG.  19. 


seen  under  the  microscope  a  broad,  homogeneous  red  stream  in  the  axis  of  the  blood- 
vessel  (Fig.  18,  a),  while  at  the  sides  there  lies  a  clear  plasma-zone  (6)  free  from  red 
cells.     This  may  be  observed  in  the  arteries,  veins,  and  large  capillaries,  but  is  best 

seen  in  the  veins,  while  in  the 
small  capillaries,  which  are  just 
large  enough  to  permit  the  pass- 
age of  the  red  cells,  this  difference 
between  the  axial  stream  and 
plasma-zone  is  not  present. 

In  the  axial  stream  the  differ- 
ent constituents  of  the  blood- 
stream are  not  recognizable;  in 
the  plasma -zone  there  appear, 
from  time  to  time,  white  blooil- 
corpuscles  (Fig.  18,  d]  which  roll 
slowly  on  along  the  vessel-wall. 

If  the  blood-stream  becomes 
retarded  to  about  the  degree  that 
the  red  cells  of  the  axial  stream 
are  indistinctly  recognizable  (Fie. 

19,  a),  the  number  of  white  corpus- 
cles which  roll  slowly  along  in  tlie 
plasma-zone,  at  times  adhering  to 
the  vessel-wall,  becomes  constantly 
increased  (Fig.  19,<:/),  so  that  they 
finally  come  to  lie  in  great  num- 
bers in  this  zone. 

If  the  current  is  still  further 
retarded  so  that  the  red  cells  be- 
come   plainly    recognizable    (Fig. 

20,  a),  there  appear  in  the  periph- 
eral  plasma-zone,    in  addition  to  I 
the  colorless  blood-corpuscles  ((/),  ! 
also    blood-plates    (b),    which    in-  \ 
crease  more  and  more   in  number 
with   the  progressive    retardation  ' 
of   the   current,   while  the    leuco- 
cytes again  become  diminished  in  I 
numbers.      "When  total   arrest   of  i 

a  distinct  separation  of  the  corpus-  ' 


c 


Fig.  18.— Rapidly  flowing  blood-stream, 
h,  marginal  zone  with  isolated  leucocytes, 
and  Schimmelbusch.) 

Fig.  19.— Moderately  slow  blood-stream, 
b.  periplieral  zone  with   numerous   leucocytes. 
Eberth  and  Schimmelbusch.) 

Fig.  20.— Markedly  slow  current. 


a,  A.xial  stream : 
ff.     (After  Eberth 


o.  Axial  stream ; 
a.      (After 


Axial  stream ; 
th  blood-plates ;  c,  coll 
leucocytes.     (After  Eberth  and  Schimmelbusch. 


the    blood-current   finally  occurs,  there  follow 
cular  elements  in  the  lumen  of  the  vessel. 

If,  in  a  vessel  in  which  the  circulation  is  retarded,  the  intima  is  injured  at  a  certain 
point   by  compression   or   crushing,  or  by  means    of   chemical   agents,   as   corrosive 
sublimate,  nitrate  of  silver,  or  sodium  chloride,  and  if  the  lesion  of  the  wall  does  not  i 
lead  to  a  complete  stoppage  of  the  circulation,  hlood-platcs  may  be  seen  adhering  to  the  ■ 
injured  portion  of  the  wall;  and  in  a  short  tune  the  injured  spot  is  covered  with  many 
layers  of  the  same  (Fig.  20,  c).     Often,  more  or  less  numerous  leucocytes  (f/,)  become 
embedded  in  this  mass,  and  their  number  is  the  greater  the  more  numerous  these  are  : 
in  the  plasma-zone.     Under  certain  conditions  they  may  be  very  numerous  and  partly  , 
cover  up  the  blood-plates.     In  case  of  great  irregularity  of  the  circulation  or  more 
severe  changes  in  the  vessel-wall,  red  cells  may  also  drop  out  of  the  circulation  and 
become  adherent  to  the  vessel-wall  or  the  colorless  deposit  already  formed.     Xot  infre- 
quently portions  of  the  thrombus-mass  are  again  torn  loose,  in  which  case  a  new  de- 
posit of  Ijlood-plates  occurs.     The  vessel  may  finally  be  closed  as  the  result  of  a  long- 
continued  deposit  of  the  blood-elements. 

\\  hen  at  any  point  blood-plates  in  large  numbers  have  become  adherent  to  the 
vessel-wall,  they  become  after  a  time  coarsely  granular  at  their  centre,  and  finely, 
granular  or  homogeneous  at  their  periphery,  and  become  fused  together  into  one  com- 
pact mass.  The  final  result  of  this  process  is  the  formation  of  a  colorless  hlood-platc 
thrombus,  within  wliich  more  or  less  numerous  leucocytes  may  be  imprisoned.  Eberth 
designates  tiie  sticking  together  of  the  blood-plates  as  conglutination,  their  fusion  into  a 
coherent  throml)Us-mass  as  viscous  metamorphosis. 

According  to  the  investigations  of  Gutschy  the  first  steps  of  coagulation  consist' 
in  the  precipitation  of  a  gelatinous  mass;  and  to  this  " primary  fibrin-membrane"  theij 
blood-plates  and  later  the  other  formed  elements  of  the  blood  catch,  and  may  remain 
fastened. 

If  we  compare  the  observations  made  upon  warm-blooded  animals  by  Bizzozero, 


THROMBOSIS.  141 

Eberth,  and  Schtmryielbusch,  and  more  recently  by  Liiwit  and  Gutschy,  with  the  liis- 
tological  findings  in  thrombi  occurring  in  the  human  subject,  we  are  warranted  in 
drawing  the  conchision  that  the  formation  of  tlirumbi  in  tlic  circulatinL'-  blood  of  man 
occurs  in  part  in  the  same  way  as  that  observed  in  the  lower  animals.  'Ihronibosis  is, 
therefore,  directly  dependent  upon  two  causes:  namely,  disturbances  of  the  circu- 
lation, particularly  retardation  of  the  current  and  i/ic  j'oniKdiou  of  eddies  lehieh  drirc 
the  blood-}>lates  against  the  vessel-wall;  and  local  changes  in  the  vessel=walls. 
It  is  also  probable  that  thrombosis  is  favored  by  pathological  changes  in  the  blood. 
From  the  variety  of  conditions  under  which  throml)osis  in  man  occurs,  we  must  assmne 
that  at  one  time  one  cause,  at  another  time  another,  jdays  the  chief  part  in  the  forma- 
tion of  the  thrombus,  or  that  all  three  may  take  an  e([ual  i)art  in  the  process. 

If  a  blood-plate  thrombus  or  a  conglutination-thrombus  has  formed  at  any  point, 

coagulation  may  subsequently  occur,  yielding  hbrin-tlucads  which  enclose  a  greater 

or  less  number — often  large  number — of  the  cellular  elements  of    the    blood.     Con- 

ghdination  and  coagulation  may  occur  in  combination ;    and  the  frequency  with  which 

this  comes  to  pass,  judging  from  the  composition  of  the  tliromi)i  occurring  in  man 

(Figs.  16  and  17),  seems  to  denote  the  fact  that  fibrin-ferment  is  produced  during  the 

formation  of  the  blood-plate  thrombus,  and  that  consecjuently,  in  the  neighl)orhood  of 

the  conglutiuated  blood-plates,  processes  of  coagulation  occur  in  the  adjacent  jilasma- 

zone  of  the  blood-stream.     If  white  corpuscles  alone  are  circulating  in   this  zone,  the 

1   mass  of  coagulum  is  white  (Fig.  17)  and  encloses  a  greater  or  less  number  of  red  cells; 

1   if  red  corpuscles  also  circulate  in  the  peripheral   zone,  or  if   the  coagulation  extends 

I   into  the  red  axial  stream,  mixed  thrombi  will  be  formed  (P"ig.  16). 

In  the  place  of  blood-plates  whole  red  blood-cells  may  be  fused  together  by  aggki- 
I  tination  (Fle.rner)  and  so  form  hyaline  thrombus-masses.  If  in  marasmic  individuals, 
I  as  not  infrequently  happens,  or  in  those  who  have  been  subjected  to  some  traumatism, 
i  extensive  thrombosis  occvu-s,  this  occurrence  is  probably  connected  with  a  ferment- 
1  intoxication  {Kohler,  von  Di'iring);  and  the  local  disturbances  of  circulation  only  de- 
1  cide  the  location  of  the  coagulation.  Vaquez  is  of  the  opinion  that  infections  play  a 
[  verj'  prominent  role  in  the  origin  of  cachectic  thrombi.  It  is  probable  that  the  throm- 
bi boses  occurring  in  cases  of  chlorosis  are  dependent  upon  changes  in  the  blood. 

According  to  Xaunyn,  Franken,  Kohler,  Plosz,  Gyorgyai,  Ilanau,  and  others,  a 
more  or  less  extensive  thrombosis  may  be  produced  by  the  injection  into  the  blood- 
vessels of  laked  blood,  solutions  of  htemoglobin,  salts  of  cholic  acid,  ether,  and  other 
I  substances;  yet  the  results  of  thes.^  experiments  are  not  constant  {Schiffer,IIdgyes,Lan- 
j  dois,  Eberth),  and  coagulation  may  not  occur.  The  probability  of  effecting  coagulation 
i  is  proportionate  to  the  degree  of  disturbance  produced  in  the  blood  by  the  substance 
I  injected. 

!  According  to  Arthus  and  Pages,  the  blood  flowing  from  the  veins  becomes  inca- 

I  pable  of  coagulating  spontaneously  if  sodium  oxalate,  sodium  fluoride,  or  soaps  are 
1  added  to  it  in  such  quantities  that  the  mixture  contains  0.07-0.1  per  cent  of  the  oxalate, 
j  or  about  0.2  per  cent  of  the  fluoride,  or  0.5  per  cent  of  soap.  These  salts  all  act  by 
I  precipitating  the  calcium  salts.  If  to  blood,  kept  fluid  by  treatment  with  oxalic  acid, 
I  one-tenth  of  its  volume  of  a  one-per-cent  solution  of  calcium  chloride  is  added,  coagu- 
I  lation  occurs  in  six  to  eight  minutes,  and  the  calcium  salts  pass  into  the  combination  of 
I  the  fibrin-molecule.  The  fibrin-ferment  can  act  upon  the  fibrinogen  only  in  the  pres- 
I  ence  of  calcium  salts.  Under  the  influence  of  the  fil:)rin-ferment,  and  the  presence  of 
!  calcium  salts,  the  fibrinogen  undergoes  a  chemical  change  which  results  in  the  forma- 
1  tion  of  a  calcium-compound,  fibrin.  Hammarsteii,  who  holds  that  the  presence  of  cal- 
j  cium  is  not  necessary  for  the  change  of  fibrinogen  into  fi])rin,  attempts  to  explain  the 
i  observation  of  Arthvs  and  Pages,  through  the  assmnption  that  the  calcium  salts  are 
1  necessary  factors  for  the  conversion  of  prothrombin  into  thrombin. 

1  If  blood  be  allowed  to  flow  beneath  a  layer  of  oil,  into  a  vessel  coated  with  a  fihn 

!  of  vaseline,  it  will  not  coagulate  (Freund);  and  from  this  it  may  be  assumed  that  the 
I  cause  of  the  coagulation  is  to  be  found  in  the  adhesion  of  the  blood  to  a  foreign  body. 
1  Bizzozero,  in  the  year  1882,  described  as  a  new  element  of  the  blood,  small,  flat, 
,  homogeneous  structures,  which  he  designated  as  blood-plates,  and  regarded  as  iilentica! 
;  w-ith  the  hajmatoblasts  described  by  Hayem.  Supported  by  thorough  exi)erimental 
j  investigations,  he  assumed  that  it  was  these  bodies,  which,  in  breaking  up,  induced 
i  coagulation,  and,  therefore,  denied  this  to  be  a  property  of  the  leucocytes. 
'  Since  their  discovery  the  blood-[)lates  have  been  the  object  of  an  extraordinary 

number  of  investigations  and  have  been  intorpret('(l  by  different  writers  in  the  most 
varied  ways.  About  them  revolve  the  disputed  (picstions  as  to  whether  they  are  con- 
stant elements  of  the  blood  or  arise  only  under  patliological  conditions,  whether  they  are 
true  cells  or  represent  only  disintegration  products  of  the  red  or  white  blood -cells,  and 
finally,  whether  they  have  any  definite  relation  to  the  coagulation  of  the  blood.  Rau- 
schenbach,  Heyl,  Weigert,  Lowit,  Eberth,  Schimmelbusch,  II lava,  (Jroth,  Wlassow,  Ziegler, 


142  DISTURBANCES    OF   THE    CIRCULATION. 

Arnold,  Schwalbe,  Deefjen,  Deckhuyzen,  Kopsch,  Argutinski,  Btirker,  and  others  have 
busied  themselves  with  these  questions.  According  to  my  owti  views,  which  agree 
essentiail}'  witli  those  of  Wlassow,  Arnold,  and  Schwalhe,  the  blood-plates  are  for  the 
greater  part  disintegration  and  extrusion  products  of  red  blood-cells;  according  to  the 
investigations  of  Arnold,  Schwalhe,  and  others  similar  products  may  arise  also  from 
the  colorless  cells  of  the  blood.  At  times  they  show  appearances  of  motion;  but  they 
cannot  be  regarded  as  cells.  They  sometimes  contain  within  them  bodies  staining 
similarly  to  nuclear  substance,  and  these  are  probably  to  lie  referred  to  the  elements 
of  nuclear  substance  which  are  present  in  the  red  blood-cells.  According  to  Homer 
Wright  {Virch.  Arch.,  Bd.  186,  1906)  the  blood-plates  are  fragments  of  the  cytoplasm 
of  the  bone-marrow  giant-cells,  and  occur  only  in  those  vertebrates  in  whose  marrow 
giant-cells  are  found.  Their  number  increases  or  diminishes  in  proportion  to  the 
number  of  giant-cells.  Cole  {Johns  Hopkins  Hasp.  Bull.,  1907)  has  produced  a 
specific  agglutinating  serum  for  blood-platelets.  His  experiments  appear  to  speak 
definitely  against  a  genetic  relationship  between  platelets  and  red  blood-cells. 

They  are  found  in  normal  blood,  but  in  great  abundance  only  under  pathological 
conditions.     Without  doubt  they  have  an  important  relation  to  the  coagulation  of  the 
blood.     Barker,  who  does  not  regard  the  blood-plates  as  disintegration  products  of  the    , 
red  blood-cells  but  as  independent  formations,   is   of  the  opinion  that  coagulation  is    ; 
dependent  upon  the  typical  disintegration  of  the  blood-plates,  so  that  the  fibrin-mass 
which  is  ultimately  formed  depends  directly  upon  the  mass  of  disintegrating  blood-plates. 

Morawitz  regards  the  blood-plates  as  independent  cells  {Dcefjcn,  DechJtuijzen,  ; 
Kopsch).  According  to  him,  they  contain  thrombogen  and  thrombokinase,  and  it  is  | 
possible  therefore  to  produce  coagulation  with  the  blood-plates  alone  without  the  ; 
addition  of  leucocytes  or  of  lymph.  Thrombogen  arises  probably  from  the  blood-plates  \ 
alone.  The  white  blood-cells  probably  contain  no  thrombogen,  but  only  thrombokinase,  I 
which  is  probably  produced  by  a  great  variety  of  cells. 

At  the  present  time  no  pathological  significance  can  be  attached  to  an  increase  or 
decrease  in  the  number  of  the  blood-plates.  It  has  been  stated  that  they  are  increased 
in  leukajmia,  afebrile  anajmias,  and  after  haemorrhage,  and  decreased  in  febrile  con- 
ditions and  in  various  intoxications.  The  failure  to  fix  any  definite  normal  standartl 
(their  number  being  estimated  by  various  authors  as  100,000-500,000)  does  not  favor  i 
their  numerical  estimation  as  an  aid  in  diagnosis.  i 

A.  Schmidt,  in  his  work  on  the  blood,  published  in  1892,  in  which  he  collects  the   jSg 
results  of  many  j^ears  of  study  on   the  coagulation  of   the  blood,  regards  the   fibrin- 
ferment  or  thrombin  as  a  cell-derivative,  which  arises  from  an  inactive  antecedent  sub- 
stance, prothrombin,  under  the  influence  of  certain  zymoplastic  substances  which  are  also 


In 

k 


cell-derivatives.     He  likewise  regards  the  fibrinogenic  substance,  or  metaglobulin,  as  a         j^' 
product  of  the  disintegration  of  cellular  protoplasm.     Therefore,  the  substances  causing 
coagulation  as  well  as  those  producing  thrombosis  must  all  be  regarded  as  cell-deriva-      ^ 
tives,  and  the  red  blood-cells  in  particular  are  the  source  of  the  materials  of  coagulation.       i  Jl 

According  to  Pekelharing,  thrombin  is  a  calcium  compound  of  prothrombin  which  \m^ 
arises  from  the  cellular  elements  of  the  blood;  and  coagulation  consists  essentially  in  ; 
the  fact  that  the  thrombin  carries  calcium  over  to  the  fibrinogen,  whereby  the  insoluble  ' 
calcium  compound,  fibrin,  is  formed.  Hammarsten,  on  the  contrary,  is  of  the  opinion 
that  calcium  is  carried  down  with  the  fibrinogen  only  as  a  contamination  and  has  no  signifi-  j 
cance  in  the  change  of  fibrinogen  to  fibrin  in  the  presence  of  thrombin.  According  to  i 
him  the  calcium  salts  are  a  necessary  factor  oidyfor  the  change  ofprufhroi/ihin  into  throinbin.  \ 

Accorduijg  to  Schmiedeberg  and  Ileubner,  there  occurs  in  coagulation  a  hydrolytic  ( 
splitting  of  fibrinogen  into  fibrin  and  fibrin-globulm.  i        j. 

Agglutination-thrombi  occur  in  the  normal   mature  placenta,  and  ^^e  important  ;  \\    J 
pathologically  in  placental    tuberculosis,  a  hyaline  agglutination-thrombus  occurring  '   ■  * 
at  the  site  of  the  primary  lesion  of  the  syncytium   (Warthin,   WoUstcin).     Similar 
thrombi  play  also  an  important  part  in  the  production  of  focal  necroses  (Pcarcc). 

According  to  Corin,  coagidation  occurs  in  the  blood  of  the  cadaver  only  ivhen  the  fer- 
ment was  present  in  the  blood  during  life,  and  the  extent  of  the  coagulation  is  dependent 
directly  upon  the  amount  of  ferment  contained  in  the  blood  during  life.  A  further 
formation  of  ferment  does  not  take  place  after  death,  on  the  other  hand,  it  is  probable 
that  there  is  formed  by  the  vessel-walls  a  body  inhibiting  coagulation.  Between  the 
blood  of  those  dying  suddenly  (strangulation)  and  that  of  individuals  dying  slowly 
there  is  only  a  relative  difference,  depending  upon  tl>e  amount  of  ferment  present.  A 
fluid  condition  of  the  blood  of  the  cadaver  can,  therefore,  be  of  no  significance  in  so  far 
as  the  diagnosis  of  the  manner  of  death  is  concerned.  i  Ju]!^ 

If 

1^ 


THROMBOSIS.  l-l'^ 

Literature. 

{Blood -plates,  Coagulai'on  of  the  Blood,  ond  Tliroiiiho.sis.) 

Arnold:  Freie  Kugelthromben.     Beitr.  v.  Ziegler,  viii.,  1890;  Biologie  der  Blutkorper, 

Virch.  Arch..  145  Bd.,  1896;   Die  Herkunft  der  Blutplattchen.     Cbl.  f.  allfj.  Path., 

viii.,  No.  8,  1897;   Morphologic  der  cxtravasculiiren  Gerinming.    Virch.  Arch.,  150 

Bd.,  1897;    Morphologie  der  intravasc.  Gerinnung.     lb.,  155  Bd.,  1899;    Gerin- 

lumgscentren.  Chi.  Lallg.  Path.,  1899. 
Arthiis:  La  coagulation  du  sang,  Paris,  1899. 
Arthvis  ct  Pages:  Nouvelle  theorie  chimique  de  la  coagulation  tlu  sang.     Arch,  de 

phys.,  ii.,  1890. 
AschoiF  :   Ueber  den  Aufliau  der  menschl.  Thromben.     Virch.  Arch.,  l.'iO  Bd.,  1892. 
Baumgarten :  Ueber  die  neuen  8tandpunkte  in  der  Lehre  von  der  Thrombose.      Berl. 

kliu.  Woch.,  188G;   Blut  in  doppelt  unterbund.  Gefassen.    Verh.  d.  D.  path.  Ges., 

v..  1903. 
Bizzozero:  Blutplattchen   u.   Blutgerinnung.     Cbl.    f.    d.   nied.   Wiss.,    1882,    1883; 

Virch.  Arch.,  90  Bd.;  Arch,  per  le  So.  nied.,  1883;  Arch.  ital.  de  Biol.,  i.,  ii.,  iii.,  iv. 

and  xvi.;  Festschr.  f.  Virchow.     Internat.  Beitr.,  i.,  1891. 
Blum:  Neue  Arbeiten  liber  Blutgerinnung.     Cbl.  f.  allg.  Path.,  1904  (Lit.). 
Bottcher:  Verhalten  d.  Blutes  in  doppelt  unterbund.  Gefassen.     Beitr.  v.  Ziegler,  ii., 

1888. 
Briicke:  Ueber  die  Ursache  der  Gerinnung  des  Blutes.     Virch.  Arch.,  12  Bd.,  1857. 
Biichlers:   Autochthone  Hirnsinusthrombose.     Arch.  f.  Psych.,  15  Bd.,  1893. 
Biirker:   Blutplattchen  u.  Blutgerinnung.     A.  f.  d.  ges.  Phys.,  Bd.  102,  1904. 
Castellino:  Nature  du  zymogene  du  fibrino-ferment.     Arch.  ital.  de  Biol.,  xxiv.,  1895. 
Corin:  Ueber  die  L^rsachen  des  Fliissigbleibens  des  Blutes  bei  der  Erstickung  u.   and. 

Todesarten.     "\'iertcljahrsschr.  f.  ger.  Med.,  v.,  1893. 
Corradi:  Autolyse  u.  Blutgerinnung.     Beitr.  v.  Hofmeister,  i.,  1902. 
Eberth  u.  Schimmelbusch.:  Die  Thrombose  nach  Versuchen  u.  Leichenbefunden, 

.Stuttg.,  LSSS;   Dvskrasie  u.  Thrombose.     Fortschr.  d.  Med.,  vi.,  1888. 
Eisen:  Blood-Plates."'    Journ.  of  Morph.,  xv.,  1899. 

Feldbausch:  Bed.  d.  roth.  Blutkorp.  f.  d.  Gerinnung.     Virch.  Arch.,  155  Bd.,  1899. 
Flexner:  Agglutination  Thrombi.     Univ.  of  Penns.  Med.  Bull.,  1902. 
Freund:  Blutgerinnung.     Limbeck's  Pathologic  des  Blutes,  Jena,  1896. 
Gutschy:  Blutgerinnung  und  Thrombose.     Beitr.  v.  Ziegler,  xxxiv.,  1903. 
Halliburton:  The  Coagulation  of  the  Blood.     British  Med.  Journ.,  1893. 
Hammarsten:  Lehrb.  d.  phys.  Chemie,  Wiesbaden,  1899. 
Hauser:  Beitr.  zur  Lehre  von  der  Fibringerinnimg.     Deut.  Arch.  f.   klin.  Med.,  50 

Bd..  1S92;   Gerinnungscentren.     Virch.  Arch.,  154  Bd.,  1898;  Cbl.  f.  allg.  Path., 

X.,  1S99. 
Hayem:   Du  sang  et  de  ses  alterations  anatomiques,  Paris,  1889. 
Heubner:  Spaltung  des  Fibrinogens.     A.  f.  exp.  Path.,  49  Bd..  1903. 
Hlava:  Bezieh.  d.  Blutplattchen  zur  Gerinnung  u.  Thrombose.    Arch.  f.  exp.  Patk., 

xvi..  1883. 
Lilienfeld:  Blutgerinnung.     Zeitschr.  f.  phys.  Chem.,  xx.,  1894. 
V.  Limbeck:  Klin.  Pathologie  des  Blutes,  Jena,  1896. 
;L6wit:    Blutgerinnung.     Sitzber.  d.  K.  Akad.  d.  Wiss.  in  Wien,  89,  90  Bd.,  1834; 

Blutplattchen  u.  Blutgerinnung.     Fortschr.  d.  Med.,  iii.,  1885;  Die  Beobachtung 

der  Circulation  am  Warmbliiter.     Arch.  f.  exp.  Path.,  xxiii.,  1887;  Blutplattchen 

u.  Thrombose.     lb.,  xxiv.,  1888;  Blutplattchen  u.  Thrombose.    Fortschr.  d.  ^led., 

vi.,  1888;    Bezichung  der  \veis.een  Blutkornerchen  zur  Blutgerinnung.     Beitr.  v. 

Ziegler,  v.,  1889;    Praexistenz  der  Blutplattchen.     Virch.  Arch..  117  Bd.,  1889; 

Cbl.  f.  allg.  Path.,  ii.,  1891;    Studien  zur  Phvsiologie  u.  Patliologie  des  Blutes, 

Jena,  1892. 
jMorawitz:  Blutgerinnung.      D.  Arch.   f.   klin.    Med.,  79    Bd.,   1904;     Vorstufen   v. 

Fibrinfermente.    Fol.  hsem.,  i..  1904. 
Miiller:  Die  morphol.  Veranderung  der  r.  Blutkorperchen.     Beitr.  v.  Ziegler,   xxiii., 

1S9S. 
Pearce:   Experimental  Production  of  Liver-Necroses  by  the  Injection  of  Ilemagglu- 

tinative  Sera.     Jour,  of  Med.  Research,  1906. 
Pekelharing.  Bedeutung  d.   Kalksalze   fiir  die  Gerinnung.     Festschr.   f.    Virchow, 

Berlin,  1891;  Unters.  iib.  das  Fi])rinferment,  Amsterdam,  1892;  Gerinnung.     Deut. 

med.  Woch.,  1892 
Petrone:  Sulla  coagulazione  del  sangue,  Morgagni,  1897. 


144  DISTrRBAXCES    OF   THE    CIRCILATTOX. 

Sacerdotti:  Piastrine  del  sancue.     Arch,  per  le  Sc.  med.,  xiii.,  1893;  Anat.  Anz.,  xvii., 

1900. 
Salvioli:  Comparticipaz.  dei  leucociti  nella  coagulazione.     Arch,  per  le  Sc.  med.,  xix., 

1895. 
Scherer:   Zooid- u.  Oekoidbildung  i.  d.  rothen  Blutkorp.  Zeitschr.  f.  Heilk.,  xvii.,  1896. 
Schmidt,  A. :   Die  Lehre  v.  d.  fermentativen  Gerinnungsercheinimgen,  Dorpat,  1877; 

Zur  Bhitlehre.  Leipzig,  1892;   Weitere  Beitrage  z.  Blutlehre,  Wiesbaden,  1895. 
Schmiedeberg:  ElementarformeneinigerEiweisskorper  (Fibrin).  Arch.  f.  exp.  Path., 

:i[)  Bd.,  1897. 
Schneider:  Bkitplattchengenese.     Virch.  Arch.,  174  Bd.,  1903. 
Schwalbe:  Untersuch.  z.  Blutijerinnung.     Braunschweis,  1901;    Die  Blutplattchen. 

Ergebn.  d.  a.  Path.,  viii.,  1904  (Lit.). 
Vaquez:  De  la  thrombose  cachectique,  Paris,  1890;  Des  coagulat.  sanguines  intra- 

vascul.,  Nancy,  1896. 
Virchow:  Gesamm.  Abhandlungen,  Frankfurt,  1856,  u.  Handb.  d.  spec.  Path.,  i.,  1854. 
Weigert:  Pathol.  Gerinnungsvorgange.     Virch.  Arch.,  79  Bd.,  1880;   Weisser  Throm- 
bus.    Fortsch.  d.  iled.,  v.,  1887. 
Wlassow:  Enters,  (ib.  die  histolog.  Vorgange  bei  der  Gerinnung  u.  der  Thrombose 

mit  besond.  Beriicksicht.  der  Entstehung  der  Blutplattchen.     Beitr.  v,  Ziegler, 

XV..  1894. 
"Wooldridge:  Die  Gerinnimg  des  Blutes,  Leipzig,  1891. 
Wright:  Contr.  to  the  Study  of  the  Coagulation  of  the  Blood.     Journ.  of  Path.,  i., 

1893. 
Zahn:  Thrombose.     Virch.  Arch.,  62  Bd..  1375;  Rippenbildung  an  der  Oberflache  der 

Thromben.  Internat.  Beitr.,  Festschr.  f.  Virchow,  ii.,  Berlin,  1891. 
Zenker:  Intra  vasculare  Fibringerinnung.  Beitr.  v.  Ziegler,  xvii.,  1895, 
Ziegler:  Ueber  den  Bau  der  endocarditischen  Efflorescen.-:en.     Verb.  d.  Congr.  f,  inn. 

.Med.,  vii.,   1888;    Neue  Arbeiten  liber  Blutgerinnuns.      Cbl.  f,  allg.  Path.,  iv., 

1893;   Thrombose.     Eulenburg's  Realencvk.,  xxiv.,  1900  (Lit.), 

See  also  §  39. 

§  ,39.  Thrombosis  occiTrs  most  frequently  in  cases  of  degeneration 
and  inflammation  of  the  intima  of  the  heart  and  of  the  blood-vessels,  as 


.     liG.  iM.— I'olypoid  heart  thrombi  firmly  attached  between  the   trabeculee  of  the  left  ven 
tncie.     o,  Ihrombus  with  smooth  surface;   6,  thrombus  with  G7)en  cavity  of  degeneration.     (Natu- 

r£Ll  SIZG. ) 

well  as  iinder  certain  conditions  which  cause  a  slowing  or  stoppage  of  thi 
circulation — a.s,  for  example,  compression,  narrowing,  or  dilatation  of  th< 
vessels,  fatty  heart,  stenosis  and  insufficiency  of  the  valvular  orifices 
etc.  Perforating  wounds  of  the  vessels,  crushing  of  the  vessel- wall,  an< 
laceration  of  the  intima  lead  likewise  to  the  formation  of  thrombi;  am 
thrombotic  precipitates  are  formed  also  upon  foreign  bodies  lying  in  th 
vessels.     According  to  the  cause  of  the  injury  to  the  vessel- wall  ther 


J 


VARIFTIKS    OF    TlIliOMlU, 


145 


iiKiy  be  distiugiiislied:  traumatic,  infedlon.s,  and  i/imiiic  thrombi,  as  well 
as  \\\or^e  produced  bi/  degenerative  chauges  in  the  vail,  foreif/n  bodies,  and 
tumor  proliferation.  Thrombi  occurring  in  enfeebU'd  in(livi(bials  m  itli 
poor  circulation  (cardiac  Aveakness)  arc  iisually  designated  as  marasmic 
or  cachectic. 

Tliroud)i  maybe  classed  also  according  to  their  relation  to  the  vessel- 
lumen.     Thus  thrombi  attached  to  the  Avail  of  the  heart  (Fig.  21,  a)  or 

blood-vessel  are  knowu  as  parietal 
thrombi,  those  situated  ui)on  the  \alves 
of  the  heart  oi-  veins  (l-'ig.  22,  d)  are 
termed  valvular  thrombi.  In  both 
cases  the  thrombi  may  consist  only  of 
delicate,  translucent,  membranous,  hy- 
aline deposits;  but  are  often  thicker 
and  firmer  and  project  into  the  lumeu 
of  the  heart  or  blood-vessels.  Their 
surface  ofteu  shows  ribbed  elevatious 
which  are  paler  than  the  other  portions. 
A  thrombus  completely  closing  the  Inmen 
of  the  vessel  is  called  au  obturating 
thrombus  (Fig.  22,  a,  b).  The  coagula 
first  formed  are  designated  as  primary 
or  autochthonous,  fhose  subsequently 
deposited  ui)ou  these  as  induced  throm- 
bi. Through  growth  by  accretiou  a  pa- 
rietal thrombus  may  become  chauged  to 
au  obturating  one.  In  this  Avay  it  not 
infrequently  hapjiens  that  upon  au  orig- 
inally white  or  mixed  thrombus  a  red , 
one  (Fig.  22,  c)  is  formed ;  the  throm- 
bosis at  the  begiuuing  occurriug  in  cir- 
culating blood,  while  later,  after  the  clos- 
ing off  of  the  vessel,  the  blood  stands 
still  and  clots  en  masse.  The  re\erse 
may  occur — that  is,  upon  a  thrombus 
originally  red  there  may  be  deposited 
white  or  mixed  coagula — when  a  red 
thrombus  obturating  a  vessel  becomes 
smaller  by  contractiou,  and  thus  o])ens  up 
a  channel  for  the  free  passage  of  blood. 
Thrombi  may  occur  in  any  part  of  the  vascular  system.  In  the  heart 
hey  are  formed  chiefly  in  the  auricular  apj^endages  and  in  the  intertia- 
lecular  spaces,  as  well  as  upon  any  diseased  spot  (Fig.  21,  a)  in  the 
ioart-wall.  They  begin  usually  in  the  deep  recesses  between  the  ti-a- 
kcuhe,  l)ut  through  continual  acci-etions  they  form  larger  masses  of 
ioagula  which  i)rqject  above  the  suilace  in  the  form  of  polypoid  masses 
JFig.  21),  which  ai'e  called  heart=polypi.  They  are  sonuMimes  more  or 
bss  spherical  in  shape,  with  a  broad  l)ase;  at  other  times  they  are  more 
jlub-shaped ;  their  surface  is  ofteu  ril)bed.     In  rare  cases  large  spherical 

i  knobby  thrombi  may  become  loosened ;  and,  in  case  they  cannot  pavSS 
e  ostium,  lie  free  in  the  corresponding  chamber  of  the  lieart.  Sucli 
Be  globular  thrombi  are  sonuitimes  seen  in  tin;  anricles  in  cases  of 
Miosis  and  insnlliciency  of  the  auiicnlo-ventricnlar  oiitices,  bnt  they  are 
rare  occurrence.  After  their  detachment  they  mav  increase  in  size 
10 


Fig.  22— Thrombosis  of  femoral 
aphenous  veins,  a,  /»,  Obturating  mixed 
till  liiininatfd  thrombus ;  c.  red  thrombus 
bowing  peripheral  attachment;  d,  throm- 
us  protmding  from  a  valve.  Clleduced 
ne-fourtb.) 


146 


DISTURBAXCES    OF    THE    CIRCULATIOX. 


through  the  formatiou  of  new  deposits  of  fibrin.  Masses  of  coagula 
wliioli  are  deposited  npon  intlamed  valves  are  kno\m  as  valvular  polypi. 
Parietal  and  vahnlar  polypi  may  become  very  large  and  fill  up  a  large 
part  of  the  lieart-eluDubers. 

In  the  arterial  trunks  thrombi  may  occur  in  a  great  variety  of  places, 
particularly  bcliiud    coustrictious  and    in  dilatations.     Occasioually  in 
cachectic    individuals   with   a   much-degenerated 
arterial  intima,  parietal,  white,  or  mixed  thrombi, 
adherent  to  the  surface,  are  formed  in  the  aorta. 

In  the  veins  thrombi  are  occasionally  formed 
in  the  pockets  of  the  valves  (Fig.  22,  ^7),  from 
which  they  may  gradually  protrude  and  develop 
into  obturating  thrombi.  Often  a  thrombus  may 
grow  from  a  smaller  vein  («),  where  it  was  pri- 
mary, into  the  lumen  of  a  larger  vein  (b).  Thus, 
for  example,  a  thrombus  having  its  origin  in  a 
small  vein  of  the  lower  extremities  may  finally 
grow  into  the  inferior  vena  cava  and  even  reach 
the  heart.  Of  especial  importance,  because  of 
the  resulting  local  disturbances,  are  the  obturat- 
ing thrombi  of  the  femoral  veins,  the  renal  A'eins, 
the  sinus  of  the  dura  mater,  the  ven®  cavse,  and 
the  portal  veins. 

Thrombosis  in  the  smallest  vessels  is  most 
frequently  the  result  of  disease  of  the  surround- 
ing tissues,  particularly  infectious  and  toxic  in- 
flammations and  necrotic  processes.  The  throm- 
bi formed  are,  for  the  greater  part,  hyaline;  ii 
their  composition  the  colorless  elements  of  the  red 
blood-corpuscles  have  the  chief  share,  fusing  to- 
gether into  a  homogeneous  mass.  Nevertheless, 
it  may  be  demonstrated  occasionally,  by  means 
of  proper  technique  (Weigerfs  staining  method), 
that  they  also  contain  thready  fibrin.  Thrombi 
of  smaller  vessels  occur  also  after  burns  of  the  skin 
(Klebs,  Welti,  Silbermann)  and  often  in  cases  of 
poisoning — for  examx)le,  with  corrosive  sublimate 
(Kaufmann) — and  are  found  especially  in  the 
smaller  vessels  of  the  lung.  They  frequently 
occur    in    ha'morrhagic    infarcts    (Fig.    13,    a,). 

Thrombi  originating  in  the  capillaries  may  develop  also  into  the  efferen 
veins,  ])artly  for  the  reason  that  through  the  obturation  of  numeroii 
capillaiies  the  blood  flows  more  slowly  into  the  veins,  partly  also  fo 
the  reason  that  disintegrating  red  cells  and  blood-plates  pass  into  th 
veins  in  hirge  numbers.  ; 

The  first  deposits  in  the  formation  of  a  parietal  thionibus  consist  o' 
delicate,  translucent,  or  whitish  layers.  The  fully  formed  thrombus  i 
a  rather  firm,  dry  mass,  firmly  adherent  to  the  inner  surface  of  the  ve; 
sel  or  heart,  and  in  color  and  structure  vaiyiug  according  to  the  coi 
ditions  mentioned  above.  Thrombi,  oi'iginally  soft  and  moist,  underg 
in  time  a  process  of  contraction,  and  thereby  become  firmer  and  moi 
dry.  By  means  of  such  contraction  vessels  closed  by  obturating  throml 
may  again  become  opened  for  the  passage  of  the  blood.  : 


Fig.  23.  —  Remains  of  : 
thrombus  of  the  rjcrht  femora, 
vein  occurring  three  yearj 
before  death,  a.  Obliterate'! 
portion  of  the  vein  (the  righ; 
common  iliac  artery  was  als' 
obliterated);  h,  c,  d,  connei 
tive-tissue  cords  in  the  Iv 
mina  of  the  vein  and  it. 
branches;  e,  fresh  thrombu;' 
(Natural  size.) 


I 


SEQUF.L.E    OF   THROMBOSIS. 


147 


Tu  case  of  iiiarkod  contraction,  the  fibrin,   blood-plates,   and  the  rod 
blood-cells  may  become  chanaeil  into  a  linn  mass,  a\  liicli  may  remain  in 


0., 


^ 


^^ 


^ 


—  ^ 

J 


/ 


^"^r^^ 


Fig.  24.— Obliteration  of  a  pulmonary  artery  by  connective  tissue  after  embolic  plugging  of  its  lumen. 
(MfUler's  fluid,  hapmatoxylin.  andeosin.)  a,  Artery  wall;  fo,  connective  tissue  Ulling  tbe  vessel-lumen; 
c,  d,  newly  formed  blood-vessels.    X  45. 


this  condition  for  a  long  time,  become  firmly  adherent  to  the  yessel-wall, 

and  finally  nudergo    calcification.      This  may  occur  in   both  Aah  iilar 

heart-thrombi  and  thrombi  located  in  the  yessels.     The  chalky  concic- 

!  tious  formed  in  this  manner  in  the  yeins  are  known  as  phleboliths ; 

j  those  occurring  more  rarely  in  the  arteries  as  arterioliths. 

Contraction  and  calcification  are  relatiyely  fayorable  sequela?  of 
\  thrombosis.  Much  less  fayorable  are  the  more  frequent  i)rocesses  of  de- 
i  generation  occurring  in  thrombi,  which  are  known  as  simple  and  as  jjuri- 

form  or  yellow  septic  softening.  In 
simple  softening  the  central  portion  of 
the  thrombus  becomes  changed  into  a 
grayish-red,  or  gray,  or  grayish -wliite 
grumous  mass,  consisting  of  disinte- 
grated and  shrunken  red  corpuscles, 
pigment-granules,  and  colorless,  gian- 
ular  debiis.  If  the  softening  extends 
to  the  superficial  layers,  and  if  there  is 
at  the  same  time  a  certain  strength  of 
blood-current  in  the  neighl)orliood  of 
the  thrombus,  the  products  of  disin- 
tegration may  b(^  sw<'i)t  along  into  the 
circulation.  If  th('r('l)y  larg<'r  ])i«'ccs 
become  loosened  and  ti'ans]>orted  l)y 
the  blood-stream,  artei-ial  em])oli  will 
be  produced  (sec  Fig.  2). 

In  tlw  yellow  puriform  oi-  septic 
softening  the  throml)iis  br<'aks  down 
into  a  yellow,  or  grayish-yellow,  or 
reddish -yellow,  pus-like,  grumons,  creamy,  and  at  times  foul-smelling 
ma.ss,  consisting  of  pus-corpuscles  and  a  large  amount  of  iincly-granular 
>u])stance,  comjjosed  of  fatty  and  albuminous  detritus  and  micrococci. 


I  Fig.  25.— Remains  of  embolic  plugs  In  a 
branch  of  the  pulmonarv  artery,  a,  Con- 
1  tracted  embolus  traversed  by  connective-tissue 
Ithreads;  ?>,  cords  of  connective-tissue  crossing 
jtlie  oriflces  of  branch  vessels.     (Natural  size.) 


148  niSTURBAXCES    OF    THE    CIRCULATION. 

This  mass  acts  as  a  destructive  irritant  upon  tbe  surronuding  tissues, 
giving  rise  to  iullammation.  As  a  result  the  iutima  becomes  cloudy,  and 
there  arises  a  purulent  inflammation  in  the  media  and  adventitia,  as 
well  as  in  the  tissues  about  the  vessel.  After  a  short  time  all  the  vascu- 
lar coats  become  infiltrated  and  present  a  dirty-yellow  or  grayish-yellow 
appearance.  A  suppurative  destruction  of  the  tissues  finally  results. 
If  puriform  masses  are  transported  by  the  blood-stream  to  other  parts 
of  the  vascular  system,  thej'  will  give  rise  to  metastatic  foci  of  necrosis 
and  septic  disintegration  of  the  tissues,  and  purulent  inflammation,  iu- 
A^olving  not  only  the  vessel-wall  but  also  the  neighboring  tissues. 

The  ijrocess  of  puriform  softening  of  a  venous  or  arterial  thrombus, 
associated  with  a  purulent  infiltration  of  the  vessel-wall,  is  designated 
thrombophlebitis  purulenta  or  thrombo=arteritis  purulenta.  The  in- 
flammation of  the  vessel-wall  may  take  its  start  either  in  the  softening 
thrombus  or  in  the  tissues  adjacent  to  the  vessel.     In  the  latter  case  the 


tlSuTljIi!^- 


^?^c 


dl^r 


':J--^fl 


Fi(.    ■>(.  -I  Ml)    ii-ii      f    in  iiiKviiiui   uteiy,  with  siippuiativc  .iiteiitis   embolic  aneurism,  and  peri-l^,- 
arif  nil   rm  i  i  i  n  i      i  (  \  Id  ii  1   fiu  hsm  )    a,  b,  c,  (/,  t.  Layers  of  the  mttstinal  wall ,  f,  artery  waUjjM  Mi: 

y^'^"";"'"'^  ^  ,",  "   '     y  '  "'^     ''"'^  ''^  .Mi-'.iiili(  (li  11  .1  lit. IV  wliiO)  Npaitlv  (UstioM-ubysiippura-jH 
blood''-  "  '    '"""""^1  I""i""i '""I"  "1  ""i  11"    MilmiiKuM,/,  V.  IMS  gorged  with- ^ 


softening  of  the  tlirombus  is  coincident  with  the  inflammation  of  the  vc. 
sel-wall  or  else  follows  it.     These  processes  occur  most  frequently  in  thd!  i 
neiglihorliood  of  purulent  foci.  ' 

'ihc  most  favorabhi  secfuola  of  thrombosis  is  the  organization  of  th«i 
thrombus— tliat  is,  a  substitution  of  the  thrombus  by  vascularizet' 
connective  tissue. 

Tlie  new  connective  tissue  develops  from  the  proliferating  cells  of  tb' 
vessel-wall,  and  all  the  coats  of  the  vessel  may  take  part  in  the  proliferi  (j||^i=* 
ation.  The  tlirombus  itself  takes  no  part  in  the  organization;  it  is  i\  .Jif. 
dead  mass  which  excites  inflammation  in  the  surrounding  tissues.  I';|Ii<Ei' 
the  course  of  lime  the  dead  thromluis-mass  is  replaced  by  vascuIarize(i|JWi 
connective  tissue   (Fig,  24,  h,  c,  d). 


SEQI  EL.K    OF   THROMBOSIS.  149 

The  C'icatrieial  tissue  formed  in  tlie  place  of  the  thrombus  ('iHilracls 
more  or  less  in  the  course  of  time.  The  cicatrices  fornu'd  after  lipUiou 
may  thus  become  very  small.  Such  a  cicatrix  in  tlie  continuity  of  a  ves- 
sel may  later  appear  simply  as  a  thickeniiio- of  the  vessel -Avail,  or  there 
may  remain  only  threads  and  trabecuhe  (Fi^.  ^o,  />,  c,  d),  -wliich  cross 
the  lumen  of  the  thrombosed  vessel,  so  that  the  blood-stream  can  once 
more  pass  the  alfected  spot.  Not  iiifre(inently  the  connect i\e-t issue 
strands  crossing  the  vessel  cause  a  maikeil  narrowing  of  the  lumen;  or 
the  vessel  may  become  completely  obliterated  (Fig.  2.%  a),  so  that  the 
vessel  for  a  gi-eater  or  less  distance  becomes  converted  into  a  solid  tibrous 
cord. 

The  pieces  broken  loose  from  a  thrombus  and  carried  into  an  artery 
and  there  lodged — that  is,  emboli — generally  induce  new  dei)osits  of 
tibrin  upon  their  surface.  Later  they  undergo  the  same  changes  as 
thrombi,  and  may  either  soften,  or  contract^  (Fig.  25,  a),  or  become  calci- 
fied. If  the  emboli  are  non-infective  they  usually  become  replaced  by 
vascular  connective  tissue  (Fig.  24,  b,  c). 

In  many  cases  the  new-formation  of  connective  tissue  leads  to  the  ob- 
literation of  the  artery  (Fig.  24).  In  other  cases  in  the  place  of  the  em- 
bolus there  is  developed  only  a  ridge  of  connective  tissue  or  a  nodular  or 
flat  thickening  of  the  intima.  In  still  other  cases  the  lumen  of  the  vessel 
is  traversed  by  strands  of  connective  tissue  (Fig.  2;"),  h),  which  either  run 
separately  or,  interlacing,  form  a  fine-  or  coarse-meshed  network. 

If  pyogenic  organisms  are  present  in  the  emboli,  as  is  very  likely  to 
be  the  case  when  the  emboli  arise  from  a  thrombus  lying  in  a  suppurat- 
ing focus,  there  is  produced  a  purulent  process  (Fig.  26,  i)  at  the  site  of 
the  embolus  (Fig.  26,  g),  and  occasionally  ulceration  also. 


Literature. 

(Thro)nhosls.') 

Apollonio:  Organisation  des  Unterbindun|i;stlirombus.     Beitr.  v.  Zicgler,  iii.,  1888. 

Arnold:    Die  Oeschicke  d.  Leukocyten  bei  der  FrenidkOrperenibolio.     Vircb.  Arch., 
V.V.)  Bd.,  1893. 

Baumgarten :  Die  soi<:.  OrsjanLsation  des  Thrombus,  Leipzig,  1877. 

Bubnoff:   L'eber  die  (Jiganisatiou  des  Tiirombus.     Virch.  Arch.,  44  Bd.,  1808. 

Biichlers:  Autochthoiie  Hirnsinusthroinbose.     Arch.  f.  Phys.,  25  Bd.,  1893. 

Flexner:  Ai^^u-hilination  Thrombi.     Jour,  of  Med.  Ilesearch.  1902. 

Herz:  reher  altere  Thrombeu  im  Herzen.     Deut.  Arch.  f.  klin.  Med.,  37  Bd.,  1885. 
;  Heuking  u.  Thoma:    Susbtitut.  d.  marant.  Thrombus  durch  Bindegevvebe.     Virch. 

Arcli.,  1U9  lid.,  1887. 
I  Justi:  Hyaline  Capillarthrombose.     luaug. -Diss.,  Marburg,  1894. 

Lubnitzky:  Die  Zusammensetzung  des  Thrombus  in  Arterienwuuden.     luuug.-Diss., 
Bonn,  1885. 

Osier:  Trans,  of  Assn.  Amer.  Phys.,  1887. 

Pernice:  Sulla  fusione  purulenta  del  trombo.     Sicilia  !Med.,  i.,  Palermo,  1889. 

Pick:  Hyaline  Thrombose.     Virch.  Arch.,  138  Bd.,  1894. 

Raab:    Anat.  Vorgiinge  nach  Unterbindung  der  Blutgefasse.     Virch.  Arch.,  75  Bd., 
!  1ST9. 

■  V.  Recklinghausen:  Fnie  Kuirdthromben.     Deut.  Arch.  f.  klin.  Med.,  37  Bd.,  188.5. 

Schweizer:  Tlnomliose  bei  Cliloiose.     Virch.  Arch.,  152  Bd.,  1898. 

Stange:  Kugeitiironilius  iiu  Vorliof.     Arb.  a.  d.  path.  Inst,  zu  Giittingen,  1889. 

Vaquez:  l)e  la  thrombose  cachectique,  Paris,  1890. 

Virchow:  Thrombose  und  Embolic,  Ges.  Abhandl.,  Frankfurt,  1850. 

Volker:  Varix  d.  Vena  facialis  ant.  mit  zwei  Venensteiuen.     Deut.  Zeitschr.  f.  (^liir., 
28  Bd. 

Watson:  Boston  Med.  and  Surg.  .Jour.,  1894. 


150 


DISTURBANCES    OF   THE    CIRCULATION. 


Welch:  Tlironibosis  and  Embolism.     Allbutt's  System  of  Medicine,  1899  (Lit.). 
Welch  and  Flexner:  Jour,  of  E.xper.  Med.,  1896. 
See  also  ^  38. 

§  40.  As  stasis  or  stagnation  of  the  blood  is  designated  a  stoppage 
of  the  cirenhition  without  coagulation,  in  which  condition  the  red  blood- 
cells  are  so  closely  pressed  together  that  the  small  vessels  appear  filled 


Fig.  27.— Congestive  stasis  in  the  vessels  of  the  corium  and  papillae  of  the  plantar  surfaces  of  the 
toes  from  a  man  dying  of  valvular  disease,  heart  failure,  and  arteriosclerosis.  (Miiller's  fluid,  alum  car- 
mine.)   Toes  presented  a  deep  violet  color,  and  beginning  gangrene.    X  20. 


i.Jh 


with  a  red  mass  of  blood,  in  which  the  outlines  of  the  individual  red 
blood-cells  cannot  be  distinguished  (Fig.  27).     The  cause  of  this  coudi-  | 
tioM  lies  most  frequently  in  the  occurrence  of  a  jnarked passive  congestion.  \ 
When  the  blood  entering  into  a  certain  tissue-area  finds  no  avenue  of  | 
exit,  the  circulation  in  the  small  veins  and  capillaries,  and  even  in  the  : 
smallest  afferent  arterial  branches,    comes    to  a  permanent  standstill.  * 
Since  from  the  arteries  there  come  with  every  pulse -wave  fresh  masses  of  I 
blood  to  tlu;  congested  area,  the  caj)illaries  and  veins  become  more  and  ; 
more  distended  and  the  i)ressure  within  these  rises  to  the  height  of  that 
at  the  point  of  divergence  of  the  nearest  permeable  artery.     In  this  way 
a  large  portion  of  the  fluids  of  the  blood  are  pressed  out  of  the  capillaries  ; 
and  veins,  and  as  a  result  of  this  the  red  blood-cells  become  so  closely  ; 
packed  together  that  their  contours  are  no  longer  distinguishable,  and 
the  total  contents  of  the  vessel  form  a  homogeneous,  scarlet-red  column  , 


STASIS  :     O.DEMA .  151 

(Fip:.  27).  The  red  blood-cells,  however,  are  not  fused  together ;  as  soon 
as  the  hindrance  to  the  outtlow  is  removed  and  the  circulation  I'estoicd, 
the  individual  corpuscles  become  once  more  sciiaiated  from  one  anotlu'r. 
Stasis  may  be  caused  by  many  injurious  inllucnccs  which  alfcct  the 
vessel-wall  and  the  lilood  itself.  Thus,  for  example,  luat  and  cold,  irri- 
tation irifh  acids  and  alLalirs,  action  of  concod rated  .solutions  of  sugar  and  salt, 
action  of  cldoroform,  alcoliol,  etc.,  cause  stasis.  These  injuiious  agents  act 
in  the  iiist  place  by  abstracting  Mater  from  the  blood  and  vessel-walls, 
and  fuither  by  producing  essential  changes  in  the  composition  of  the 
blood -corpuscles,  blood-plasma,  and  vessel-walls;  so  that  the  red  cells 
become  less  mobile  and  the  vessel- walls  come  to  offer  increased  fiictional 
resistance  to  the  blood-stream,  and  at  the  same  time  to  permit  the  tluid 
portions  of  the  blood  to  pass  through  them  the  more  readily.  Stasis 
may  also  be  produced  by  loss  of  water  and  drying  of  the  tissues,  an  event 
Avhich  may  occur,  for  example,  in  injuries  which  lay  bare  tissues  lying 
within  the  bodj'  (intestine). 

Literature. 

(Stasis. ) 

Cohnheim:  Vnrlesungen  liber  allgcMiieine  Pathologic,  Berlin,  1882. 
V.  Recklinghausen:  Allgem.  Pathologie  d.  Kreislaul's  u.  d.  Ernahrung,  Stuttgart, 
1S«3. 

IV.  (Edema. 

§  41.  The  free  fluid  which  permeates  the  tissues  is  essentially  a  tran- 
sudate from  the  blood,  though  under  certain  conditions  a  portion  of  the 
tissue-fluids  contained  in  the  cells  and  fibres  may  also  pass  over  into  the 
free  lymph.  The  passage  of  fluid  from  the  vessels  is  in  pai-t  a  process  of 
nitration  and  in  j^art  is  to  be  regarded  as  of  the  natuie  of  a  secretion, 
accomplished  by  means  of  a  specific  function  of  the  capillary  walls. 
The  fluid  secreted  by  the  capillaries  mingles  with  the  products  of  metabo- 
lism in  the  tissues,  and  is  taken  up  from  the  tissue-sj>aces  l)y  means  of 
the  lym])h-vessels,  and  through  the  thoracic  duct  is  again  returned  to  the 
ivenous  blood. 

!  E\ery  increase  in  the  transudation  of  the  fluids  of  the  blood  causes 
Ifirst  a  more  marked  saturation  of  the  tissues,  which  may  be  compensated 
|for  by  an  increased  absorption  through  the  lymph-vessels.  This  com- 
pensation has,  however,  its  limits;  with  increased  transudation  from  the 
blood-vessels  there  is  produced  a  more  or  less  pei-manent  over-saturation 
of  the  tissues  with  the  transuded  fluids. 

'  The  condition  which  is  ])roduced  by  this  collection  of  fluids  in  the  tis- 
l^ues  is  known  as  dropsy,  oedema,  or  hydrops.  According  to  the  extent 
ir>f  the  condition  there  may  be  distinguished  a  r/cncral  and  a  localized  Jn/- 
th'ops.  An  (cdema  extending  o\ ci-  the  supei'ticial  portions  of  the  body  is 
{known  as  anasarca  or  hyposarca. 

1  The  transudate  from  tlie  blood  irhic/i  connf  Hides  the  adenxt  or  the  lii/drops 
\'s  always  much  jmorcr  in  albumin  than  the  blood-i)lasiiia.  The  fluid  colU'cls 
;\t  first  in  the  tissue-spaces  as //•ee/mw/'-/////r7  ])ushiug  apart  the  tissue- 
;ilements  (Fig.  28,  h),  but  may  also  soak  into  the  tissue-elements  themselves 

md  cause  a  swelling  of  the  cells  and  fibres,  and.  under  ceitain  condil  ions, 

he  formation  of  vacuoles  (Fig.  29),  due  to  the  collection  of  drops  of 

luid  in  the  cells  or  their  derivatives. 

This  may  be  most  frequently  dononstrated  in  the  epithelium  of  the 

)ody-surfaces  and  of  glands,  but  beconu'S  at  times  distinctiv  evident  in 


152 


DISTURBAXCES    OF   THE    CIRCULATIOX. 


otlier  tissue-elements — for  example,  iu  eonuective-tissue  cells  and  muscle- 
fibres  (Figs.  29  and  30),  whose  fibrillse  become  pushed  apart  by  drops  of 
fluid.     Moreover,  it  often  happens  in  oedematous  tissues  that  cells  be- 


b-yj- 


/ 


^s^t^^ 


^^0 


-^^--i^-^^ 


Fig.  28. — Stasis-oedema  of  the  papillary  bodies  of  the  skin  of  the  leg  from  a  case  of  mitral 
stenosis.  (K.  Ziegler,  1.  c).  a.  Lymphocytes;  6,  connective  tissue  fibrillar  with  cells;  c,  red  blood- 
cells;  d,  blood-vessel.     X  300.  ffl  11 

come  loosened  from  their  basement-membrane,  jjarticularly  in  the  lungs 
and  serous  membranes,  where  the  epithelial  cells  iu  large  numl)er  may  ; 
be  mixed  Mith  the  fluid.     In  cedema of  the  skin,  the  epidermis  (Fig.  31) 

may  be  separated  and  lifted 
up  from  the  papillary  bod- , 
ies,  while  at  the  same  time  • 
the  fibrillte  of  the  latter  are* 
pushed  apart. 

Tissues  which  are  the 
/  seat  of  oedema  appear  swol- 
len, though  the  degree  of 
swelling  depends  essentially, 
upon  the  structure  of  thej 
affected  tissue.  The  skin' 
and  the  subcutaneous  tis- 
sue are  able  to  take  up  into 
their  lynii)h  -  spaces  large 
cpiantities  of  fluid,  so  that 
an  extremity  may  become 
enormously  swollen  tlircnigli 
cedema.  In  this  conditioii 
it  is  pale,  possesses  a  doughj 
consistence,  and  pits  oi 
pressure.      On   incision  ai 


Fig.  29.— Hvdropic  connective-tissue  cells  from  the 
subcutaneous  tissue  of  a  case  of  chronic  cedema  due  to 
stasis.     (K.  Ziegler,  1.  c).     X  400. 


I 


a<:DEMA. 


]53 


abuiuliinco  of  clear  fluid  escapes,  sliowinj;-  llic  tissues  lo  be  tii()i(>uj;lily 
saturated  Avitli  lluid. 

Tlie  luui;'  behaves  in  a  similar  way.  Owinj;-  to  its  limited  space  it 
cannot  l)ecome  i;reatly  distended,  but  it  contains  great  numbers  of  cavi- 
ties tiile(l  witii   air,   Avhich,    in   tiie 


ad\eiil  til'  (edema,  become  tilled 
with  lluid,  which  on  i)ressuio 
escapes  from  the  cut  suiface,  gen- 
erally mingled  with  air-bubbles. 

(Edematous  swellings  of  the 
kidney,  which  may  become  very 
marked,  are  caused  especially  by 
the  retention  in  the  dilated  urin- 
ary tubules  of  the  water  of  the 
urine  secreted  by  the  glomeruli. 
In  the  connective  tissue  between  the  tubules  lai 
lect  but  rarely. 

The  amount  of  blood  contained  in  cedematous  tissues  is  variabh 
their  color  varies  accordingly. 

]>ody-cavities  which  are  the  seat  of  a  dropsical  etfusiou  contain  at  one 
time  a  large,  at  another  time  onlv  a  small  amount  of  a  clear,  usually 


iijrituiliiial  section  of  cedematous 
niuscle-llbrcs  from  the  ralf  muscles  in  a  case  of 
chronic  u'dcina  of  the  lesrs.  (FlemmiuR's  solution, 
safniuin.)     x  4."). 


amounts  of  fluid  col- 
and 


7     J%>  A 


OL  i' 


the  papillary  boiiies 
Ziegler,  1.  c).     a,  Coi 


y  (iMl.'iTiii  ol  I  ill-  i.apiilaiy  Ijodi 
I  inliammatory  exiuiat.',  from 
b,  exudate  consisting  of  fluid, 


^s,  witli  elevation  of  the  epidermis  from 
a  case  of  phlegmon  of  the  ihijjli.  (K. 
fibrin    and    Uucocytcs.      X    40. 


light-yellow,  rai'cly  quite  colorless,  alkaline  fluid,  which  at  times  eon- 
tains  a  few  fibrin  flakes  (see  the  chai)ter  on  Inilammatioii )  <  'unipicss- 
ible  oi'gans  ai-e  com])ressed  by  the  effnsion  ;  the  body-cavities  are  dilated. 

A  collection  of  fluid  in  the  abdominal  cavity  is  knctwn  as  ascites. 

The  albumin-content  of  jiure  transudat<'S  is  not  tlu^  same  in  all  the 
body-ca\  ities  and  tissues,  but  differs  in  a  pronouiKM'd  degivc.  Accoi-d- 
ing  to  Iteuss,  the  albumin-content  of  transudations  of  the  pleui'a  is  L'L*..~) 
\})ro  mit/c;  that  of  the  i>eiicardiiim,  IS..'};  of  the  ])eritoneum,  11. 1;  of 
the  sidjcutaneous  connective-tissiu',  5.S;  of  the  cavities  of  the  brain  and 
ppinal  cord,  1.4.  These  facts  may  be  taken  as  a  proof  of  the  dilfe rent 
ponstitution  of  the  vessel-walls  in  the  various  tissues  of  the  body, 

Tlie  water  of  tlie  organs  and  tissues,  according  to  Ilctdenhatii,  ("  Versiiclu!  und  Frii- 
;i  n  zur  Lehre  von  der  Lyniplibildung,"  Arch.  f.  d.  (jes.  Phys.,  49  Bd.,  1891,  and  Vcrh. 


154  DISTURBAXCES    OF   THE    CIRCULATIOX. 

des  X.  iuteruat.  med.  Cong.,  ii.,  Berlin,  1891)  consists  of  three  parts — the  water  of  the 
blood  present,  the  lymph  of  the  organ  under  consideration,  and  the  water  contained  in 
the  cells  and  fibres — the  tissue-water.  Under  certain  conditions  the  last-mentioned 
may  undergo  considerable  variation,  and  can  increase  at  the  expense  of  the  free  water 
of  the  blood  or  lymph,  or  diminish  in  their  favor. 

If  the  proportion  of  crystalloid  substances  (urea,  sugar,  salts)  in  the  blood  be  in- 
creased, both  the  blood  and  lymph  become  at  the  same  time  richer  in  water;  and  this 
is  possible  only  in  tiiat  the  substances  injected  into  the  blood  pass  into  the  lymphatics, 
and,  by  their  affinity  for  the  tissue-watei',  excite  a  passage  of  water  from  the  tissue- 
elements.  The  rapid  passage  of  the  crystalloid  substances  from  the  blood  into  the 
lymph  is  accomplisiied  with  the  aid  of  a  force  inherent  in  the  capillary  cells,  and  is  not 
a  simple  diffusion-phenomenon.  This  is  evident  by  the  fact  that  the  content  of  tlie 
lymph  in  sugar  or  salts  is  often  greater  than  that  of  the  blood. 

v:^  42.  According  to  theii  etiology  we  may  distinguish  five  varieties 
of  oedema  :  cedemn,  dne  to  cnierial  cojigesUon ;  oedema />-om  siaynatlon  of 
the  blood ;  aHlema  caused  by  a  hindrance  to  the  outflow  of  the  lymph;  cedema 
caused  by  disturbance  of  the  capillary  secretion  due  to  cluinges  in  tlie  capil- 
lary walls ;  and  adema  ex  vacuo.  The  fourth  one  of  these  varieties  is 
designated  by  the  practising  physician  as  inflammatory,  hydrremic  or 
cachectic,  or  neuropathic  oedema,  according  to  the  clinical  features  of 
the  case. 

(Edema  due  to  arterial  congestion  occurs  acutely  in  localized  areas, 
in  the  skin  and  subcutaneous  tissue,  mucous  membranes,  larynx,  bronchi 
(asthma),  nose,  periosteum,  and  muscles  (fleeting  rheumatic  pains),  and 
has  usually  a  neurotic  character.  In  individuals  showing  the  tendency  in 
a  mai-ked  degree,  bulla;  may  even  l>e  formed  in  the  skin. 

CEdema  due  to  stagnation  of  tlie  blood  arises  when,  as  a  residt  of 
the  marked  hindrance  to  the  outflow  of  blood  from  the  capillaries,  the 
pressure  in  the  capillaries  rises  and  the  fluid  portion  of  the  blood  seeks 
a  lateral  outlet,  so  that  an  increased  amount  of  fluid  escapes  from  the  ves- 
sels. The  amount  of  the  escaped  fluid  is  the  larger  the  greater  the  de- 
gree of  discrepancy  between  inflow  and  outflow;  it  is  therefore  increased 
through  a  coincident  increase  of  the  blood  inflow. 

The  escaping  fluid  is  always  poor  in  albumin,  but  with  increased 
])ressure  in  the  veins  the  albumin-content  is  increased  (Senator) ;  the 
fluid  contains  lymphocytes  (K.  Ziegler)  and  red  blood-cells,  the  lutmber 
being  increased  in  proportion  to  the  degree  of  stagnation. 

Tlie  immediate  result  of  an  increased  transudation  from  the  blood- 
vessels is  au  increase  in  the  lymph-flow,  and  this  may  be  sufficient  to 
carry  off  all  the  fluid.  If  it  does  not  so  stiflice,  the  fluid  collects  in  the 
tissue-spaces  and  there  results  the  condition  of  stagnation-a'dema  or 
dropsy.  According  to  Lauderer,  this  occurrence  is  favoiod  ('Specially  by 
the  fact  that  the  elasticity  of  the  tissues  becomes  diminished  as  the  result 
of  the  long-continued  increase  of  the  pressure  to  which  they  are  sub- 
jected. In  chronic  oedema  of  long  standing  the  lymifliocytes  in  part 
ujidcrgo  progressive  changes  and  are  transformed  into  the  cells  known 
as  klasmatocytes,  plasma-cells,  and  mast-cells  (K.  Ziegler). 

Obstruction  to  the  outflow  of  lymph,  as  experiments  in  this  direc- 
lion  lia\«'  slmwu.  is  not  ordinarily  followed  by  oedema.  The  lymph- 
ve.s.sels  in  tlic  different  regions  of  the  body  possess  such  extensive  anas- 
tomoses lliat  an  (d»s1  nid  ion  1o  the  outflow  of  lymph  does  not  readily  occur. 
Even  when  all  of  the  lyini)h-channels  of  an  extremity  are  obstructed,  if 
the  amount  of  lymph  formed  is  normal  there  results  no  oedema,  inas- 
mucli  as  the  l)lood-vesst'ls  are  able  to  take  up  the  lymph  again.  Only  the 
occlusion  of  the  thoracic  duct  is  likely  to  lead  to  a  stagnation  of  the  lymph 


i 


CEDE^IA.  155 

ami  the  production  of  oedenui,  particularly  of  ascites,  but  it  must  be 
observed  that  even  in  this  case  collateral  channels  may  i)e  opened  up  and 
suflice  to  carry  otf  the  lymph. 

Although  lymphatic  obstruction  is  not  ordinarily  sullicicnt  in  itself 
to  i)i'odu('e  (edema,  yet  it  does  increase  an  cedema  cansed  by  an  increased 
transndation  from  the  blood-vessels. 

Pathological  changes  in  the  walls  of  the  capillaries  and  veins  of 
such  a  nature  as  to  cause  an  increase  in  the  vascular  secretion,  and 
tliereby  give  rise  to  an  oedema,  may  occn I-  as  the  icsult  of  a  lonfi-con- 
tiiu«'dj)a.s.sin'  com/estion  and  the  conseipient  imperfect  renewal  of  the  l>lood. 
Such  changes  occur,  liowever,  much  more  freijuently  as  the  result  of 
l)rolonged  IsclHrmia,  lack  of  oxyf/en,  action  of  h'ujh  or  low  temperatures^  trau- 
matic lujunj,  the  it<'veJopment  of  tumors  (especially  in  the  serous  mem- 
branes), htj'cction,  and  intoxication.  It  is  also  probable  that  either  Irrita- 
tion or  parali/sls  of  the  vasomotor  nerves  may  lead  to  an  increase  of  the 
vascular  secietion.  Just  what  changes  the  vessels  suffer  imder  these  con- 
ditions we  are  not  able  to  state  precisely,  but  it  may  be  assumed  that 
some  alteration  of  the  endothelial  cells  and  of  the  cement-substance  plays 
i  the  chief  role  rendering  the  vessels  more  permeable.  The  cedemas  pro- 
i  duced  by  the  influences  above  mentioned  may  be  classed  according  to 
their  cause  as  toxic,  infectious,  thermal,  traumatic,  ischaemic,  neuro- 
pathic, etc.  ;  and  such  a  classilication  has  much  to  commend  it.  Hith- 
erto the  forms  of  anlema  here  under  consideration,  with  the  exception  of 
the  neuropathic  forms,  have  been  classed  ordinarily  into  two  groups — 
i  namely,  inflammatory  and  cachectic  oedema. 

j  Inflammatory  oedema  is  without  doubt  to  be  referred  to  an  altera- 
tion of  the  vessel-wall,  and  occurs  both  as  an  independent  affection,  in 
the  form  of  circumscribed  or  more  diffuse  swellings  and  hydroi)ic  effu- 
sions, and  also  as  a  coincident  phenomenon  in  the  neighborhood  of  severe 
inflammatory  processes.  In  the  latter  case  it  is  frequently  designated 
I  collateral  ailema.  Inflammatory  oedema  is  distinguished  from  stagnat  ion- 
jtedema  by  the  fact  that  the  transuded  fluid  is  markedly  richer  in  aJbumhi 
laud  hi  the  number  of  white  hlood-corpuscles  present,  and,  further,  in  the 
I  fact  that  larger  masses  of  coagula  (Fig.  31,  h)  occur  in  it  (see  chapter 
jon  Inflammation).  Its  cause  is  to  be  sought  sometimes  in  infectious  and 
toxic,  sometimes  in  thermal  and  traumatic  influences,  at  other  times  in  a 
temporary  ischiemia. 

As  to  hydraemic  or  cachectic  oedema,  it  was  foi-merly  l)elie\-ed  that 
hydrfemia — that  is,  the  diminution  of  the  solid  elements  of  the  blood — as 
well  as  hydnemic  plethora — that  is,  a  retentiim  of  water  in  tiie  blood^ 
could  directly  cause  an  increased  transudation  from  tlu^  blood-vessels. 
It  was  supposed  that  the  vessel-walls  beha\ed  as  dead  animal  mem- 
jbranes,  and  allowed  a  fluid  poor  in  albumin  to  filter  through  moi'c  <'asily 
[than  one  richer  in  albumin.  The  vessel-wall  is  not,  however,  a  lifeless 
[animal  membrane,  but  must  be  regarded  as  a  liviug  organ.  A  hydra'- 
jmia  experimentally  produced  does  not,  according  to  Cohnheim,  give 
|rise  to  an  oedema.  Even  when  a  hydnemic  plethoi-a  is  ])i-oduced  l)y  the 
over-filling  of  the  blood-vessels  with  a  wateicd  blood,  and  there  results 
,au  inci-eased  transudation  from  the  vessels,  event  ually  leading  to  (edema, 
:the  redema  so  pi-oduced  occurs  only  when  flu?  ])r()portiori  of  water  in  the 
'blood  becomes  very  high,  and  does  not  develop  in  the  same  i-egious  where 
'the  so-called  hydnemic  oedema  in  man  appeals.  We  must  tlierefoi-e  as- 
jsume  that  the  cedema  of  cachectic  individuals,  as  Avell  as  that  occurring 
lin  individuals  suffering  from  nephritis  with  impairment  of  renal  func- 


156  DISTURBANCES    OF    THE    CIRCULATION. 

tion,  depends  essentially  iiiiou  an  alteration  of  the  vessel-wall,  v,liicli  is 
caused  either  by  the  hyditeniic  character  of  the  blood  or  by  a  poison  cir- 
culating- in  the  blood.  Probably  other  lesions  of  the  tissue  through 
which  the  elasticity  of  the  latter  is  diminished  are  also  concerned.  Ry- 
dncmia  therefore  favors  the  occurrence  of  wdema,  but  is  not  the  sole  cause 
thereof,  and,  in  particular,  does  not  determine  its  localization. 

Cachectic  oedema  is  in  part  allied  to  stagnation-oedema  and  in  part  te 
inflanimatoiy  oedema,  in  that  at  onetime  the  circulatory  disturbance  is  a 
prominent  feature,  at  another  time  the  vascular  alteration. 

CEdema  ex  vacuo  occurs  chiefly  in  the  cranial  cavity  and  in  the  spinal 
cord,  and  arises  in  all  cases  in  which  a  portion  of  the  brain  or  spinal  cord 
is  lost  and  not  replaced  by  some  other  tissue.     In  atrophy  of  the  brain 
and  spinal  cord  the  subarachnoidal  spaces  in  pai'ticular  become  enhirged, 
occasionally  the  ventricles  also.     The  fluid  has  the  same  albumin  content ; 
as  tlie  normal  cerebrospinal  fluid.     Local  defects  become  filled  eitlier  by 
a  dilatation  of  the  nearest  subarachnoidal  spaces  or  of  the  adjacent  por- ; 
tions  of  the  ventricles,  or  through  a  collection  of  fluid  at  the  site  of  the  i 
defect  itself.  i 


I 


According  to  Cohnlieim  and  Licldhcim,  injections  of  aqueous  sohxtions  of  salt  into 
the  vascular  system  of  dogs  {Virch.  Arch.,  69  Bd.)  show  tliat  hydrasmia  does  not  pro- 
duce a?dema.     If  the  mass  of  the  fluids  of  the  blood  be  increased,  there  results  an  in- 
crease of  almost  all  the  secretions  (saliva,  intestinal  juices,  bile,  urine,  etc.),  and  also  of 
the  flow  of  the  lymph ;   the  latter,  however,  not  universally,  in  particular  not  in  the 
extremities.     In  a  high  degree  of  hydraemic  plethora  the  abdominal  organs  become 
dropsical,  but  never  the  extremities.      Control-experiments  recently  carried  out  byji 
Francoite  confirm  the  observation  that  hydmemic  plethora  artificially  produced  inani-iv 
mals  causes  in  the  first  place  a  dropsy  of  the  abdominal  organs;   but  this  observer  wasiji    1!' 
able  to  produce  also  an  oedema  of  the  skin  and  subcutaneous  tissues.  [      " 

The  view  that  the  so-called  hydra^mic  o?dema  is  merely  the  result  of  an  increase  Inj 
the  absolute  amount  of  water  in  the  blood,  is  championed  especially  by  w;?,  Heckling-; 
hausen  and  by  Piseiiti.  Tlie  distribution  of  the  dropsy  is,  according  to  von  licckiihg-', 
hnusen,  essentially  dependent  upon  bodily  position,  external  pressure,  impeded  circula-; 
tion,  difference  in  the  innervation  of  diflierent  vascular  areas,  and  the  consequent! 
difference  in  the  fulness  of  their  vessels. 

I  can  subscribe  to  these  opinions  only  in  so  far  as  they  apply  to  the  influence  of  i, 
the  above-mentioned  modifying  factors  upon  the  distribution  of  the  oedema,  but  notii 
as  regards  the  main  point.  For  the  other  side  speak  not  only  the  experiraentsi? 
of  Colmheim  and  Lichtheim  above  mentioned,  but  also  the  fact  that  in  nephritic  and]- 
cachectic  individuals  oedema  not  infrequently  appears  at  a  time  when  no  hydrsemicl 
])lctIiora  is  present;  and,  further,  in  cases  of  hydroemic  plethora  no  oedema  may  occur.' 
I  therefore  look  upon  the  increase  in  the  amount  of  water  as  only  one  factor  which  is 
favorable  to  the  occurrence  of  oedema. 

According  to  the  investigations  of  PiclcJmrdt,  pathological  transudates  constant! 
contain  uric  acid:  the  fluid  of  ascites  about  0.0036  per  cent;  the  fluid  of  oedema,  0.007 
per  cent;  and  pleuritic  exudates  about  0.0015  per  cent.  Sugar  is  also  constantly  preS' 
ent,  usually  as  dextrose. 

Eff unions  into  the  large  serous  cavities  of  the  /wf?y  occasionally  present  a  niilkji  appear- 
ance, or  a  certain  degree  of  opalescence.  This  phenomenon  is  most  often  due  to  the 
presence  of  chyle  {hydrops  chylosus),  or  of  fat  {hydrops  adiposus  or  chyliformi.s),  or  ol 
both.  ]\Ioreover,  the  presence  of  different  albuminoid  bodies,  mucoid  substancefj 
{Ilammarstcn),  casein-like  bodies  {Lion),  lecitliin  {Mitchell,  Mattiroli,  Gross),  may  pro-i 
(luce  cloudiness  of  the  transudate.  In  so  far  as  chyle  is  not  the  cause,  the  substancefi 
pidduciiig  the  cloudiness  arise  for  the  greater  part  from  disintegrating  cells.  Accord  i 
ing  to  Hirnert,  a  cloudiness  maybe  i)roduced  by  albumins  belonging  to  the  group  ol; 
f,^l()l)ulins,  from  which  by  means  of  hot  alcohol  considerable  amounts  of  lecithin  may  b<' 
obtained.     The  fat-content  is,  moreover,  very  low. 

According  to  llcidcnhain,  tlie  specific  function  of  the  capillary  walls  plays  a  con 
trolling  part  in  the  formati(jn  of  the  lymph.  Consequently,  tiie  lymph-production  car 
be  influenced  by  various  substances  present  in  the  blood.  The  crystalloid  substance; 
are  quickly  eliminated  from  the  capillaries,  and  cause  a  discharge  of  tissue-fluid  intci 
tlie  lymph,  as  has  already  been  mentioned  in  §  41.  Reidenhain  has,  however,  founc; 
substances  which,  when  injected,  cause  an  Increase  in  the  transudation  of  water  fronj 


CEDEMA.  157 

the  blood  iuto  the  lyiuph.  This  may  be  accomplished,  for  cxamplo,  with  dt'coctioiis  ot 
the  muscles  of  crabs  and  of  fresh-water  mussels,  or  of  the  heads  and  bodies  of  leeches, 
or  tlirough  injections  of  peptone  and  egi;-albiiniin.  By  tiiese  means  (he  amount  of 
lympli  tlowiuiifrom  tiie  thoracic  duct  may  be  increased  live-,  six-,  and  fifteenl'old.  At 
tiie  same  time  the  amount  of  organic  constituents  in  tlie  lymph  is  increased.  Tlie 
active  substances  must  therefore  stimulate  the  specilic  function  of  the  cells  of  Die 
vessel-walls  which  secrete  the  lym]ih.  According  to  these  observations,  it  is  probable 
that  many  of  the  alTections  of  the  skin  described  as  neuropathic,  and  which  are  ciiarac- 
terized  by  hypenemiu  associated  with  cedematous  swelling — as,  for  example,  urticaria, 
erythema  nodosum,  herpes  zoster— are  to  ])e  regarded  as  symjitoms  of  intoxications 
coupled  with  nervous  alfections  and  with  disturl)ance  of  the  secretorj'  activity  of  the 
capillaries.  It  is  also  possible  that  the  secretion  of  the  capillaries  may  be  directly  af- 
fected bj'  nervous  influences. 

Jfii/jniiit,  on  the  other  hand,  on  the  ground  of  experimental  investigation  (infusions 
of  physiological  salt-solutions  in  normal  animals,  irrigation  of  dead  animals  witli  salt- 
solution  after  poisoning  with  arsenic,  chloroform,  chloral  hydrate,  and  ether,  and  after 
the  removal  of  the  kidneys  and  ligation  of  the  ureters),  arrives  at  the  following  con- 
clusions: The  capillary  walls  during  life  oiler  a  resistance  to  the  iiassage  of  fluids; 
after  death  this  resistance  disappears.  An  injury  to  the  cajiillary  wall,  and  a  diminu- 
tion of  its  resistance,  favor  the  occurrence  of  o'dema.  Tiiere  are  ]K)isons  which  are 
able  to  injure  the  capillary  wall  in  such  a  manner  that  it  becomes  abnormally 
permeable. 

Alba  emphasizes  likewise  the  importance  of  the  increased  permeability  in  the  case 
of  the  escape  of  a  large  amount  of  blood-serum.  H^'draimia  and  plethora  may  con- 
stitute the  conditions  favoring  this. 

Literature. 

{(Edema;  Ufusions  into  the  Bodif-Cavifies.) 

Albu:  Ex]ier.  Eizeugung  v.  Oedemen.     Yirch.  Arch.,  166  Bd.,  Berlin,  1901. 
Asher  u.  Barbera:  Eigensch.  u.  Entstehung  d.  Lymphe.     Zeit.  f.  Biol.,  1897. 
Bargebuhr:  C'hy lose  Erglisse  in  der  Pleura.     Dent.  Arch.  f.  klin.  Med.,   r)3  Bd.,  1895 

(Lit.). 
Bernert:  :\rilchige,  nicht  fetthaltige  Ergilsse.      Arch.  f.  exp.  Path.,  49  Bd.,  1903. 
Bernlieim:  Beiu.  z.  Chcmie  der  Exsudate  u.   Transsudate.     Yirch.   Arch.,   131   Bd., 

Boddaert:  Develojip.  de  Tredeme.     Ann.  de  la  Soc.  med.  de    Gand,    1893;    (Edc^me 

1        lynipliatiiiue.     Acad.  Koy.  de  med.  de  Belgique,   1895;  Influence  de  riiinervalion 

I        Kur  la  transsudation  vasculaire.  1903. 

iCitron:   Eiweissgehalt  u.  spec.  Gewicht  pathol.  Flussigkeiten.     Deut.  Arch.  f.  kl. 

i        Med..  46  Bd.,  1890. 

ICohnheini:   AUgem.  Pathologic,   1882;   Untersuch.  lib.   d.  embolischen  Processe,  Bcr- 

'        lin.  lsT-2. 

Cohnheim  u.  liicMheim :    Ueber  Hydrilmie  u.  h^draiuisclies  (Edem.     \neli.  Arch., 

09  Bd..  1877. 
iCohnstein:    Transsudation   u.    Lymphbihlung.      Yirch.    Arch..    i;!5   Bd.  :    Pfliiger's 
Arch.,  59  Bd.,  1894;  (Edem  u.  Hydrop.s.     Ergebu.   d.  allg.  Path.,  ni.,  ^\  lesbadeu, 
I        1897  (Lit.).  ,   ,      1      , 

'Emminghaus :  Abhangigkeit  d.  Lymphabsonderungen  v.  Blutstrom.     Arb.  d.  phys. 
Aii'-t.  zu  Leipziir.  viii.,  1874.  - ,    -r.  ,    • 

Francotte:    De  I'a^deme  hydremique.     Bull,  de  I'Acad.  Boy.  de  med.  Belgique,  ii., 
Bruxelles.   1S88. 

Gross:  Pseudnrjiylose  Erglisse.     Arch.  f.  exp.  Path.,  44  Bd.,  1900. 

Grossmann:  .Muscarinlungenodem.     Zeitschr.  f.  klin.  Med.,  xii.,  1887. 

Halliburton:  Chcmische  Phvsioloirie  u.  Patliologie,  Heidelberg.  1893. 

Hamburger:  Ilvdrops  von  n'likrobii'liem  I  isprung.     lieitr.  v.  Ziegler,  xiv.,  1893. 

Hammarsten :   ■Mucoidsubstanzen  in  Ascitestliissigkeit.     Zeit.   f.   phys.   t'hem.,   xv., 

i       1!^91. 

iHeidenhain:    Zur  Lehre  von  der  Lvmphbildung.     Yerhandl.  d.   X.    mternat.   med 

!        Con-r..  ii.,  P,erlin,  1891;  Arch.  f.\l.  ges.  Phys..  49  Bd.,  1S91. 

rousset:  Des  humeurs  opalescentes  de  I'organisme,  Paris,  1901. 

^lebs,  A.:  (Edem  d.  Ilornhautepithels.     Beitr.  v.  Ziegler,  xvii.,  1895. 

wanderer:  Die  Gewebsspannung,  Leipzig,  1884.  m   ni 

il^assar:  Ueber  (Edem  u.  Lymphstrom  bei  der  Entzlindung.     ^  irch.    Arch.,  hJ   Bd., 

1       1H77. 

iiazarus:  The  Pathol,  of  (Edema.     Brit.  Med.  Journ.,  i.,  1895. 


I 


15S  DISTURBANCES    OF   THE    CIRCULATION. 

Leydhecker:   Carciuom  d.  Duct,  thoracicus  mit  chylosem  Ascites.     Virch.  Arch.,  134 

15(1. ,  1893. 
Lion:  Ascite  laiteuse  nou  chj^leuse.     Arch.  d.  med.  exp.,  xv.,  1893. 
Lowit:    p]ntstcliiin!?  d.   Lungenodems.     Beitr.   v.  Ziegler,   xiv.,  1893;    Lungenodem, 

(Viit.  f.  a.  Path":,  1895. 
Lukjanow:  Allgem.  Pathologic  des  Gefassystems,  Leipzig,  1894. 
Mag-nus:  Entstehung  d.  Hautodeme  bei  hydr.  Plethora.     Arch.  f.  cxp.  Path.,  42  Bd., 

IS!)!). 
Munk;  Transsudate.     Eulenburg's  Realencyklop.,  xxiv.,  1900. 
Pickardt:  Zur  Chemie  patholog.  Ergiisse.     Berl.  klin.  Woch.,  1897. 
Pisenti:  Beitrag  zur  Lelire  von  den  Transsudaten.     Cbl.  f.  allg.  Path.,  ii.,  1891. 
Quincke :    Hydrops  chylosus  u.  adiposus.     Deut.  Arch.  f.  klin.  Med.,  6Bd. ;  Ascites. 

11).,  ;!or,(i. 

Quincke  ii.  Gross:  Lokalisat.  d.  akuten  umschrieb.  CEdems.     D.  med.  Woch.,  1904. 

V.  Recklinghausen:  Handb.  d.  allg.  Path.  d.  Kreislaufs  u.  der  Ernilhrung,  Stutt- 
gart, 18S3. 

Reuss:  Vcrhilltn.  d.  spec.  Gew.  z.  Eiweissgehalt  in  serosen  Flussigkeiten.  Deut. 
Arch.  f.  klin.  Med.,  38  Bd.;  Beurtheilung  von  Exsudaten  und  Transsudaten. 
lb.,  24  Bd. 

Senator :  Ueber  Transsudation  und  ilber  den  Einfluss  des  Blutdrucks,  auf  die  Beschaf- 
fenheit  der  Transsudate.  Virch.  Arch.,  Ill  Bd.,  1888;  Ascites  chylosus  u.  Chylo- 
tliorax  bei  Carcinom  d.  Ductus  thor.     Cbl.  f.  inn.  Med.,  1896. 

Starling-:  On  Absorption  from  and  Secretion  into  the  Serous  Cavities.  Journ.  of 
Phys. ,  xvi.,  1894 ;  The  Influence  of  Mechanical  Factors  on  Lymph  Production.  lb., 
1894;  Action  of  Lymphagogues.  lb.,  xvi.,  1894;  Absorption  of  Fluids  by  Blood- 
vessels,    lb.,  1896;  The  Causation  of  Dropsy.    Lancet,   1896. 

TcMrkoff:  ffidemes  vasomoteurs.    Rev.  de  med.,  xv.,  1895. 

Ziegler,  K.:  Oedem    der    Haut    und    des    Unterhautzellgewebes.     B.    v.    Ziegler, 
XXX  vi.,  1904. 
See  also  §  46. 

V.  Haemorrhage  and  the  Formation  of  Infarcts. 

§  43.  By  haemorrhage  is  understood  the  escape  of  all  the  constituents 
of  the  blood  from  the  vessels  (extravasation)  into  the  tissues  or  upon  a 
free  surface.  It  may  be  either  arterial,  venous,  or  capiUari/,  or  the  blood 
may  escape  from  the  heart.  The  blood  which  has  escaped  from  the  vas- 
cular system  is  termed  an  extra vasate.  For  the  designation  of  especial 
forms  of  haemorrhage  a  ^ery  great  variety  of  terms  is  used.  If  the 
hsemorrhagic  foci  are  small,  and  form  more  or  less  sharply  outlined, 
punctate,  red  or  dark-red  spots,  they  are  caWed  2)etecMw  or  ecehjimoses;  '  ^ 
if  they  are  larger  and  not  sharply  outlined,  they  are  known  as  suygiUa-  J^" 
tions  and  as  hloody  suffusions.  If  the  affected  tissue  is  firmly  infiltrated  ''"I 
with  the  escaped  blood,  but  not  torn  or  destroyed,  the  condition  is  spoken  \ 
of  as  a  lunnorrluujic  infarct.  If  the  extravasated  blood  forms  a  large  j  ^^ 
mass,  this  is  known  as  a  luematoma  or  Mood-tumor.  \     *' 

The  l)lo()d  which  escapes  from  the  vessels  into  the  tissues  collects  at;  *'' 
first  in  tlie  tissue  S])aces  (Fig.  32).  Large  hsemorhages  may  completely  j^'^Ji 
conceal  the  stru(^ture  of  the  tissue  (Fig.  33,  d).  Delicate  tissues,  as  those | 
of  the  brain  or  spinal  cord,  may  be  destroyed  by  large  haemorrhages.       j 

If  the  luemoi-rhage  occurs  on  the  free  surface  of  an  organ,  the  bloodi 
either  escapes  externally  or  is  i^oured  into  a  neighboring  cavity. 

Ilfcmorrhage  from  the  nose  is  called  epistaxis ;  vomiting  of  blood,] 
Jueniatriiie.sis  ;  bleeding  from  the  lungs,  hwmoptoe  or  limmoptysis;  from  thel' 
uterus,  nutforrhafjia  and  menorrhac/ia  (during  the  menses)  ;  hsemorrhageij; 
from  llie  urinary  organs,  luvmaturio;  hemorrhage  from  the  sweat-glands,!; 
hwuKiiidrosis. 

A  collection  of  lilood  in  tlie  uterine  cavity  is  designated  as  hamato-' 
metra,  in  the  pleural  cavity  as  hmmothorax,  in  the  tunics  of  the  testicle  as 
h(ematocclr,  in  the  pericardium  as  hwmopericardium. 


ii 


\ 


HAEMORRHAGE. 


150 


IlaMiiorrliaoos  of  the  skin  not  canscd  l)y  tiaiima  aic  nsiiall\ 
purpura  (Fiir.  '^2^.  Collections  of  blood  ami  lluiil  beiu-atli  the  cp 
in  tlic  i)]ac'e  of  the  dissolved  deeper  epithelial  layers  ^ive  rise  to 
rhafjic  hh-hs. 


IcniH'd 
(U'liiiis 
lidiuor- 


FlG.  32.— Haemorrhage  in  the  skin  near  the  knee;    from  a  man  eighty-one  years  of  age.     (Formalin, 
hematoxylin,  and  eosin.)     X  80. 


Eeeent  extravasations  show  the  characteristic  color  of  either  arterial 
or  venous  blood.  Later  the  extravasate  shows  various  alterations  wliich 
are  characterized  particularly  by  color-changes.  Suggillations  of  the 
skin  become  first  brown,  then  blue,  and  green,  and  finally  yellow.  In 
the  course  of  time  the  extravasate  is  absorbed  (see  Chapter  V.),  and  dur- 
ing this  absorption  tissue-proliferation  often  occurs.  Large  collections 
of  blood  may  become  partly  organized  into  connective  tissue  or  may 
become  encapsulated  (see  Chapter  YII. ). 

A  hsemorrhage  may  occur,  in  the  first  place,  from  rupture  of  the 
|heart  or  the  vessel=wall — that  is,  per  rhexin  or  per  diabrosin.  This  is 
|the  only  form  of  cardiac  and  arterial  hcX»niorrhage.  From  the  capillaries 
and  veins  luemorrhage  may  occur  also  per  diapedesin — that  is,  by  a  proc- 
ess in  which  the  red  cells  escape  through  the  vessel-wall  without  the  oc- 
currence of  a  tear  in  the  same.  Very  often  such  ha;morrliages  are  small 
and  of  slight  extent;  in  other  cases  the  process  continues  for  a  longer 
time,  and  the  infiltration  of  the  tissues  with  red  cells  reaches  a  significant 
degree.  Hiemorrhages  by  diapedesis  are  thei-efore  not  always  small, 
ihsemorrhages  by  rhexis  not  always  large.  The  iii])tnre  of  a  capillaiy 
pr  small  vein  does  not  gi\e  rise  to  a  large  ha'morihagc;  on  the  other 
naud,  ahiemorrhagc  tlii-ougli  diapedesis  can  reach  an  iinpoitant  size. 
1  The  causes  of  interruption  of  continuity  of  the  heart-wall  and 
vessel-walls  are  in  i)art  trauniatir  injuries,  in  pail  iwrra.sr  of  intra  nis- 
\ular pressure,  and  in  pai't  dificasrd  cdikHHou-s  of  t/ir  hiarl  dud  rrssrl-indf. 
jlncrease  of  the  blood-pressure  in  the  capillai'ies  and  smalhv^t  veins  can 
lead  to  rupture  without  the  aid  of  vascular  changes,  ])arliculai]y  in  the 
j-avseof  marked  passive  congestion.  The  heart,  normal  arteries,  and  noi-- 
jnal  veins  of  large  size  cannot  be  ruptured  through  inci-easr  of  ])ressiire 
'ilone,  but  abnormally  thin- walled  or  diseased  areas  in  eithci-  the  heart, 


160 


DISTURBANCES    OF   THE    CIRCULATION. 


arteries,  or  veins  may  be  so  ruptured.     Xewly  formed  vessels  are  easily 
torn. 

Diapedesis  may  be  caused  by  au  increase  of  pressure  iu  the  capillaries 
and  veins,  as  well  as  by  an  increased  permeahility  of  the  vesseJ-ivall. 
K  the  out  How  of    the  venous  blood  in  a  given  vascular  area  be  ob- 


i:: .'.  -yfi.  ::^r-^s^^&;^:^^ 


_  Fig.  33. — Traumatic  cerebral  hemorrhage.  (Formalin,  hscmatoxylin,  and  eosin.)  a.  Normal 
brain  substance;  b,  blood-vessel;  c,  perivascular  collection  of  blood;  d,  larger  area  of  hemorrhage 
with  destruction  of  the  brain  substance,     x  100. 


structed,  diai)edesis  of  red  cells  from  the  capillaries  and  veins  takes  place; 
and  this  is  to  be  regarded  as  a  result  of  the  increased  pressure  iu  the  ves- 
sels. Diapedesis  as  a  result  of  changes  in  the  vessel-wall  occurs  particu- 
larly after  mechanical,  chemical,  and  thermal  lesions  of  the  vessel ;  and 
it  may  be  assumed  that  certain  jyoisons  produce  especially  marked  changes 
iu  the  vessel-walls.  Further,  an  abnormal  permeability  of  the  vessel- 
walls  is  also  observed  when  for  a  long  period  the  vessels  have  not  been 
traversed  by  the  blood-stream,  and  have  suffered  in  their  nutrition  lu 
consequence. 

"When  an  individual  shows  a  special  tendency  to  h?emorrhage,  the 
condition  is  designated  as  haemorrhagic  diathesis.  Two  forms  may  be 
distinguished — a  congenital  and  au  ac(piired. 

Tile  congenital  haemorrhagic  diathesis  or  congenital  haemophilia, 
which,  as  already  mentioned  in  §§  15  and  IG,  belongs  to  the  diseases 
which  may  be  inherited,  depends  most  probably  upon  an  abnormal  con- 
stitution of  the  vessel- walls.  The  composition  of  the  blood  may  also  be 
pathological,  so  that  a  hemorrhage  once  started  is  not  arrested,  as  usual, 
by  the  coagulation  of  the  blood. 

An  acquired  hemorrhagic  diathesis  occurs,  in  the  first  place,  in| 
those  diseases  which  are  known  as  scurvy,  morbus  maculosus  Werlhofii, 
purpui  a  simplex,  puri)ura  (peliosis)  rheumatica,  purpura  hieinorrhagica, 
haimophilia,  and  melana  neonatorum  (gastric  and  intestinal  haemor- 
rhages), and  Holler's  or  Barlow's  disease;  and,  further,  iu  many  iufec- 


i: 


HEMORRHAGE.  Ifil 

tions  ami  intoxications — namely,  se])tic{e.mia,  endocarditis,  anthrax, 
tyi)hns  lever,  cholera,  smallpox,  plai;ue,  acnte  yellow  atrophy  of  the 
liver,  yellow  fever,  nephritis,  phosphorns  poisoning;',  aftei-  snakebites, 
etc.  ;  and,  finally,  also  in  i)ernicions  ana'uiia.,  lenkiemia,  and  i)seud()U'n- 
ka'iuia.  In  the  first  gi'oup  of  diseases  named — all  of  which  are  charac- 
terized by  ha'morrha.u'es  in  the  skin,  mucous  membranes,  and  i)arenchyma 
of  varit)us  organs  and  tissues  (in  IJarlow's  disease,  which  often  occuis  in 
children  of  from  one  and  one-lialf  to  two  years  old  in  association  with 
rickets,  the  ha'morrhagcs  are  subperiosteal) — the  cause  has  been  «»ener- 
ally  supposed  to  lie  in  ilisfurbonccs  of  nuirition  and  of  the  circuJaUon ;  but 
recent  observations  make  it  very  probable  that  these  affections,  at  least 
in  a  great  iiart,  belong  to  the  infections  diseases.  W.  Koch  is  of  the  opin- 
ion that  scurvy  is  an  infections  disease,  and  that  the  different  forms  of 
purpura,  erythema  nodosum,  and  the  hjemorrhages  occurring  in  the  new- 
boiu  represent  varieties  of  this  infection.  In  the  last  few  yeais  bacteria 
have  been  repeatedly  found  in  these  conditions — namely,  ])nipura  luenior- 
rhagica  and  the  hiemophilia  of  the  new-born.  In  this  coiuiection  should 
be  mentioned  especially  the  investigations  of  Kolb,  Babes,  (itirtner,  Car- 
riere,  Tizzoui,  and  Giovannini,  who  have  found  in  these  diseases  certain 
bacilli  which  were  pathogenic  for  animals,  and  which,  when  inoculated 
into  the  latter,  produced  a  disease  characterized  by  haemorrhages.  These 
diseases  are  also  associated  with  other  infections  characterized  by  luem- 
orrhages,  and  it  may  be  assumed  that  the  haemorrhages  are  in  ])ait^  caused 
by  local  changes  of  the  I'essel-ivall  which  are  due  to  local  dcrrJopineiti  (f  bac- 
teria, and  in  part  to  the  injurious  influence  of  the  toxic  substances  produced  by 
the  bacteria  themselves. 

The  haemorrhages  occurring  in  anaemic  conditions  are  to  be  regarded 
as  the  result  of  anceniic  degeneration  of  the  vessel-ioall,  though  partly  also 
as  a  result  of  circulatory  distm^bances. 

A  number  of  apx)arently  spontaneous  haemorrhages  are  connected  with 
irntation  or  paralysis  of  the  vasomotor  nerves,  arisiug  either  from  the  cen- 
tral nervous  system  or  by  reflex  action,  or  through  lesions  of  the  con- 
jducting  nerve-fibres.  In  this  category  belong  the  hiemorrhage  of  men- 
[struatiou,  many  forms  of  haemorrhage  from  the  nose,  intestine,  and 
jurinary  bladder,  also  haemorrhages  from  the  conjunctiva,  skin  (stigmati- 
jzation),  from  the  normal  kidney,  mammary  glands,  from  hsemorrhoids, 
wounds,  etc.  Further,  certain  haemorrhages  from  the  lungs  following 
severe  cerebral  lesions  are  also  to  be  considered  in  this  connection, 
though  in  a  given  case  it  is  not  always  possible  to  judge  with  certainty, 
junce  disturbances  of  respiration,  as  well  as  the  aspiration  of  irritating 
ludjstances  into  the  lungs,  may  likewise  lead  to  hyperaemia  and  to  luemor- 
•liages  in  the  lung.  Finally,  in  cerebral  disease,  pait icnlaily  in  disease 
i)f  the  crura  cerebri,  there  occur  haemorrhages  fi'om  the  stomach  and  iu- 
[estines,  which  are  dependent  upon  the  cerel)ial  lesion. 

1  Hemorrhages  per  rhexin  cease  when  the  extra  vascular  pressure  comes 
0  equal  the  pressure  within  the  bleeding  vessel,  or  Miien  tin;  narrowing 
f  the  vessel  and  the  processes  of  coagulation  and  thrombosis  close  the 
[ent.  Hcemorrhage  by  diapedesis  ceases  through  a  cessation  of  blood-sup- 
»ly  to  the  bleeding  vessel,  or  when  the  abnormal  intravascular  i)ressure 
p  lowered  and  the  vessel-wall  is  restored  to  its  normal  state. 

I  The  process  of  diapedesis  may  be  observed  under  the  microscope  in  tlie  froi^^'s 
liesentery  or  web.  If  before  the  examination  tlic  efferent  veins  are  ligated,  tlie  capil- 
iries  and  veins  are  seen  to  be  engorged  with  blood.     After  a  certain  time  the  red 

n 


162  DISTURBANCES    OF   THE    CIRCULATION. 

blood  cells  begin  to  pass  from  the  capillaries  and  veins  (see  Cohnheim  "  Allgem.  Path.," 
I.,  and  Virch^Arch:,  41  Bd.).  Arnohl(Vnrh.  Arch. ,58,  62  ii  64  B.l.)  behevod  at  first 
that  at  the  place  of  exit  of  the  corpuscular  elements  spaces  bet^vee^  the  endothe  lal 
cells  must  exist,  and  these  he  designated  as  stigmata  and  stomata;  later  he  found  that 
the  supposed  openings  consisted  of  more  marked  heaping-up  of  the  cement-substance 
between  the  endothelial  cells.  Under  pathological  conditions  the  cement-substance 
gives  way  and  allows  the  red  blood-cells  to  pass  through. 


It 
6 


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Jelin:  lilutaustrittc  in  d.  Lungengevvebe  bci  Hirnleiden.     (;i)l.  f.  d.  nied.  Wiss.,   1874 
Klemperer:  Nicroublutimgeu  b.  gcsundeu  Nieren.     Dcut.  uicd.  Woch.,  1877. 
Nothnagel:  Ilirnveilct/ungen  u.  Limgcuhilmorrliagie.     Cb.  f.  d.  incd.  Wiss.,  1874. 
Ollivier:    Do  I'aix^pk'xio  pidmonairc  uuilatt-ralc  dans  scs  rapports  avec  rheniorrliagie 

crrrhialc.     Arch.  gc'n.  de  nu'd.,  1878. 
Pisenti:  Eniorragic  da  causa  nervosa.     Lav.  dcU'  Instit.  Anat.  Patol.  di  Perugia,  1890. 
V.  Preuschen:   Verletzungen  dos  Kiudes  als  Ursache  der  Melaena  noouatoruin,  Wicn, 

ISIM. 
V.  Recklinghausen:  Allg.  Pathol,  des  Ivreislanfs  u.  der  Ernilin-ung,  Stuttgart,  1883. 
Vulpian:  Le(;ons  sur  I'appareil  vasomoteur,  1875. 

§  44,  The  sudden  closure  of  an  artery  by  tlirombosis,  or  eiubolisiu, 
or  by  ligation,  or  by  any  other  means,  leads,  as  has  already  been  stated 
f§  39),  to  a  stoppage  of  tlie  circulation  bej^ond  the  point  of  obstruction, 
after  the  vessel  has  more  or  less  completely  emptied  itself  by  the  con- 
traction of  its  walls.  At  the  same  time  there  is  an  increase  of  i)ressure 
in  the  vessel  from  the  point  of  obstructiou  back  to  the  point  of  divergence 
of  the  uearest  arterial  brauch.  If  the  branches  of  the  artery  beyond  the 
l)oint  of  obstructiou  have  free  arterial  communicatiou  with  some  other 
|nnobstructed  artery,  the  latter  by  becoming  dilated  may  be  able  to  sup- 
jply  a  sufficient  amount  of  blood  to  the  affected  area  and  the  circulation 
|is  thus  restored. 

i  If  the  area  of  the  obstructed  artery  has  no  collateral  connections 
through  which  it  may  draw  its  blood-supply,  the  portion  of  tissue  de- 
prived of  blood  remains  antemic  and  dies,  thus  giving  rise  to  an  anaemic 
infarct.  Parenchymatous  organs^as,  for  example,  the  spleen  and  the 
-cidneys — present  in  such  infarcted  areas  a  cloudy,  opaque,  yellowish- 
:.vhite,  often  clay-colored  appearance.   (See  §48.) 

i  When  the  area  of  distribution  of  the  obstructed  xessel  possesses  no 
[collateral  anastomoses,  as  in  the  case  of  a  terminal  artery,  but  if,  on  the 
|)ther  hand,  there  is  a  scanty  influx  of  blood  from  neighboring  ca]>illaries 
j^r  from  the  veins,  a  haemorrhagic  infarct  may  be  formed.  The  capil- 
laries of  the  area  rendered  aiuemic  by  tlie  obstruction  become  gradually 
|illed  once  more  v>-ith  blood,  which  in  part  comes  from  tlui  capillaries  of 
|he  adjacent  vascular  area,  and  in  part  from  the  veins,  from  which  the 
Mood  floMs  in  a  retrograde  direction.  The  blood  flowing  in  from  the 
djacent  capillaries  is  under  very  low  pressure,  which  is  not  sufficient  to 
irive  the  blood  C|uiclvly  through  the  obstructed  area  into  the  veins. 
V'hen  the  conditions  of  pressure  become  such  that  a  retrograde  current 
ets  in  from  the  veins  into  the  ca])illaries,  tlie  restoi*ation  of  the  normal 
Sirculatiou  becomes  wholly  impossible. 

The  impeifect  circulation  in  the  obstructed  area,  which,  through  proc- 

isses  of  coagulation  in  llie  veins  and  ca])illaries,  is  linally  lu-onglit  to  ;b 
omplete  standstill,  leads,  in  case  there  is  not  a  restoration  of  the  noi-iual 
ow  of  blood  in  the  vascular  system  through  a  speedy  adjustment  of  press- 
re,  sooner  or  later  to  a  degeneration  and  necrosis  of  tlie  ves.sel-wall, 
jUd  thereby  to  an  increased  permeability  of  the  same.  As  a  i-esult,  if 
;tie  afflux  of  blood  be  continued,  there  occur  in  the  stagnated  area  a  dia- 
'cclesis  of  red  cells  and  an  infiltration  of  the  tissue  with  extravasated  hlood- 
jorpuscles,  through  which  the  ol)structed  area  acquires  a  daik-red  color 
lid  a  firmer  consistency;  a  luemovrhagic  infarct  is  thus  formed  (Fig.  .'{4). 


164  DISTURBANCES    OF    THE    CIRCULATIOX. 


Emholie  hcemorrhagic  infarcts  occur  iu  the  luugs  (Fig.  34),  but  a 
formed  after  the  embolic  obstruction  of  an  artery  only  when  there  eXi 
a  2)((stiicc'  conf/cstion  of  the  Jungs ;  Avhile  in  the  case  of  a  normal  pulmonary 
circulation  the  disturbances  of  circulation  produced  by  the  embolism  are 
quickly  compensated.  In  the  systemic  circulation  extensive  embolic 
haemorrhages  are  confined  almost  entirely  to  the  region  of  distribution 


ar&l 
ist^ 


Fig.  ;U.-Ha-mmTlia<ric  infarrt  of  tlif-  luntr.  i  H;ematox\iin  ami  t-nsin.')  Alvmii  filled  with  bloc 
scattered  pale  nuclei  in  the  alveolar  septa  and  in  the  blood  of  the  alveolar  spaces,  belonging  partly  to  co 
nective-tissue  cells  and  partly  to  leucocytes.    X  40. 

of  the  superior  mesenteric  artery,  whose  branches,  though  not  termini' 
arteries,  possess  but  few  anastomoses.     Ancemic  infarcts  occur  especial!- 
in  the  spleen,  heart,  and  'kidneys.     Around  the  periphery  of  the  anam 
area  there  is  always  more  or  less  hemorrhage,  so  that  the  pale  area  < 
the  infarct  is  surrounded  by  a  hcemorrhagic  border  or  at  least  by  hcemo. 
rhayic  spots.     Iu  the  case  of  obstruction  of  the  cerebral  arteries  or  thoi 
of  the  extremities,  or  the  central  artery  of  the  retina  punctate  Iutpiuo- 
rhages  may  also  occiu\     Within  the  infarcted  area  the  tissues  are  whol 
or  for  the  greater  part  dead,  and  the  specific  elements  of  the  organ  ' 
particular  (Fig.  36,  c,  d)  die  quickly.     After  a  time  an  exudative  inflai! 
matiou  arises  in  the  neighborhood  of  anaemic  and  hfemorrhagic  infarct* 
with  the  formation  of  a  cellular  (Fig.  36,/)  or  a  cellular  and  fil)rino 
exudate;  and  this  is  foUoAved  by  tissue-i^roliferation  through  which  t 
dead,  luemorrhagic  area  is  gradually  absorbed  and  replaced  bv  count 
tive  tissue  (see  Part  II.  of  Chapter  VII.). 

Tirchiir,  wlio  was  tlie  first  to  carry  out  extensive  experimental  investigatic  • 
with  reference  to  tlironibosis  and  embolism,  leaves  iu  his  published  works  the  quest 
of  tlie  origin  of  embolic  h.-emorrhagic  infarcts  still  open;  but  expresses  the  opinion  t); 
most  probably  the  vessel-walls  in  the  obstructed  area  suffer  changes  bv  which  tl 
])ecome  more  permeable  and  fragile.  If  a  collateral  circulation  be  afterward  est;- 
lished,  secondary  luemorrhage,  exudation,  and  extravasation  take  place  as  the  result: 
the  clianges  in  the  vessel-wall.  Cohnheim,  who  studied  the  results  of  embolism  in  i 
frog's  tongue  directly  under  the  microscope,  demonstrated  the  retrograde  flow  of  bid 
in  the  veins,  the  retilHng  of  the  capillaries,  and  the  escape  of  blood  by  diapede'. 
Tlie  cause  of  the  diapedesis  he  believed  to  be  essentially  the  disorganization  of  3 


ANEMIC    IXFAHCTIOX.  165 

vessel-wall  caused  by  the  anemia.  Liiten  regarded  the  retrograde  flow  of  blood  from 
the  veins  as  iinessential,  ami  referred  I  lie  reiiliiiig  of  the  ana'iuio  area  to  an  influx  of 
blood  from  the  capillaries  of  the  neighboring  vascular  areas.  He  also  regarded  the 
disorganization  of  the  vessel-walls  as  unnecessary  for  the  ])roduction  of  infarction,  in- 
asmuch as  the  stagnation  is  sufficient  in  itself,  as  "in  the  case  of  venous  obstruction,  to 
explain  the  diapeiiesis.  The  diaiiedesis  is  therefore  increased  whenever  in  such  foci 
the  blood  coagulates  in  the  elfei-eut  veins.  Von  lieckliiu/haitsen  considers  the  prin- 
cipal factor  in  the  formation  of  a  htemorrhagic  infarct  to  be  a  hyaline  thrombosis  of 
the  capillaries  of  the  obstructed  area.  If  blood  subsetjuently  enters  from  neighljoriug 
vessels  into  the  still  pervious  vessels  of  the  area,  it  encounters  resistance,  becomes 
stagnant,  and  then  escapes  from  the  vessels. 

"The  essential  cause  of  the  escape  of  blood  in  the  case  of  ha3morrhagic  infarction  lies 
in  the  stagnation  of  the  blood  in  the  affected  area,  and  in  the  degeneration  or  death  of 
the  tissue  and  the  blood-vessel  walls.  The  latter  change  may  be  recognized  with  cer- 
tainty through  the  disappearance  of  the  nuclei.  Secondary  thrombosis  in  the  vessels  of 
the  obstructed  area  is  of  frequent  occurrence,  and  increases  tin;  stagnation  and  lia'inor- 
rhage,  but  thrombi  are  not  always  present  at  the  time  of  ti'c  h;emorrhage,  and,  therefore, 
cannot  be  regarded  as  the  essential  factorin  the  production  of  the  latter. 

According  to  investigations  by  Orth.  ha-morrhagic  infarcts  may  be  produced  in 
dogs  through  the  introduction  of  chemically  irritating  emboli  into  the  pulmonary 
arteries. 

In  the  lungs,  in  conditions  of  passive  congestion  and  inflammation,  there  not  infre- 
quently occur  extensive  hjen^.orrhages,  which,  in  case  they  are  restricted  to  a  circum- 
scribed" area,  closely  resemble  embolic  infarcts.  They  are  usually  less  sharply  outlined 
and  less  firm,  so  that  in  the  majority  of  cases  they  are  easily  d'istiuguished"  from  the 
embolic  infarcts. 

Literature. 

(Hwmorrhaf/ic  Infarction. ) 

Cohn:  Klinik  der  embolischen  Gefiisskrankheiten,  Berlin,  1860. 

Cohnheini:   Untersuch.  lib.  d.  embol.  Processe,  Berlin,  1872;  Allgem.  Pathol.,  Berlin, 

1S82. 
Faber:  Die  Embolic  der  Art.  mesenterica  sup.     Deut.  Arch.  f.  klin.  ]\Ied.,  187o, 
Fischer:  Ueber  die  Embolic  der  Art.  centralis  retinae,  Leipzig,  1890. 
Grawitz:   Die  hamorrhag.  Infarkte  d.  Lungen.     Festschr.  d.  Assist,  f.  Virchow,  Ber- 
lin. 1891. 
Kaufmann:   Verschluss  d.  Art.  mesenterica  sup.  durch  Embolic.     Yirch.  Arcii.,  116 

Rd.,  1889. 
Krebs:   Hyaline  Thromben  in  hamorrhagischen  Infarkten      Beitr.  v.  Ziegler,  ii.,  1888, 

p.  472. 
Litten:   Ueber  die  Folgen  des  Verschlusses  d.  A.  mesent.  superior.     Virch.  Arch.,  63 

Bd.,  1875;  Untersuchungen  iiber  den  hiimorrhagischeu  Infarkt,  Berlin,  1879. 
Lukjanov?:  Allgem.  Pathologic  dcs  Gcfiissy stems,  Leipzig,  1895. 

Mogling:  Zur  Kenntniss  dcs'hamorrhag.  liifarktes.     Beitr.  v.  Ziegler,  i.,  Jena,  1886. 
Dbermuller:  llvaiine  Thrombusbilduug  u.  hamorrhag.  Lungeninfarkte.     Inaug.-Diss., 

Strasshuri,^,  ISSG. 
Drth:  Hr/cuguiig  des  hamorrhag.  Infarktes.     Cbl.  f.  allg.  Path.,  1897,  p.  859. 
7.  Recklinghausen:   Handb.  d.  allg.  Path.  d.  Kreislaufs  u.  d.  Erniihrung,  Stuttgart, 

iss;!. 
iibbert:  Niereninfarkte.     Vircli.  Arch.,  155  Bd.,  1899. 

ichaflfer:  Ueber  das  sog.  H^valin  in  Lungeninfarkten.     Fortsch.  d.  .Med.,  vi.,  1888. 
/irchowr:  Handb.  d.  spec.  Pathol.,  i.,  1854:  Ges.  Abhaiidl.,  Fraiddurt,  1850. 
Velch:  Ibemorrhagic  Infarction.     Trans.  Assn.  Amer.  Phys.,  18S7. 
Villgerodt:    Hilmorrhag.  Infarkte  d.  Lunge.     Arb.  a.  d.  path.   Inst,   zu  Gottingen, 
:       B.Tlin,  1893. 

[Voolley:  Thrombosis  of  the  Central  "Vein  of  the  Right  Adrenal  with  Engorgement 
I      and  Necrosis  (Infarction).     Jour,  of  3Ied.  Besearch,  1902. 

VI.  Lymphorrhagia. 

§  45.  Lympherrhagia  occtii-s  -vvIumi  the  coiitiimity  of  :i  lyiiii)li-\esst*l 
5  interrupted  at  any  point  and  the  ]ymi)h  is  poured  out  into  the  neif^li- 
oring  tissue.  Since  the  pressnre  in  ilie  lympli-vessels  is  v<mt  low— tliat 
>,  not  greater  than  in  the  surrounding   tissues — an  otillluw  «>f  lymph 


166  DISTURBANCES    OF   THE    CIRCULATION. 


1 


from  a  lymph -vessel  can  occur  only  when  the  injured  vessel  lies  on  the 
external  surface,  or  Avheu  a  natural  cavity  is  at  hand  into  which  the 
lymph  can  how,  or  when,  through  the  same  cause  producing  the  rupture, 
an  open  space  is  formed  at  the  same  time  in  the  tissues.  So,  for  exam- 
ple, an  escape  of  lymph  together  with  the  blood  may  take  place  from 
wounds,  but  the  outflow  is  stopped  by  very  slight  counterpressure.  If, 
after  the  wounding  of  a  lymphatic,  the  opening  persists,  so  that  there  is 
a  pei-manent  outflow  of  lymph,  escaping  externally  (as  in  ulcers)  or  intc 
one  of  the  body-cavities,  there  is  formed  a  Iymph=fistula,  through  which, 
considerable  cpiantities  of  lymph  may  be  lost.  Most  important  and  also, 
most  dangerous  is  the  rupture  of  the  thoracic  duct,  which  occurs  sometimes 
as  the  result  of  traumatism,  and  occasionally  as  a  result  of  an  obstruc 
tiou  to  the  lymph-flow  at  some  point  in  the  lumen  of  the  duct  (after  in  i 
flammatiou  or  in  the  course  of  the  growth  of  tumors).  The  lymph  if 
poured  out  into  the  thoracic  or  abdominal  cavity,  giving  rise  to  a  chylou, 
hydrothorax  or  a  chylous  ascites,  or  in  very  rare  cases  to  a  chyloperieardium. 

In  very  rare  cases  it  happens  that  the  urine,  as  it  conies  from  the  bladder,  has  th' 
appearance  of  a  milk-white,  or  a  yellowish,  or,  through  the  admixture  of  blood,  a  red* 
dish  emulsion;  and  contains  besides  albumin  a  large  quantity  of  tiuely-divided  fat| 
droplets.  This  phenomenon  is  known  as  chyluria.  It  occurs  as  an  endemic  diseas! 
in  certain  tropical  regions  (Brazil,  India,  the  Antilles,  Zanzibar,  Egypt)  where  it  ij 
caused  by  a  parasite,  the  Filaria  Bancrofti,  which  inhabits  the  lymph-vessels  of  thj 
abdominal  cavity  and  there  produces  its  embryos  {Filaria  sanguinis) ;  these,  during  thj 
repose  of  the  patient  in  a  horizontal  position,  swarm  in  great  numbers  in  the  blooci 
and  are  also  found  in  the  chylous  urine.  The  connection  between  the  chyluria  and  thj 
invasion  of  the  lymph-vessels  has  not  yet  been  satisfactorily  demonstrated  by  anatom  | 
cal  investigations;  but  it  is  probable  that  the  chyle-like  fluid  does  not  come  from  tLj 
blood  and  through  the  Ividneys;  but,  as  a  result  of  the  obstruction  in  the  lymph-circi, 
lation,  chyle  escapes  from  ruptured  lymphatics  of  the  bladder  and  mingles  with  tl| 
urine  (Scheuhe,  Grimm).  In  corroboration  of  this  view  is  the  fact  that,  at  autopsy,  tlj 
abdominal  lymphatics  exhibit  marked  dilatation  (Havelburg),  while  the  kidneys  are  bij 
little  clianged;  and  further,  according  to  an  observation  made  by  Ihtrelhtirg,  the  urii! 
obtained  from  the  ureter  showed  no  admixture  of  chyle,  though  chyluria  was  presei 
at  the  same  time. 

The   anatomical  cause    of  the    non -parasitic    chyluria    is   still    u, 
known.  '  I 

Literature. 

{Chylous  Effusions  in  the  Body -cavities  ;  Chyluria.)  ! 

Barg-ebuhr:   Ascites  chylosus.     Deut.  Arch.  f.  klin.  Med.,  51  Bd.,  1893;   Chylose  li 

gi'isse  im  Pleuraraum,  ib.,  54  Bd.,  1895  (Lit.).  j 

Busey:  Am.er.  Jour,  of  Med.  Sciences,  1889.  i 

Edwards:  Chylous  and  Adipose  Ascites.     Ref.  Handb.  of  Med.  Sciences,  1901.         * 
Goetze:  Die  Chylurie,  Jena,  1887.  ' 

Grimm:  Uei)er  einen  Fall  von  Chylurie.     Virch.  Arch.,  Ill  Bd.,  1888. 
Henry:  Case  of  Indigenous  Parasitic  Chyluria.     Med.  News,  1896. 
Hey  decker:  Chyloser  Ascites.     Virch.  Arch.,  134  Bd.,  1893. 
Letulle:  Epanclicments  chyliformes  du  peritoine.     Rev.  de  med.,  1884. 
Lothrop  and  Pratt:  Amcr"!  Jour,  of  Med.  Sciences.  1900.  j 

Predtetschensky:  Europ-lische  Chylurie.     Z.  f.  klin.  Med.,  40  Bd.,  1900. 
Reichenbach:  C;iiy loser  Ascites.     Virch.  Arch.,  123  Bd.,   1891. 
Scheube:  Eiluriukrankheit.     Samml.  klin.  Vortr.  No.    232,    1883;  Parasittire  Hai  • 

chvlurie.     Beitr.  z,  path.  Anat.  u.  z.  klin.  Med. ;   Festschr.   f.    Wagner,    Leipz, 

1SS7. 
Senator:  Chylurie.    Eulenburg's  Realencyklop.,  iv. 
Zune:  I'rines"  chyleuseset  hematochyleuses,  Bruxelles,  1893 

See  also  i^  42. 


CHAPTER  V. 

Retrograde    Disturbances  of    Nutrition   and    Infiltra= 
tions  of  the  Tissues. 

I.  General  Considerations  Concerning  the  Retrograde    Disturbances 
of  Nutrition  and  the  Tissue=Infiltrations. 

§  46.  The  retrograde  disturbances  of  nutrition  are  cliaraeterized  in 
i  general  by  degeneration  of  the  affected  tissue,  often  also  by  diminution  in 
!  size  and  disappearance  of  the  individual  tissue -elements,  ihe  functional  capac- 
1  ity  of  the  tissue  beinc;,  at  the  same  time,  loicered. 

I  The  tissue=inf  iltrations  are  characterized  essentially  by  the  deposit  in 
the  tissue  of  pathological  substances  which  have  either  been  formed  within 
j  the  body  or  introduced  into  it  from  without.  The  functional  capacitg  of 
I  the  part  affected  is  likewise  usually  diminished.  The  infiUration  is  often 
j  only  a  result  of  preceding  degenerative  changes,  or  va^ij  \\^e\t  constitide  the 
I  chief  feature  of  the  degeneration. 

Retrograde  disturbances  of  nutrition  may  affect  the  body  in  its  fully 

developed  state,  or  during  its  period  of  development  and  growth ;  and  in 

I  either  case  may  lead  to  an  abnormal  smallness  of  the  affected  organ  or 

!  tissue.     In  the  former  case  the  diminution  in  size  is  due  to  a  disappear- 

\  auce  of  the  individual  elements  of  the  affected  tissne,  and  is  designated 

atrophy.     In  the  latter  case,  on  the  other  hand,  it  is  dne  to  a  defective 

devehjpment  of  the  affected  organ,  as  shown  by  a  more  or  less  rudimen- 

j  tary  condition  of  its  elements.     If  in  this  way  an  organ  or  a  part  of  an 

organ  wholly  fails  of  development,  so  that  it  is  totally  absent  or  at  least 

is  represented  only  by  its  rudimentary  anlage,  the  condition  is  designated 

agenesia  oi-  aplasia.     But  if  the  development  of  the  affected  part  is  of  a 

certain  degree,  yet  not  reaching  the  normal,  the  condition  is  known  as 

hypoplasia. 

■        The  causes  of  agenesia  and  hypoplasia  are  partly  intrinsic,   and 

i  partly  extrinsic — that  is,  tlu^  stunting  and  iniiu'ifcct  (lc\('l()])in(Mit  of  an 

'  organ  may  depend  as  well  upon  a  pathological  condition  of  its  anlage, 

'  as  upon  external  injurious  influences  which  may  alfect  the  de\<'loping 

part.     The  disturbance  of   development  may  fnrther  affect  either  the 

;  whole  body  or  only  a  part  of  the  same.     In  the  first  case  thore  resnlts  a 

;  dicarf;  in  the  second,  a  stunting  of  indiriduid  parts  or  organs. 

I        Tlie  causes  of  the  tissue=degenerations  and  the  associated  atrophy 

[  are  for  the  gi-eater  jmrt  to  Ixi  found   in   e.\t  liiisic   harnilnl   inllnenees  lo 

which  the  tissues  are   exposed  during  lil'e;  bnl  at  roi)hy  nia.\  also  deitend 

I  upon  intrinsic  conditions.     This  latter  is  pailieularly  tiie  ease  when  the 

(tissues  in  old  age  reach  their  physiological  limit  and  gradually  become 

incapable  of  properly  nourishing  and  preserving  themselves.     In  many 

tissues  a  similar  retrograde  change,  due  to  intrinsic  causes,  occurs  earlier 

in  life,  as,  for  example,  physiologically  in  the  ovaiy  and  thymus. 

As  extrinsic  harmful    influences  which   may  lead  to  degenerations 

1G7 


1 


i 


168  THE  RETROGRADE    CHANGES. 

should  be  considered  all  tliose  agencies  nieutioned  in  Chapter  I.     Dis- 
turbances of  circulation,  lack  of  oxygen  and  food  supply,  and  intoxica-  : 
tions  play  a  very  important  role.     In  the  majority  of  cases  der/enerations 
are  localized,  so  that  Me  may  speak  of  degenerations  of  special  tissues 
or  of  special  organs.     Not  infrequently  the  disturbances  of  nutrition 
are  more  general,  so  that  the  entire  organism  suffers.     Thus  the  picture  ■ 
of  a  general  disease  may  be  produced  by  a  degenerative  or  atrophic  con-  1 
dition  of  the  blood — that  is,  a  diminution  in  the  number  of  red  blood- 
cells  (oligocytha?mia),  at  times  also  a  deficiency  of  haemoglobin  (chloro- 
sis), so  that  a  permanent  condition  of  insufficient  blood-supply  or  a  , 
general  anaemia  is  produced,   the  nutrition  of  the  body  being  corre- 
spondingly imi^aired.  i 
As  the  result  of  a  diminished  ingestion  of  food,  or  of  disturbed  me-  i 
tabolism,  and  of  an  increased  waste  of  the  proteids  and  fats  of  the  body,  I 
there  may  result  a  condition  of  general  emaciation  and  weakness,  often 
associated  with  antemia,  a  wasting  of  the  entire  body,  which  is  designated  ' 
cachexia  or  marasmus.     If  under  such  circumstances  it  appears  likely  ; 
that  certain  substances  are  formed  in  the  body,  which,  when  taken  up  i 
into  the  blood  and  tissue  juices,  cause  a  contamination  or  alteration  of 
these,  the  condition  may  be  spoken  of  as  a  dyscrasia. 

Literature. 

(Disturbances  of  Nutrition.) 

Charcot:  Mn ladies  des  vieillards.     O^uvr.  compl.,  vii.,  1890. 

Demange:  'kt.  clin.  et  anatomo-pathol.  sur  la  vieillesse,  Paris,  1886. 

Le  Gendre:  Troubles  et  maladies  de  la  nutrition.     Traite  de  med.,  i.,  Paris,  1891. 

Halliburton:  (Jheinisclie  Physiologic  und  Pathologic,  Heidelberg,  1893. 

Hoffmann:  Lehrbuch  dcr  Constitutionskrankheiten,  Stuttgart,  1892. 

Jickeli:   Die  L'livoUkomnienheiten  des  Stoffwechsels,  Berlin,  1903. 

Krehl:  Pathologische  Physiologic,  Leipzig,  1904.  j 

Neumeister:  Lehrbuch  dcr  physiologischen  Chemic,  i.,  Jena,  1893.  ! 

V.  Noorden:  Pathologic  des  Stoflfwechsels,  Berlin,  1893.  i 

V.  Recklinghausen:  Pathologic  des  Kreislaufs  u.  der  Eruahrung,  Stuttgart,  1888.       , 

Verworn:  Allgcniciue  Physiologic,  Jena,  1897. 

II.  Death  of  the  Organism,  |i 

§  47.  All  life  comes  sooner  or  later  to  an  end — to  death.  When  this*  ^1« 
occurs  at  an  advanced  age,  without  j)receding  well-defined  symptoms  of  • 
disease,  it  may  be  regarded  as  a  normal  termination  of  life.  This  occur-j 
rence  may  be  attributed,  at  least  in  part,  to  the  fact  that  the  functions  ofi 
certain  organs  necessary  to  the  maintenance  of  life,  become  discontinuedj 
as  the  result  of  intrinsic  causes;  although  in  most  cases  it  is  impossible; 
to  exclude  the  action  of  extrinsic  influenivs  in  helping  to  bring  aboutj 
the  cessation  of  function  of  the  organs  in  question.  1 

When  death  occurs  prematurely— that  is,  at  an  age  earlier  than  thei- 
average  age  of  death  in  man  —and  when  preceded  by  symptoms  of  dis-j 
ease,  it  must  be  regarded  as  a  pathological  phenomenon.  Its  occurrence, 
under  these  (drcumstances  is  for  the  most  part  referable  to  demonstrabk 
extiinsic  infiuences,  but  at  times  may  be  dependent  also  upon  intrinsk 
inheiiled  causes.  It  is  obviously  impossible  to  draw  any  sharp  line  oi 
separation  between  physiological  and  pathological  death. 

Tlie  causes  of  premature— that  is,  pathological — death  are  to  be  fouuc" 
in  those  influences,  which  have  been  discussed  in  Chapters  I.  and  11.  aj; 
the  causes  of  disease.  ! 


I 


DEATH.  109 

An  iudividual  is  to  be  rogarded  as  dead  Avlioii  all  of  Ids  fund  ions 
liavt^  forever  ceased.  J)eatli  is  inevitable  at  that  instant  in  which  one  or 
more  of  the  fnnctions  imperatively  necessary  to  life  has  ceased,  though 
it  is  not  necessary  that  at  that  moment  all  the  functions  should  have 
ceased.  Indeed,  it  often  happens,  that  after  life  is  irretrievably  lost, 
many  oroans  are  still  capal)le  of  performing  their  function,  anil  it  is 
only  after  a  certain  time  that  all  the  organs  die.  The  life  of  the  organism 
pmsra  f/radiui/!;/,  hi/  progressive  cessation  of  the  functions  of  Its  (liferent  or- 
gans, info  the  state  of  death. 

Cessation  of  the  functions  of  the  heart,  lungs,  and  nervous  system 
results  in  an  immediate  death  of  the  entire  organism.  Cessation  of  the 
functions  of  the  intestines,  liver,  or  kidneys  leads  inevitably  to  death 
after  a  certain  length  of  time,  often  measured  by  days.  Destruction  of 
the  sexual  glands  does  not  endanger  the  life  or  health  of  tlie  affected  indi- 
vidual, and  likewise  man  may  also  spare  one  or  more  of  his  organs  of 
special  sense. 

The  occurrence  of  death  is  usually  determined  by  the  last  recogniz- 
able efforts  at  respiration  and  by  the  stoppage  of  the  heart.  With  the 
cessation  of  respiration  it  is  impossible  for  any  organ  to  remain  alive 
after  a  certain  short  period.  The  stoppage  of  the  heart  likewise  makes 
impossible  any  further  nourishment  of  the  tissues,  in  consequence  of 
which  the  central  nervous  system  very  quickly  becomes  unable  to  con- 
tinue its  functions. 

After  death  the  body  may  present  a  variety  of  appearances.  The  aspect  of  the 
external  visible  portions  is  largely  dependent  upon  the  distribution  of  the  l)lood  at  the 
time  of  death.  An  abundant  supply  of  blood  in  the  skin  gives  it  a  blue-red  color, 
anaemia  gives  it  a  pale  color.  Further,  the  preceding  disease  may  alter  the  external 
appearance  of  the  body  in  different  ways. 

Within  a  certain  time  after  death  various  changes  occur  in  the  tissues  of  the  body, 
which  in  part  may  be  regarded  as  the  absolute  signs  of  death.  In  the  first  place  the 
\  temperature  of  the  body  falls,  soxnGiiraes  vix\n(\\y,  iit  other  tunes  slowly,  until  it  reaches 
;the  temperature  of  the  surrounding  air.  It  must  be  borne  in  mind,  however,  that  the 
temperature  at  times  does  not  begin  to  sink  immediately  after  death,  but  first  rises 
somewhat.  The  rate  of  cooling  of  the  body  depends  partly  upon  the  character  of  the 
'l)ody  itself,  and  partly  upon  the  nature  of  its  surroundings.  The  time  required  may 
jvary  from  one  to  twenty-foiir  hours. 

The  coldness  of  the  dead  bodij  is  termed  algor  mortis. 
1  At  the  time  of  death  the  skin  for  the  greater  part  becomes  pale;  but  after  six  to 
twelve  hours,  sometimes  earlier,  blui-sh-red  spots  appear  on  the  skin  over  the  dei)endent 
parts  of  the  body.  These  are  known  as  the  death-spots  or  livores  mortis  (post-nuirtcm 
hypostasis),  and  are  due  to  the  local  accumulation  of  blood  in  the  veins  and  capillaries 
of  the  more  dependent  portions.    They  are  not  found  in  those  parts  of  the  body  suh- 

Bected  to  the  pressure  of  the  weight  of  the  body.  Their  number  and  size  depend  upon 
he  amount  of  blood  in  the  skin  at  the  time  of  death.  Parts  which  have  been  cyanotic 
i  luring  life  may  retain  this  appearance  after  death,  especially  the  head,  fingers,  antftoes. 
,rhe  color  of  post-mortem  hypostasis  is  usually  blue- red;  the  intensity  of  the  color 
•yaries;  in  cases  of  poisoning  with  carbon  monoxide  it  is  a  bright  red. 
I  The  weight  of  the  body  causes  flattening  of  tho.se  muscular  parts  upon  which  it 
i-ests. 

i  Sooner  or  later  there  occurs  a  stiffening  and  contraction  of  the  nni.sclos.  due  to  the 
l^oagulation  of  the  contractile  substance  {Brurcke,  Kiihne).  This  is  known  as  the 
Cadaveric  stiffening  or  rigor  mortis.  It  usually  comes  on  about  four  to  twelve  hours 
ifter  death,  but  inay  occur  almost  immediately  or  as  late  a.s  twelve  to  twenty-four 
iiours.  It  begins  usually  in  the  muscles  of  the  j;nv.  throat,  and  neck,  and  extends 
jrom  them  to  the  trunk  and  extremities.  After  twenty^our  to  forty-eight  liours  it' 
jtsually  vanishes,  but  under  certain  conditions  may  i)ersist  for  several  days. 
',  Rigor  mortis  affects  also  the  sinootli  muscle  fil)ros:  and  the  contraction  of  these 
n  the  skin  gives  rise  to  the  so-called  goose-flesli  of  the  cadaver. 

The  decomposition  of  the  cadaver  begins  with  the  disappearance  of  the  rigor  mortis, 
ts  occurrence  is  shown  partly  by  the  odor  of  putrefaction,  partly  by  changes  of  color 
a  the  skin  and  mucous  membranes,  and  through  changes  in  the  consistence  of  the 


170  THE    RETROGRADE    CHANGES. 

tissues.  The  commencement  and  progress  of  putrefaction  depend  partly  upon  the 
condition  of  the  bodj'-nutrition  and  the  nature  of  the  disease  preceding  death,  partly 
upon  the  conditions  of  the  surroundings,  especially  the  temperature.  Not  infrequently 
putrefaction  may  occur  in  local  dead  areas  of  the  body,  even  before  death  of  the  body  as 
a  whole.  \\'hen  putrefactive  bacteria  are  present  in  the  body,  decomposition  of  the 
cadaver  may  Ijegin  immediately  after  death. 

As  an  early  sign  of  decompositon  there  is  usually  present  a  greenish  discoloration 
of  the  skin,  appearing  first  over  the  abdomen.  With  the  j^rogress  of  putrefaction  the 
unpleasant  odor  and  discoloration  increase;  and  gases  are  formed  in  the  intestine, ; 
later  in  the  blood  and  in  the  tissues,  which  at  the  same  time  become  soft  and  friable. 

Shortly  after  death  the  cornea  becomes  lustreless  and  cluudi/,  the  eyeball  loses  its 
jvominence,  and  dark  spots  appear  in  the  sclera,  which,  gradually  increasing  in  size, 
become  confluent.  These  changes  are  due  to  evaporation  and  decomposition.  If  the 
eyelids  are  not  closed,  the  uncovered  portions  of  the  eyeball  show  the  results  of  drying. 
AVhenever  the  skin  has  lost  its  epidermis  the  exposed  tissues  undergo  desiccation. 

If  all  of  the  phenomena  of  life  be  reduced  to  a  minimum,  there  may  result  a  condi- 
tion of  apparent  death  which  may  be  mistaken  for  real  death.  Though  post-mortem: 
hypostasis,  rigor  mortis,  and  putrefaction  are  unmistakable  evidences  of  death,  these 
changes  may  not  take  place  until  some  time  after  death,  so  that  an  interval  is  left  dur- 
ing which  it  may  under  certain  conditions  be  doubtful  as  to  whether  death  has  actually; 
occurred.  To  ascertain  the  true  condition  under  such  circumstances  it  must  be  de- 
termined by  appropriate  examination  whether  the  heart  still  beats,  whether  respiration 
still  takes  place,  whether  the  blood  still  circulates,  and  whether  the  nerves  and  muscles; 
retain  their  irritability. 

Conditions  which  are  designated  as  apparent  death  occur  under  a  variety  of  cir- 
cumstances, as,  for  example,  in  individuals  suffering  from  cholera,  in  cases  of  cata- 
lepsy, hysteria,  after  excessive  bodily  exertion,  violent  concussion  of  the  central  ner-' 
vous  system,  after  severe  htemorrhage,  suspension  of  respiration  through  hanging' 
strangulation,  or  drowning,  in  certain  cases  of  poisoning,  after  lightning-stroke,  aftei' 
prolonged  exposure  to  cold,  etc.  The  duration  of  this  condition  is  usually  only  short 
but  may  occasionally  be  extended  over  several  hours  or  even  days. 

According  to  the  investigations  of  Fuchs  ("  Ueber  Todtenstarre,"  Zeitschr.  f.  Heii 
kunde,  1900),  the  heart  is  the  first  muscle  to  show  rigor  mortis,  this  organ  bein{i 
affected  at  a  time  (in  animals,  after  three  to  five  hours)  in  which  rigor  mortis  cannot  bil 
demonstrated  in  any  of  the  skeletal  muscles. 


III.  Necrosis. 

§  48.  The  condition  of  local  death,  or  death  of  individual  cells  o: 
groups  of  cells,  is  known  as  necrosis.  As  the  result  of  necrosis  th 
functions  of  the  affected  tissue  are  forever  lost.  , 

The  necrosis  of  a  cell-group  or  of  an  entire  organ  is  only  under  cer 
tain  conditions  immediately  associated  with  recognizable  changes  o. 
structure.  The  slight  histological  changes  which  the  cells  undergo  dur. 
ing  their  death  do  not  always  permit  us  to  determine  with  certainty  th 
exact  moment  of  cessation  of  life;  nor  does  the  macroscopic  appearanc' 
of  the  visible  portions  of  the  body  always  inform  us  when  a  portio: 
thereof  becomes  necrotic. 

Necrosis  is  therefore  evident  upon  anatomical  investigation  only  whe 
certain  changes  in  structure  have  occurred,  either  coincidently  with  tL 
death  or  substM^nently  thereto.  Necrosis  is  shown  immediately  by  hist( 
logical  changes  only  in  the  case  of  the  action  of  a  limited  number  of  ii' 
jurious  agencies;  in  all  other  cases  the  necrosis  is  followed  by  sue 
changes  after  a  longer  or  shorter  interval.  According  to  the  nature  < 
the  sub.sequent  tissue-changes  it  is  possible  to  distinguish  different  vari 
ties  of  necrosis. 

Ilistologically  the  necrosis  of  a  cell  is  shown  in  the  first  place  by  tl 
disi)itrf/rafioH  and  disappearance  of  the  nucleus,  whereby  the  chromatin 
the  coll — that  part  taking  nuclear  stains — forms  small  clumps  and  gra 
ules  which  at  times  pass  out  from  the  nucleus  into  the  cell-protoplasi. 


I 


NECROSIS. 


171 


where  they  become  dissolved  and  disappear  (l-ori/orrIu'xi,s).  At  othei- 
times  the  nucleus  before  its  disappearance  shows  fiiffns  of  shrinking,  and 
iu  this  condition  takes  the  nuclear  stain  moie  deeply  tluui  under  normal 
conditions  (pi/Jxnofiis).  Iu  other  cases  the  uncleus  retains  Hs  form  hut.  loses 
its  staininff  power  with  iiuelear  stains,  and  then  dissolves  and  disap])ears 
(Fig.  35,  c,  d),  so  that  iu  Avell -fixed  and  stained  preparations  no  trace 
whatever  of  the  uucleus  can  be  found  (Icarj/oli/si.s).  Thus,  for  exanii)le, 
in  an  an;emic  infarct  of  the  spleen  or  kidney  caused  by  artci'ial  embolism 
the  imclei  of  tiie  spleen  and  kidney  cells  are  lost  very  soon  after  the 
death  of  the  tissue  (Fig.  36,  e,  d,  f,  g).  At  the  same  time  the  affected 
area  becomes  strikingly  pale,  cloudy,  yelloAvish-white,  or  cream-colored; 
so  that  the  occurrence  of  the  necrosis  may  be  recognized  l)y  the  naked 
eye. 

The  lirotoplasm   of  the  dying  cells  sooner  or   later  also   undergoes 

changes,  which,  according  to  the  mode  of  death,  may  in  some  cases  begin 

before  the  cells  die,  or  in  others  may  take  place  only  after  the  cells  are 

dead.     The  kind  of  change  is  dependent  upon  tlu-ee  factoi's:  the  natuie 

of  the  cells  themselves,  the  character  of  the  destiuctivc  intluence,  and 

the  amount  and  character  of  the  fluids  suiTOunding  and  infiltrating  the 

I  cells.     Amoeboid  cells  usually  assume  a  globular  form  after  death.     Deli- 

I  cate  and  only  slightly  modified  cell-bodies,   rich  in  protoplasm,  often 

I  become,  before  or  after  death,  markedly  grannlar,  less  frequently  homo- 


\  and  Fig.  36,  e).  Through  the 
!  taking-up  of  fluid  the  protoplasm 
;  or  even  the  nucleus  may  become 
\  swollen  and  show  dro2)S  of  fluid 
\  (vacuoles) ;  and  this  may  lead  to 
I  breaks  in  the  continuity  of  the 
'  protoplasm  (2)lasmoschisis).  Not 
1  infrequently  as  a  result  of  plas- 
;  moschisis  7>o/f/o».s  of  theeell  man 
[  he  extruded  or  cut  off  hij  const rie- 
\tion.  The  ultimate  end  of  all 
I  these  changes  is  the  disintegra- 
\tion  of  the  protoplasm  and  the 
\nucleus  into  granular  masses,  this 
i  process  being  often  accompanied 
I  by  a  formation  of  fat. 
I  Cells  which  normally  undergo 
!a  marked  transformation,    as  is 

the  case  with  cells  showing  coi - 
inification,  usually  present  less 
i striking  changes;  yet  even  these 
{may  swell  and  finally  become  dissolved.       Tin-  nioi  plKtlogical  changes 

iu  dead  cells  are  the  least  pronounced  when  the  dying  cells  become 
more  condensed  and  dry  (insjnssation).  In  this  case  the 'cells  only  become 
isinaller,  yet  it  is  often  seen  that  aftei' the  loss  of  the  nucleus  the  cells 
I  become  changed  into  lumpg  )nasses. 

!  The  injurious  influences  which  may  give  I'ise  to  necrosis  may  be 
'divided  into  five  jrroups.  The  liist  two  include  those  which  destroy  tlie_ 
Itissne  directly — mechanical   and  chemical  forces.      A   third  grouj)  ()f 

injurious  influences  comprises  those  of    a  thermal    character,      flie 

elevation  of  the  temperature  of  a  tissue  to  r)4'=-6S    ('.  f(»r  any  length  of 


Fig.  35.— Necrosis  of  the  epithelium  of  the  urinary 
tubules  In  icterus  pravis.  (Miiller's  fluid,  pentian 
violet.)  a.  Normal  convoluted  tubule:  h,  ascendinK 
l)(iriioii  i.f  the  loop;  c,  convoluted  tubule  with  necrotic 
cpillitliiiiii;  (I,  convoluted  tubule  with  only  a  part  of 
its  t|iithiiiniii  necrotic;  e,  normal  stroma  with  blood- 
vesM'ls.    :•.  :i<K). 


172  THE    RETROGRADE    CHANGES.  I 

time  leads  to  its  death.     Higher  temperatiTres  act  more  quickly.     Re-' 
frigeration  to  low  temperatures  likewise  can  be  borne  but  a  short  time.') 
A  fourth  gi-oup  is  caused  l)y  infection  with  animal  or  vegetable  para- 
sites.    A  fifth  group  is  caused  l»y  a  cessation  of  the  supply  of  nourish- 
ment and  oxygen  to  the  tissues,  and  is  known  as  anaemic  necrosis  oi 
local  asphyxia  (Fig.  36).  • 


fivr* 


a  (I  f  ^  C 

Fig.  36.— From  the  edge  of  an  anagmic  infarct  of  the  kidney.  (Muller's  fluid,  hsematoxylin,  and  eosin. 
O,  Normal  kidney  tissue ;  Oj,  normal  kidney-tubules  with  stroma  infiltrated  with  leucocytes;  b,  norms 
glomerulus ;  c,  necrotic  tissue  without  nuclei,  showing  granular  coagula  in  the  tubules ;  d,  necrotic  swoUe 
glomerulus  with  few  nuclei ;  c,  tubules  without  nuclei  in  a  stroma  still  containing  nuclei ;  /,  necrotic  tissu 
with  cellular,  y,  with  ha3morrhaglc  infiltration.    X  50. 

All  those  factors  which  seriously  affect  the  circulation  within  any  par, 
and  lead  to  a  stoppage  of  the  blood-supjily— such  as  thrombosis,  embolism' 
closure  of  a  vessel  as  a  result  of  continued  abnormal  contraction,  diseaS'! 
of  the  vessel-walls,  or  ligation,  pressure  on  the  tissue,  inflammation,  hoem 
orrhage,  etc.,  may  lead  to  necrosis  of  tissue.  Not  only  a  permanen 
cessation  of  the  circulation,  but  also  a  temporary  stoppage  of  the  sam' 
lasting  beyond  a  certain  time,  leads  to  the  death  of  the  affected  tissue 
Whether  or  not  haemorrhage  occurs  in  such  cases  is  immaterial,  as  wa 
stated  in  §  44,  and  influences  only  the  appearance  of  the  affected  part 
Hwmorrhagic  infarction  has,  therefore,  precisely  the  same  significance  a 
an  anccmic  necrosis  associated  nith  hcemorrhage. 

When  death  follows  quickly  upon  the  action  of  an  injurious  agent 
it  is  spoken  of  as  direct  necrosis.  When  it  occurs  slowly  and  is  pre. 
ceded  by  different  tissue-degenerations  it  is  designated  indirect  necrosi 
or  necrobiosis. 

Mechanical,  chemical,  thermal,  and  infectious  sources  of  injury,  a 
well  as  aiia-mia,    may   act   coincidently,    or   separately,    one   after  th 
other.     When   the   tissue  is  damaged   by   any  one   of  the   first-name 
group   of    injurious    influences,   the   blood    itself    very  often  suffers 
change,  which  leads  to  stasis  and  coagulation  in  the  capillaries,  as  we 


NECROSIS.  17  A 

as  in  the  veins  and   artci'ies,  and   in   Ihis  ^\a^    llic  cii-cnlal  ion    jiiay    ln' 
arrested. 

Wliether  or  not  a  iiiven  injuiy  will  cause  necrosis  of  the  tissue  de- 
pends, not  only  upon  its  nature  and  se\eiity,  but  also  chielly  u]>on  the 
condition  t)f  the  tissue  at  the  time  of  the  injui-y.  A  tissue  whose  \ital- 
ity  has  already  been  lowered  as  the  result  of  louji-continned  disturbances 
of  circulation,  general  marasmus,  hydriemia,  changes  in  the  comi»osit ion 
of  the  blood,  etc.,  dies  more  easily  than  when  in  ;i  noi-nnil  condition.  Jn 
severe  ciusesof  typhoiclfever  relatively  slight  pressure  on  the  tiochant^Ms, 
elbows,  sacrum  or  heels,  etc.,  may  suflice  to  bring  about  a  gangienous 
necrosis  of  the  skin  and  subcutaneous  tissues.  kSuch  foi-nis  of  necrosis 
are  knt>wn  as  marasmic  necrosis  or  marasmic  gangrene,  and  as  decu- 
bitus or  decubital  necrosis. 

The  course  of  necrosis— that  is,  the  tissue-changes  resulting  from  the 
death  of  cells — is  lU'pendent  upon  the  charaeter  of  the  allectetl  tissue,  its 
location,  the  manner  of  its  death,  anil  the  cause  of  the  necrosis.  Further, 
the  amount  of  lymph  and  blood  in  the  tissue,  and  the  opportunity  atforded 
for  the  access  of  air  and  putrefactive  organisms,  also  exert  a  very  im- 
portant influence.  Tissue-changes  which  preceded  the  necrosis,  such  as 
fatty  degeneration,  inflammation,  luemorrhage,  etc.,  are  also  of  signifi- 
cance in  determining  the  character  of  the  necrosis. 

As  the  result  of  the  necrosis  of  a  certain  tissue=area,  there  always 
develops  an  Injiammationof  greater  or  less  intensity  int/ie  surrounding  tissues 
(Fig.  36,  /).  This  reactive  inflammation  is  most  marked  "syhen  the 
necrotic  area  becomes  gangrenous.  Through  the  fornuition  of  an  inllam- 
matory  zone  the  necrotic  area  becomes  marked  off  from  the  surrounding 
tissue,  and  is  isolated  or  sequestrated ;  this  process  is  si)oken  of  as  a  se- 
questrating or  limiting  inflammation,  and  the  dead  area  thus  shut  off  is 
called  a  sequestrum.  A  more  detailed  descrii)tion  of  these  inilamniatory 
processes  will  l)e  found  in  Chapter  YII. 

Five  chi<'f  sequelae  of  necrosis  may  be  distinguished :   1 .   The  dead  tis- 

i    sue  may  be  remo\ed  l)y  aljsorptiun,  or  may  be  cast  of  from  the  surface,  and 

j    its  place  taken,  hg  nonnal  tissue  {regeneration).     2.   The  dead  tissue  is  simi- 

)    larly  remo\ed,  but  instead  of  the  normal  tissue  being  restored,  the  defect 

is  filled  wholly  or  in  part  by  the  formation  of  connective  tissue,  the  so- 

I    called  cicatricial  tissue.     3.   The  necrotic  tissue  is  cast  off  oi-  li(pietied, 

i    the  defect  is  not  tilled  in.  and  there  lemains  an  »/<ry.     Should  this  heal 

I    without  regeneration  of  the  lost  tissue  there  remains  a  ihj'ect.     4.   The 

j    necrotic  tissue  is  partly  absorbed,  but  a  jjortion  lemains  as  a  sequestrated 

necrotic  ma.s.s  which  not  infre(piently  later  becomes  caleifled v\w\  su rrou nded 

by  a  connrrfi re-tissue  cajjsute.     5.   The  lifth  sequela  of  necrosis  is  r//.s7-/o/- 

mation.     The  necrotic  area  becomes  encapsulated  by  connective  tissue, 

the  dead  tissue  becomes  absorbed  and  is  replaced  wholly  or  in  ]>art, 

usually  at  the  peri])hery,  by  new  tissue,  or  it  may  be  liquefied,  and  the 

space  filled  with  fluid,  forming  a  cyst.     This  seiiuela  of  necrosis  occurs 

most  fre<iuently  in  the  brain. 

By  many  writers  there  is  recojrnized  besides  these  forms  of  necrosis  an  especial 
group  designated  as  neuropathic  necrosis,  tliat  is,  a  necrosis  resulting  fnjtn  a  lesion 
of  the  central  or  peripheral  nervous  system.  liy  some  the  essseiitial  cjiiise  of  such 
necrosis  is  referred  to  a  lesion  of  the  trophic  nerves,  wliile  others  refer  it  to  (listurl)ances 
of  circulation,  continued  pressure,  and  mechanical  injun'  of  ana-sthetic  and  paralyzed 
portions  of  the  body.     According  to  observations  thus  far  made  upon   men,  as  well  as 


174 


THE   RETROGRADE    CHANGES. 


upon  experiments  in  animals,  external  injuries  and  disturbances  of  the  circulation 
play  the  most  imj^ortant  role  in  the  production  of  this  form  of  necrosis,  and  can  never 
be  wholly  excluded. 

The  time  required  to  kill  tissue  by  the  shutting-off  of  the  circulation  varies  with  ; 
the  different  tissues.  Ganglion-cells,  kidney  epithelium,  and  liver-cells  die  in  two  i 
hours,  while  surface  epithelium  and  connective  tissue  may  live  for  twelve  hours  ov\ 
longer.  Epidermis  under  certain  conditions  may  remain  alive  for  a  number  of  days,  i 
and  still  retain  its  power  of  proliferation  (see  Transplantation). 

Karyorrhexis,  karyolysis,  and  tissue  liquefaction  occur  also  in  putrefaction. 
Tissue  preserved  under  aseptic  precautions,  and  protected  from  bacteria  in  moist  , 
chambers  at  the  body-temperature,  also  loses  its  nuclei.  Liver-tissue  shows  this 
change  most  rapidly  and  completely,  the  tissues  of  the  spleen  and  kidney  more  slowly  \ 
and  less  completely,  so  that  all  nuclei  may  not  have  disappeared  after  eight  to  fourteen  i 
days.  The  disappearance  of  the  nucleus  occurs  only  in  the  presence  of  a  relatively ! 
abundant  supply  of  fluid,  and  may  be  prevented  by  desiccation  of  the  tissue.  I 


Fig.  37.— Coagulation-necrosis  in  the  interior 
of  a  greatly  swollen  mesenteric  lymph-gland, 
from  a  case  of  typhoid  fever.  (Alcohol,  flbrin 
stain.)  Network  of  fibrin  between  the  necrotic 
cells.     X  300. 


§  49.  Accordiug  to  the  various  coiiditious  in  which  the  tissues  may 
be  found  after  they  have  died,  four  chief  forms  of  necrosis  maybe  distin- 
guished :  coagulatio7i-necrosis,  caseation,  Uquef action-necrosis,  and  gangrene. 
Coagulation=necrosis  (Weigert,  Cohnheim)  is  characterized  by  the 
occurrence  of  coagulation,  either  extracellular,  in  the  fluids  about  thei 

cells;  or   intracellular,    in   the   latter' 
case  leading  to  peculiar  changes  with- 
in the  cells.  : 
As  coagulation-necrosis  with  extra-  \ 
cellular  coagulation  may  in  the  first' 
place  be  regarded  both  the   intia- 
vascular  (Figs.  14-17)  and  the  ex- 
travascular  coagulation   of  the  blood,  j 
inasmuch  as  this  phenomenon  mayi 
be   regarded    as    the   death   of  thej 
blood;  and  in  fact  a  destruction  oi 
cells  does  occur.     Further,  there  may 
be  considered  as   belonging  to  this 
class  the  various  forms  of  coagulatior 
which  occur  in  inflammations,  partlj' 
on  the  surface  and  partly  in  the  in 
terior  of  the  tissues  (see  Chapter  VII.);  and  which  are  characterized  bj 
the  formation,  in  some  cases,  of  stringy  fibrin  (Fig.  37),  in  other  cases 
by  the  formation  of  granular  or  hyaline  masses  of  coagula. 

Intracellular  coagulation  occurs  when  dead  cells  or  cell-products  ar« 
infiltrated  with  a  fibrinogen-containing  lymj)h.  The  cells  lose  their  nu 
clei,  present  either  a  granular  (Fig.  35,  c,  d,  and  Fig.  36,  c,  d,  e)  or  ; 
hyaline  lumpy  appearance.  They  remain  in  this  condition  for  a  certai]| 
time  and  then  break  down  into  granules  and  become  dissolved.  i 

This  phenomenon  is  most  frequently  observed  in  ana?mic,  toxic,  an(| 
thermal  tissue-necroses,  as  for  example,  in  anaemic  infarcts  of  the  kidne; 
(Fig.  30)  and  of  the  spleen,  also  in  many  inflammations  which  are  assol 
ciated  with  marked  infiltration  of  the  tissues  (Fig.  37),  due  to  exudatio- 
from  tlie  blood-vessels.  In  the  necrosis  of  striped  muscle,  which  is  O; 
very  fiequent  occurrence  in  typhoid  fever,  the  contractile  substauc; 
acquiies  a  hyaline  waxy  appearance  and  breaks  up  into  hyaline  lump 
(Fig.  38,  h). 

The  necrotic  tissue  of  anaemic  infarcts  looks  pale  yellowish-white,  c 
cream-cohued.  Muscles  containing  many  dead  fibres  in  a  state  of  hyf 
line  coagulation  are  pale  red,  and  of  a  dull  lustre,  resembling  fish-flesl! 


COAGILATIOX-XECHOSIS :    CASEATION. 


Fig.  38.  — Hyaline  necrosis  or  waxy 
def?eneration  of  niusele,  from  a  ca-se  of 
typhoid  fever,  a.  Normal  imiscle-llbre ; 
1>,  degenerated  fibres,  which  liave  broken 
up  into  liyaline  lumps ;  c,  cells  lying  with- 
in the  sarcoleniina ;  d,  connective  tissue 
infiltrated  with  cells.     X  250. 


Inflamed  tissues  umlerooing-  coa.uulatioii    necrosis  aiv  likewise  clondy, 
opaque,  and  jjrayish-whilo;  but  the  color  may  undergo  marked  chanj^^es 
through   the  admixture   of  blood  or  the 
imbibition  of  bile,  as  in  the  intestine,  for 
example. 

The  structure  of  a  tissue  which  is  the 
seat  of  a  coagulation -necrosis,  may  still 
be  clearly  recognized  if  only  the  more  del- 
icate parts  have  been  destroyed.  When 
all  parts  have  been  changed,  the  entire 
tissue  may  be  converted  into  a  structure- 
less, hyaline,  or  granular  mass,  containing 
no  nuclei  or  but  few.  This  change  takes 
place  very  often  in  the  necrosis  of  in- 
flamed tissues  which  are  infiltrated  with 
exudate.  Through  the  proper  treatment 
of  preparations  there  may  be  frequently 
demonstrated  in  these  necrotic  areas  an 
intercellular  stringy  fibrin;  this  is  seen 
occasionally  in  antemic  infarcts,  but  more 
often  in  inflammatory  tissue  -  necroses 
(Fig.  37). 

Caseation  is  a  form  of  necrosis  closely 
related  to  coagulation-necrosis,  and  is 
characterized  by  either  a  hard  or  a  soft 

cheesy  api^earance  of  the  necrotic  area.  In  the  first  case  the  dead  tissue 
is  like  firm,  yellowish- white,  hard  cheese,  or  similar  to  raw  potato;  in 
the  second  case  it  is  white,  soft,  sometimes  dry,  sometimes  moist,  an<l 
not  infrequently  resembling  thick  cream. 

Typical  caseation  occurs  most  frequently  in  tuherdrs  and  rei>resents 
the  characteristic  end  of  the  retrogressive  changes  in  this  condition.     It 
also  occurs  in  syphilitic  granulomata  and  in  very  cellular  tumors;  in- 
flammatory exudates  may  also  become 
changed  into  cheesy  masses. 

The  process  of  caseation  of  cellular 
tissues,  which  is  a  characteristic  of  tu- 
berculous granulations,  takes  place  grad- 
ually, and  is  therefore  to  be  regaided  as 
a  form  of  necrobiosis.  The  cells  are 
changed  successixcly  into  non-nucleated, 
homogeneous,  lumiiv  masses,  which  later 
disintegrate  and  break  up  into  a  gran- 
ular mass  (Fig.  39,  a,,  a).  At  the  same 
time  with  these  changes  there  often  ap- 
pears between  the  cells  a  liyaline  sub- 
stance, sometimes  foi'ining  a  framework 
around  the  cells  or  at  otln-r  times  more 
lumpy  or  graniilai",  and  til)riii-like — the 
so-called  ''  I'lhrinoid  sKhsfaiirr."  Ti/pic(if 
fhrillatrd  fibrin  (Fig.  40,  a)  staining  dee]) 
blue  with  Weigert's  fibrin  stain  is  often  also  present.  It  may  therefore 
be  assumed  that  both  substances  represent  coagulation-products  of  a 
fluid  which  has  escaped  from  the  blood-vessels. 

Through  jirogressive  cleavage  and  disintegration  of  the  (lend  cells, 
the  fibrinoid  substance,  and  the   fibrin,   th»,'  dead   tissue    is    iilliuiately 


m^^^^sk-m: 


Fig.  39. -Tissue  from  a  partly 
tuberculous  focus,  containing  bacilli.  (Al- 
cf)hol,  fuchsin,  aniline  blue.)  a.  Granular; 
«!,  lumpy  masses  of  cheesy  material:  h, 
flbrocellular  tissue;  c,  partly  necrotic  giant- 
cell  containing  tubercle  bacilli ;  d.  bacilli 
in  the  cellular  tissue ;  e,  bacilli  in  necrotic 
"*»"«;   /,   bacilli  enclosed    within  cells. 


176 


THE    RETROGRADE    CHANGES. 


changed  into  a  finely  granular  mass,  in  which  no  traces  of  the  original 
structure  can  be  percei\  ed. 

The  cheesy  metamorphosis  of  the  fibrino-cellular  exudate,  which  is 
found  especially  in  the  aheoli  of  the  lungs  in  the  neighborhood  of  tuber- 
cles, is  brought  about  similarly  by  the  disapx)earaiice  of  the  nuclei,  and 
the  disintegration  of  the  cells  and  fibrin  into  a  non-nucleated  granulai; 
mass.  i 

The  granules  of  the  soft  cheesy  masses  in  tuberculous  and  non-tuber! 
culous  foci  are  chiefly  albumin  granules,  more  rarely  fat-droplets.  Th( 
ultimate  fate  of  such  masses  may  be  partly  liquefaction  and  imltaceoxu, 
soffoiinf/,  i)artly  ahsorption,  and  partly  desiccation  and  eulrification. 

Colliquation  or  liquefaction=necrosis  is  charaeterizcd  especially  \>\ 
the  fact  that  the  necvoiic  parts  become  dissolved  in  the  Jinids  present  in  th 


\ c^  fo^  %  ^ ^  *  m&m^^',i^-^^  - "     '     'A4— 


Fig.  40.— Fibrin-containinp  tubercle   from  the  lunp.     (Alcohol,  haematoxylin,  Ubrin  stain.)    a,  Fibni. 
b.  Riant-cell ;  c,  cellular  portion  of  the  tubercle.     ;<  IMI. 

tissues.  The  dissolution  may  be  accomplished  by  swelling  and  liquefju 
tion,  as  well  as  by  a  breaking  up  of  the  tissue-elements,  or  through 
combination  of  these  processes.  Thus,  for  example,  in  burns  of  the  sec 
ond  degree  the  cells  of  the  epidermis,  which  have  been  killed  by  tL 
heat,  with  the  exception  of  the  horny  layer,  become  dissolved  in  the  flui; 
exuding  from  the  papillai  (Fig.  41,  d,  f).  In  the  case  of  amemic  infarc 
of  the  brain  the  necrotic  brain-substance  undergoes  softening  with  tl 
formation  of  drops  and  granules,  and  becomes  converted  into  a  milk;. 
])ultaceous  mass  in  which  the  products  of  the  destruction  of  the  braii 
ti.ssue  disintegrate  into  smaller  and  smaller  particles,  which,  either  fn 
or  enclosed  within  cells,  become  absorbed  or  comi:>letely  dissolved.  I 
suppurative  processes  of  the  tissues,  which  occur  very  frequently  i 
purulent  inflammations,  the  necrotic  tissue  is  dissolved  in  the  fluid  va 
cular  exudate  containing  pus  corpuscles. 

Xecrosed  areas  in  t  lie  mucosa  of  the  stomach  become  dissolved  thi'ouf; 
the  digestive  action  of  the  gastric  juices. 

Coayidation  and  liquefaction  may  not  infrequently  follow  or  prece< 


i 


AUTOLYSIS. 


177 


each  other.  For  exaiupk^,  the  products  of  coiigulation  in  an  iiillanicd 
area  may  agaiu  become  dissolved.  In  gangrenous  l)lel)s  produced  by  the 
dissolution  of  ei)ithelial  ceils,  there  may  occur  a  coagulation,  the  prod- 
ucts of  which  are  later  agaiu  dissolved.  Necrotic  ft)ci  arising  in  the 
course  of  inllammatious  or  in  granulonuita  very  often  at  a  hiter  stage 
become  liquelied. 

In  the  case  of  both  tlu^  eoagnlntion  and  the  liqiirfartinn  of  tissues  the 
process  tlepcnds  essentially  ui)on  the  action  of  ferments,  which  arc  com- 
bined in  part  with  living  i)rotoplasni  and  in  i)ail  aie  contained  in  the 
(lead  tissue.  The  liquefaction  of  tissue  by  tissue-ferments  is  designat<'d 
autolysis.  The  actiou  of  the  autolytic  ferments  tak«'s  i)lac<'  also  in  })oi- 
tious  of  tissue  that  luive  been  kei)t  aseptic  outside  of  the  body,  or  pre- 
served in  antiseptic  fluids  (chloroform  water)  that  inhibit  the  growth  of 
bacteiia.  Theie  occurs  a  li(pU'faction  of  the  tissue  with  the  formation  of 
various  products  of  decompositiou. 

The  cliauges  described  above  as  occurring  in  dead  or  dying  tissues  are  not  the  only 
ones  whicli  take  place  during  tissue-destruction.  They  are  only  the  chief  types  which 
occur  in  the  course  of  a  relatively  rapid  necrosis.  Many  of  the  tissue-degenerations 
described  in  the  following  paragraphs  also  lead,  not  infrequently,  to  ultimate  death 
of  the  tissue,  and  consequently  they  must  be  regarded  as  belonging  to  the  processes 
classed  as  tissue-necrobiosis.     Granular  degeneration,  fatty  degeneration,  mucous  degen- 


^■^Z 


Fir.  41.— Blister  of  cat's  paw.  caused  by  hot  sealine-wax.  (Alcohol,  carmine.)  n.  Homy  layer  of  the 
•pldermis:  b,  rete  Malpi^hii  -,  c,  nonnal  papilla;  d,  swollpn  epithelial  cells  whose  niicli-i  are  in  part  visible, 
'ind  in  part  have  disappeared ;  r.  epitheliiil  ii-lls  \\in<i  liitwi-rii  the  piipillie,  the  upper  ones  swollfii  and 
l-lonirated,  the  lower  on.-spivs.Tvcd;  /',  total  li(|iii-fiHtl.in  of  tli.- i-piihclimn  :  <;.  swoll.'n  cells  of  ih.' Ini.-r- 
liapillary  cell-ma.sses,  which  have  Inst  tlicir  nuclei;  //.  a  similar  ccll-ninss  which  lias  liccii  conipl.-t.-lv 
llestroyed.  and  raised  from  the  hasement-mciuhrane,  hv  the  coayiilatc(|  subepithelial  exudate  /,■ ;  i,  llatlened 
jiapillar>-  lx)dy  infiltrated  with  cells.     X  150. 


ration,  and  hydropic  degeneration  often  end  in  tlie  destruction  of  ceils;  and  the  same 
esultmaybe  reached  in  the  case  of  hyaline  and  amyloid  degeneration  of  tlie  connective- 
issue,  in  tliat  not  onlv  the  [rrotmd-su'bstance  of  the  tis.sue  is  permanently  altered,  l)ut 
lie  cells  of  the  afleeted  tissue  also  die. 

According  to  the  investigations  of  Srhmaus  and  Alhtrrfit,  kidney  epithelium  soon 
•ecomes  invisible  in  water,  salt  solutions,  and  diluted  alluilies.  in  tlitit  tiu'  cells  become 
wollen  or  dissolve.  Epithelial  cells  whieli  have  become  graiiiiiar  tlwougli  iina-mic 
■ecrosis  retain  their  granultir  structure  in  tlie  solutions  named.  Tills  may  be  l!il<cn 
Is  a  proof  tliat  coagulation  has  occurred  witli  tlie  formation  of  lirm  bodies,  not  soluble 
p  dilute  acids,  all<alies,  and  neutral  salts,  out  of  elements  occurring  originally  in  the 
[ells  in  a  fluid  state. 

I  The  number  of  enzymes  contained  in  the  tissue-cells  is  very  great.  IIofmriMcr 
Iscribes  to  the  liver-cells  at  least  ten.  In  tlie.se  cells  iliere  sniclv  occur  a  proteolvlio 
i  12 


178  THE    RETROGRADE    CHANGES. 

enzyme  (trj-ptase)  ■whicli  disintegrates  the  albumin-molecule,  a  ferment-splitting  nu. 
cleo-proteoid  and  nucleiuic  acid,  and  a  diastatic  ferment  changing  glj-cogen  into  sugar. 
Proteolytic  enz3'mes  occur  probably  in  the  most  varied  tissues,  perhaps  in  all  {Sal- 
koicski ,1.  c).  At  the  present  time  we  do  not  know  whether  they  are  active  under 
physiological  conditions,  or  whether  they  are  present  in  the  cells  only  as  inactive  pro- 
ferments or  zymogen,  which  first  become  active  during  or  after  the  death  of  the 
cells  under  the'influence  of  a  "kinase."  In  order  to  decide  these  ciuestions  it  would  be 
necessary  (So/A-ou'sAO  to  show  accurately  the  characteristics  of  the  products  of  autol- 
ysis of  different  organs  and  to  seek  out  the  specific  autolytic  products  also  in  the  cor-! 
responding  organs  of  freshly  killed  animals.  A  splitting  of  nuclein-substances  by 
ferments  during  life  is  sliown  positively  by  the  fact  (Salkoicski)  that  purin  bases,  the 
specific  products  of  nuclear  disintegration,  can  be  demonstrated  in  all  fresh  organs. 

§  50.  Under  the  name  of  gangrene  may  be  classed  those  forms  of 
necrosis  in  which  the  tissue,  partly  through  exposiTre  to  the  air,  partly 
through  the  agency  of  bacteria,  suffers  changes  which  are  similar  in  ap-i 
pearance  to  those  occurring  in  burned  tissues.  If  necrotic  tissue  through 
exposure  to  the  air  loses  irs  water  by  evaporation  and  becomes  dry,  the 
condition  is  designated  dry  gangrene  (ganffrcena  sicca)  or  mummifica- 
tion. When  the  dead  part  remains  moist,  the  terms  moist  gangrene' 
{gungrcEua  luunida)  or  spliacelus  may  be  applied.  If  through  the  agency! 
of  bacteria  there  occurs  ia>  foul -smelling  putrefaction,  the  condition  is  known' 
as  a  putrid  gangrene  {gangrcena  fcetida).  Development  of  gas-bubbles; 
as  a  result  of  the  putrefactive  changes  leads  to  emphysematous  gan=' 
grene  {gangrcena  emphysematosa). 

Moist  gangrene  and  putrid  gangrene  are  in  general  identical,  since 
bacteria  can  develop  only  in  moist  tissues.  Nevertheless  a  dry  gangrene; 
is  not  infrequently  a  putrid  gangrene,  since  bacteria  may  develop  in  the; 
tissue  before  drying  takes  place.  Dry  gangrene  may  also  develop  from; 
a  moist  gangrene,  or  through  the  absorj)tion  of  water  become  changed^ 
into  the  latter. 

When  the  dead  tissue,  in  either  mummification  or  moist  gangrene, 
contains  a  large  amount  of  blood,  it  appears  black,  dark  brown,  oi' 
greenish-black  in  color,  and  is  then  called  black  gangrene.  If,  on  the: 
other  hand,  the  dead  tissues  are  ansemic,  the  condition  is  sometimes 
spoken  of  as  white  gangrene,  although  there  is  more  or  less  discolor 
ation  of  the  dead  part,  so  that  the  expression  is  often  inappropriate. 

In  the  case  of  gangrene  of  superficial  parts  of  the  body,  there  may  br 
distinguished,  according  to  the  temperature  of  the  dead  part,  a  cold  aiK 


F:o.  42. — Dry   Kansrene  of  the  tois,  due   to   calririrali<in,   narrowiiij;,   and   obliteration   of   tin- 
arteries. 

a  irarm  or  hot  gangrene,  the  latter  designation  being  used  when  the  g;ui 
grenous  area  is  kept  warm  by  the  blood  flowing  through  the  ueighboriii. 
tissues. 

Gangrene  may  be  caused  by  external  injuries,  heat,  cold,  corrosive;- 
crushing,  pressur(\  infection,  etc.,  as  well  as  by  disturbances  of  the  cii 
dilation. 


GANGRENE.  179 

Gangrene  due  to  disturbance  or  arrest  of  the  circulation  oceui-s  not 
infivqiu'iilly  ill  old  people  (sini/c  (/<iu(/rc)if),  iii\  ttlxiiii;-  \\\v  cxtreiiiities, 
]>:irti('ul:uly  the  toes,  feet,  and  legs.  It  is  iisiuUly  oi"  the  dry  Viirieiy, 
and  is  dependent  i^artly  upon  general  disturbanees  of  the  eirculatiou  and 
])ai'tly  ui)on  disease  of  the  arteries  of  tlie  extremities  (caleitication,  ossi- 
lication,  thiekening  of  the  intinia,  thrombosis,  (Mnbolism)  (l^^ig.  42). 
The  dying  i)ar1s  ai>pear  blnish-black  as  a  resnlt  of  the  venctus  stasis. 

Gangrene  from  cold  atfects  ehietly  the  tii)s  t)f  the  extremities,  nose, 
and  ears,  and  is  eharaeteii/ed  by  changes  similar  to  those  described  above. 
Gangrene  from  heat  is  con  lined  to  the  area  directly  affected  by  the  heat. 
Pressure=gangrene  or  decubitus  (&r(7-s'o;r)  occurs  in  niarasmic  indi- 
viduals, most  frequeutly  upon  the  sacrum  and  the  h(;els,  both  of  which 
regions  are  exposed  to  pressure  when  the  individual  lies  upon  his  back. 
The  bedsore  begins  with  the  formation  of  bluish-red  si)ots,  within  whose 
area  the  tissue  dies,  and  through  the  agency  of  bacteria  undeigoes  de- 
composition and  finally  disintegrates.  The  gangrenous  ai-ea  may  be  of 
large  extent,  especially  when  over  the  sacrum  ;  the  lunu^  may  be  laid  bare 
over  a  large  area  through  the  destruction  of  the  overlying  soft  paits. 
:  Toxic  gangrene  occurs  chiefly  in  ergot  poisoning  as  a  result  of  the 
routraction  of  the  small  vessels  and  formation  of  thrombi.  The  tips  of 
ihe  extremities  are  usually  affected. 

\  Infectious  gangrene  occurs  particularly  in  different  infections  of  the 
■;kiu  and  subcutaneous  tissue,  and  may  be  associated  with  gas-formation. 
In  the  form  known  as  foudroyaiit  gangrene  different  varieties  of  bacteria 
jiave  been  found;  the  bacillus  of  malignant  oedema,  an  anaerobic  bacil- 
lus (Welch,  E.  Frankel,  Hitschmann  and  Lindenthal),  proteus  (Ilauser), 
;uid  bacterium  coli.  Infections  associated  with  ])utrid  gangi-ene  may 
jccur  in  the  internal  organs,  but  affect  chiefly  the  lungs  and  intestines. 
j  A  so-called  neuropathic  gangrene  occurs  when  a  tissue  affected  with 
•ither  sensory  or  motor  paralysis  is  M^ounded  or  subjected  to  continued 
i)ressure.  It  is  dependent  partly  upon  circulatory  disturbances  and 
tartly  upon  infection.  Gangrene  resulting  from  the  Avit-hdrawal  of  the 
ntlueucv^  of  trophic  nerves  has  not  yet  been  demonstrafed.  Symmet- 
ical  gangrene,  which  affects  corresponding  parts  of  the  extremities 
;nd  has  l)een  regarded  by  many  as  a  neuropathic  disease,  is  de])eiident 
';ipon  clianges  in  the  blood-vessels;  likewise,  the  perforating  ulcer  of  the 
loot  {nml  perforant  dii  pied),  which  begins  as  a  callosity  following  me- 
jhanical  influences,  and  is  characterized  by  an  accomptinying  gangrene 
I'hich  rapidly  penetrates  into  the  deeper  tissues,  is  dependent  ujxtn  the 
[losure  of  an  artery  of  the  foot. 

I  In  moist  gangrene  the  tissues  break  down  with  a  Aarying  degree  of 
bpidity,  the  fascite  resisting  for  the  longest  time.  As  crystallin*'  prod- 
jets  of  the  chemical  changes  there  may  be  found  needles  of  fat  and 
i^TOsin,  spherules  of  leucin,  coffin-lid  crystals  of  ti-iple  phosjjhate,  and 
Irystals  of  hsbmatoidin.  If  the  gangrene  comes  to  a  standstill,  the  gan- 
reiious  tissue  becomes  sequestrated  through  the  formation  of  a  zone 
If  demarcation — that  is,  becomes  separated  fi-om  the  living  tissue,  and 
nder  favorable  conditions  maybe  thiown  off  from  the  body.  In  the 
!ise  of  necrotic  portions  of  bone  a  very  long  tim(;  is  re(|uii'ed  for  secjues- 
fiition.  Extension  of  gangrene  (through  infection  or  cont inned  circu- 
tory  disturbance)  leads  sooner  or  later  to  death,  especially  if  tuxicsub- 
ances  or  bacteria  are  taken  up  into  the  blood  or  lymph. 

Literature. 

(Xeerosi.s  and  Gangrene.) 

Ibrecht:  Pathol,  d.  Zelle.     Ergobn.  v.  Lubarsch,  vii..  1902. 

rnheim:   ('oagulationsnekrose  d.  Kern.sch\vund.     Vircli.  Arcli.,  120  lid.,  IMtO. 


180  THE    RETROGRADE    CHANGES. 

Balser:    Ueber  Fettnekrose.     Virch.  Arch.,  90  BcL,  1882. 

Chiari:  I^eber  die  sog.  Fettnekrose.     Prager  med.  Woch.,  1893.  Illll 

Condorelli:  Istio-patologia  del  nucleo  nelle  contusioni,  Catania,  1891.  »   III 

Dejerine  et  Leloir:   Alter,  nerv.  dans  cert,  cas  de  gangrene.     Arch,  de  phys.,  1881. 

Dietrich:   Veriin.  asept.  aufbewahrter  Organe.    Verb.  d.  D.  path.  Ges.,  vi.,  1904. 

Ellis:   (X-Ray  Necrosis)  Lit.     Amer.  Jour,  of  Med.  Sc,  1903. 

Falta:  Gangraena  senilis.     Zeitschr.  f.  Heilk.,  xx.,  1899.  '    M 

Flexner:    Fat  necrosis.      Jour,  of  Exp.  Med.,  1897;   Focal  Necrosis.     Johns  Hopkins    ij   li 

Ilosp.  Rep.,  1897. 
FranQois:   Essai  sur  les  gangrenes  spontanees,  Paris,  1832. 

Frankel:  Ueber  die  Gasphlegmone,  Hamburg,  1893;  and  Miinch.  med.  Woch.,  1899. 
Goldschniidt:  Gangrene symetrique  (endarteriteobliterante).  Revuedemed.,  vii.,  1887. 
Goldmarm:  \'eranderungen    aseptisch    auflaevvahrter    Gewebsstlicke        Fortschr.  d. 

Meil.,  vi.,  1888;    Reiskorperchenhaltiges  Hygrom  der  Sehnenscheiden.     Beitr.  v. 

Ziegler,  vii.,  1890. 
Haga:  Spontane  Gangran.     Virch.  Arch.,  152  Bd.,  1898. 
Hauser :  Vork.  v.  Mikroorg.  in  leb.  Geweben.     A.  f.  exp.  Path.,  xx.,  1886. 
Hitschmannu. Iiindenthal: Gangrene foudroyante.    Sitzb. d.  Ak. d.  Wiss., Wien,  1899. 
Hochenegg:  Ueber  symmetrische  Gangran  u.  locale  Asphyxie,  Wien,  1886. 
Israel:  Aniim.  Nekrose  d.  Nierenepithelien.     Virch.  Arch.,  123   Bd.,  1891;     Biolog. 

Studien,  ib.,  141  Bd.,  1895;  147  Bd.,  1897;  Tod  d.  Zelle.     Berl.  klin.  Woch.,  1897. 
Jacoby:  Bedeutung  d.  Fermente  f.  d.  Pathologic.     Cbl.  f.  a.  P.,  xvi.,  1902;    Wirkung 

d.  intra cellularen  Fermente.    Beitr.  z.  chem.  Phys.,  iii.,  1903. 
Kaufmann:  Die  Sublimatintoxication,  Breslau,  1888.     Virch.  Arch.,  117  Bd.,  1889. 
Kraus :  Im  abgestorb.  Gewebe  auftretende  Veranderungen.       Arch,  f .  exp.  Path.,  xxii., 

1886. 
Langerhans:  Ueber  multiple  Fettgewebsnekrose.     Virch.  Arch.,  122  Bd.,  1891. 
Le  Count:  Focal  Necrosis.     Jour,  of  Exp.  Med.,  1897. 
Lesser:  Anat.  Veranderungen  d.  Verdauungskanales  durch  Aetzgifte.     Virch.  Arch./ 

s;!  Bd.,  1880. 
Iiegros:  Rech.  hist,  sur  les  gangrenes  gazeuses.     A.  de  med.  exp.,  1903. 
Levai:  Mai  perforant  du  pied.     Zeit.  f.  Chir.,  49  Bd.,  1899. 
Mallory:  Focal  Necrosis.     Jour,  of  Exp.  Med.,  1898;    Necroses  of  the  Liver.     Jour. 

of  .Med.  Research,  1901.  '■ 

Miiller:  Obor  die  Bedeutung  der  Selbstverdauung.  XX.  Kongr.  f.  inn.  Med.,  1902.  j 
Neuberger:  AA'irkung  dcs  Sublimates  auf  die  Nieren.  Beitr.  v.  Ziegler,  vi.,  1889.  , 
Obolonsky  u.  Ziegler:  Wirkung  d.  Phosphors  auf  Leber  u.  Nieren.     Beitr.  v.  Ziegler,) 

ii..  1887.  _  ! 

Obernddrfer:  Koagulationsnekrose  d. Muskelfaser.   B.v.   Ziegler,  xxxi.,  1902.  j 

Peiper:   I^iterige  Schmelzung  der  Gewebe.     Virch.  Arch.,  118  Bd.,  1889.  i 

Pfitzner:  Zur  pathologischen  Anatomic  des  Zellkerns.  Virch.  Arch.,  103  Bd.,  1886. 
Rath:  Bakteriologie  der  Gangran.     Cbl.  f.  Bakt.,  xxv.,  1899.  ! 

Raynaud:  Ue  I'asphyxie  locale  etde  la  gangrene  symetrique  des  extremites,  Paris,  1862. : 
Reed:  Focal  Necrosis.     Amer.  Jour,  of  Med.  Sc,  1895.  ' 

Rischpler :  Histol.  Veranderungen  nach  der  Erfrierung.     Beitr.  v.  Ziegler,  xxviii.  1900. ' 
Salkowski:  Ue))er  Autolyse.     Deutsche  Klinik,  xi.,  Berlin,  1903  (Lit.). 
Schmaus:  Zclltod.     Ergebn.  d.  allg.  Path.,  iii.,  Wiesbaden,  1897. 
Schmaus  u.  Albrecht:  Ueber  Karyorrhexis.     Virch.  Arch.,  138  Bd.,  1895  (Lit.);  Die 

kiisige  Nekrose,  lb.,  144  Bd.,  Supplh.,  1890;    Coagulationsnekrose.     Deut.  med.! 
_  Woch.,  1899. 
Seitz:  Blutung,  Entzundung  u.  brandiges  Absterben  des  Pankreas,  Berlin,  1892. 
Sternberg:  I'hidartoritis  u.  spontane  Gangran.     Virch.  Arch.,  161  Bd.,  1900. 
Tesdorpf:   Synunctri.sclie  Gangran.     Arch.  f.  Psych.,  33  Bd.,  1900. 
Tomasczewski:  Malum  perforans  pedis.    Miinch.  med.  Woch.,  1902. 
Verworn:  .\llg.  Piiysiologie,  Jena,  1897;  DerkornigeZerfall.  Pfliig.  Arch., 63 Bd.,  1896.' 
von  Wartburg:  Spontane  Gangran.    B.  v.  Bruns,  35  Bd.;  Das  Mai  perforant.    Ibid. 

••;(i  Bd.,  1902  (Lit.). 
Weigert:  Pathologische  Gerinnungsvorgange.     Virch.  Arch.,  79   Bd.;   Coagulations 

nckro.sc  mit  besonderer  Beriicksichtigung  der  Hyalinbildung  und  der  Umpraguiifi 

geronnencr  Massen.     Deut.  med.  Woch.,  1885;  W'eisse  Thromben.     Fortschr.  d 
Med.,  v.,  1887;  Coagulationsnekrose  oderlnspissation.     Cbl.  f.  allg.  Path  . 
Weiss:  Venenspasmus.     Wien.  med.  Presse,  1882;   Symmetr.  Gangran.     Wien.  niediii|!;  r 

Klin..  1882.  >  '      :>  ^  i^U^, 

Wells:  i:.\perimental  Fat  Necrosis.     Jour,  of  Med.  Research,  1903.  'W^^ 

IV.   Hypoplasia,  Agenesia,  and  Atrophy. 
§  51.   Hypoplasia,  or  the  defective  development  of  anlage,  may  affeCj^^^^  ^ 


HYPOPLASIA. 


181 


'ither  the  body  as  a  wliolo  or  only  siiij;le  orjxaiis  or  parts  of  organs,  and 
nay  occur  either  during  the  period  of  intra-uterine  development  or  hiter 
luring  the  period  of  post-embryonal  developmeut. 

"When  either  the  entire  skeleton  or  at  least  the  greater  part  of  it  is 
inder-develoi)ed,  and  especially  if  the  bones  do  not  attain  their  normal 
eugth,  tlie  alfected  individual  is  abnormally  low  in  statnre,  and  is  called 
I  </«•«// (Figs.  43  and  44).  The  individual  parts  may  be  faii'ly  Avell  ])i-o- 
jortioned  (Fig.    43),  or  they  may  be  uusymmetrically  developed  (Fig. 


Fk;.  43. 


Fic.  44. 


;  Fig.  43.— Skeleton  of  a  female  oretin,  thirty-one  years  of  age.  118  cm.  m  heiprlit,  with  klinocephalic 
Sill.  The  cartilage  sutures  of  the  diaphyses  of  the  long  bones  and  pelvic  bones  still  show  ;  as  doe«  also  the 
Intal  suture.  The  individual  parts  of  the  skeleton  are,  on  the  whole,  in  the  proper  proportion,  ihe  upper 
treinities  alone  being  relatively  short. 

'  Fig.  44.— Skeleton  of  a  female  dwarf  of  flfty-eight  years  of  age,  117  cm.  in  height,  with  very  short 
f.remities,  and  long  trunk.    The  cartilage  sutures  are  still  present;  the  articular  ends  of  tho  bones  are 


4).  For  example,  the  trunk  may  be  of  normal  size,  Avliile  tlie  extrem- 
ies  are  abnormally  short  (Fig.  44);  or  both  the  trunk  and  the  extrem- 
ies  may  be  abnormally  small,  Avhile  the  head  is  of  normal  size,  and 
cisequently  appears  relatively  too  large  for  the  small  body.  When  the 
l;'k  of  development  affects  individual  parts  of  the  skeleton  exclusively, 
0  if  it  is  more  marked  in  certain  parts  than  elsewhere,  there  results  a 


182 


THE    KETROGRADE    CHANGES. 


} 


stunting  of  individual  portions  of  the  body.  For  example,  defective  de- 
velopment of  tlie  cianium  gives  i-ise  to  microcephalus  (Fig.  45)  and 
micrencepJialus  (Fig.  4G)  ;  through  defective  development  of  the  humerus 

or  of  the  bones  of  the  hand  there  re-i 
sidts  a  shortening  of  the  upper  arm 
or  of  the  hand ;  and  through  hypo* 
plasia  of  the  lateral  masses  of  th(; 
sacrum  the  transverse  diameter  oJ 
the  pelvis  becomes  diminished. 
^  .v^'i'.'  1^  ^^  *^®  individual  organs  th( 

"  '^^      '  *"■  ''  central  nervous  system  (Figs.  4( 


Fig.  45.  — Ht-ad  of  Helene  Becker  (microcephalic), 
at  age  of  Ave  years.  (From  a  photograph  taken  by 
A.  Ecker,  in  1868.) 


Fig.  46.— lirain  of  Helene  Becker  (micro-  i 
cephalic")  who  died  at  the  age  of  eight  years.  | 
(After  von  Bischoff.)  This  brain  weighed  , 
219  gm.  (instead  of  1,377  gm.,  according  to 

Vierordt). 


and  47),  and  the  genito-urinary  tract  in  particuhir  suffer  very  f requentl ; 
a  stunting  of  development,  although  the  intestines,  heart,  lungs,  liveii 


i 


Fig.  47.— Hypoplasia  and  microguia  of  the  It  ft  ((Kbtal  hemisi)heie,  from  a  deaf-mute,  a,  Ei 
hemisphere;  /),  left  hemisphere;  (,  occipital  lobe  presenting  a  condition  of  microg\ria;  ri,  raembran 
cyst  in  the  region  of  the  paiietal  lobe.  (Seen  from  abo\e,  after  removal  of  the  ceiebellum  Two-th: 
natural  size.) 


HYPOPLASIA  :    A(;h.\ksi  A, 


is;{ 


etc.,  do  not  escape  similar  disturbances  of  jjrowth.  For  example,  the 
entire  brain  (Fiji'.  46),  or  only  one  of  the  heniisi)heres,  or  a  ])art  of  the 
latter  (Fii;-.  47,  (\  </)  may  fail  of  comi)k'te  development.     Tlic  intestine 


Fig.  48.— Hypoplasia  of  the  uterus  with  well-developed  ovaries,  but  wittiout  ripe  follicles.    From  a  cretin, 
twenty-eight  years  of  age. 


may  in  part  be  represented  by  a  tliin  canal  incapable  of  fnnctionating 
(Fig.  49,  d),  or  even  by  a  solid  cord  (Fig.  40,  e).  The  nterns  not  infre- 
quently remains  in  an  undeveloped  state  (infantile)  (Fig.  4.S),  and  occa- 
I  sioually  at  the  time  of  puberty  the  ovary  (Fig.  50,  e),  or  the  entire  inter- 
1  nal  generative  apparatus,  and  at  times  also  the  external  oi-gans  may 
I  remain  in  the  undeveloped  state  of  the  young  child.  A  more  or  less 
1  marked  hypoplasia  of  the  kid- 
■  ney  is  not  rare.  In  the  de- 
'  velopment  of  the  respiratory 
'  tract  the  alveoli  of  a  portion  of 
I  the  lung  may  wholly  fail  to  de- 
i  velop. 

The  above  -  mentioned  ex- 
I  amples  of  hypoplasia,  to  which 
I  many  others  might  be  added, 
I  arise  partly   through  intrinsic 
'  causes   inherent  in  the   germ, 
and  are  therefore  inheritable, 
,  and  partly  through  the  action 
i  of    extrinsie   injurious    intlu- 
ences  upon  normal  anlage  dur- 
ing the  course  of  development. 
I  For  example,  the  growth  of  the 
1  bones  may  be  intluenced   and 
;  retai'ded  by  imjjerfect  function 

I  of  the  thyroid  gland  or  disuse,  and  inllammatiou.  Total  failure  of  por- 
tions of  the  body  or  of  single  oigans  to  deveh)p  is  known  us  agenesia. 
I  This  condition  is  dependent  either  upon  the  non-formation  of  the  anlage, 
I  or  upon  the  destruction  of  the  latter  after  they  have  begun  to  «U'veh>|». 
I  (See  chapter  on  Malformations.) 


Fii;.  49.-  llyiH,],!; 
new-b(irn  rliild.  n 
p<jrti()ii  slmwiri!.'  ii 
normally  (Icvcldpi-il 
size.) 


all  inli'Stiui 

of   the 

i:  and  stmil 

V.'->rVc|llllS 

Ilk' :  .''. 
latiira 

184  THE    RETROGRADE    CHANGES. 

The  tissue  composing  hypoplastic  organs  or  parts  of  organs,  though 
of  less  bulk  than  normal,  may  present  no  abnormalities  of  structure.  In 
other  cases  there  may  be  associated  with  the  smallness  of  size  a  disturb- 
ance of  internal  organization,  so  that  often  the  more  highly  specialized 
elements  of  the  organ  fail  of  development,  the  hyimplasia  being  at  the  same 
time  associated  with  an  agenesia  of  individual  parts.  Thus,  for  example,  in 
hypoplasia  of  the  ovary  (Fig.  50,  e)  the  development  of  the  ova  and  thej 
ripening  of  the  follicles  may  fail  in  part;  in  hypoplasia  of  the  brain 
there  may  occur  at  the  same  time  a  defective  development  of  the  gan- 


FiG.  50.— Cross  sections  of  ovaries  at  different  periods  of  life.  (Hsematoxylin  and  eosin.)  a,  b,  c,  d, 
Normal  ovaries ;  a,  girl  of  Ave  years ;  h.  twenty-three  years ;  c,  twenty-nine  years  ;  and  d.  twenty-one| 
years;  e,  hypoplastic  ovary  of  girl  of  twenty-seven  years  ;  /,  g,  senne  ovaries  from  women  of  eighty  and, 
eighty-three  years  of  age.     (Natural  size.)  ' 

glion-cells  and  nerve-fibres,  and  at  times  portions  of  the  brain  may  cou^j 
sist  only  of  membranous  masses  (Fig.  47,  d)  in  which  no  ganglion -cells' 
are  present.  In  hypoplasia  of  the  lung  there  may  be  under  certain  con-l 
ditions  a  complete  failure  of  development  of  the  alveoli,  so  that  the! 
lung-tissue  consists  merely  of  a  very  vascular  connective  tissue  through-; 
out  which  lie  the  bronchi,  the  latter  in  the  course  of  time  iTSually  be-; 
coming  dilated. 

Literature. 

{Hypoplasia  and  Agenesia.) 

Forster :  Die  Missbildungen  des  Menschen,  Jena,  1865. 

Hertz:  Uebcr  Hemiatrophia  facialis  progressiva.     Arch.  f.  Kinderheil.,  vii.,  1887. 
Hektoen :  Anatomical  Study  of  a  Short-limbed  Dwarf.     Amer.  Jour,  of  Med.  Sc,  1903 . 
Mehnert:  Die  individuelle  Variation  d.  Embryo.     Morph.  Arb.  v.  Schwalbe,  v.,  1896' 
Paltauf,  A. :  Ueber  den  Zwergwuchs,  Wien,  1891. 
Rahlmann:  :\Iikr(i])litliulinus  u.  Hcmimikrosoma,  Stuttgart,  1897. 
Vierordt:  Anutomische,  physiologische  u.  physikalische  Daten  u.  Tabellen,  Jena,  1888 
See  also  Chapter  IX. 

§  52.  Atrophy  is  a  diminution  in  the  size  of  an  organ  due  either  to  J 
diminution  in  size  or  disappearance  of  its  individual  elements.  It  maj' 
occur  at  any  jjeriod  of  life,  and  is  a  very  common  result  of  many  path' 
ological  i)rocesses.  Within  certain  limits  it  may  be  regarded  as  aphysii 
ological  phenomenon,  in  that  in  old  age  there  constantly  occurs  a  certaiii 
degree  of  retrograde  change  in  all  the  organs,  associated  with  a  diminu: 
tion  ill  their  size.  Certain  organs  undergo  such  an  atrophy  with  partia 
<jr  total  loss  of  their  functional  power,  even  before  old  age,  as,  for  exami 
l)h',  the  thymus,  Mhich  atrophies  completely  even  before  the  end  of  th<; 
period  of  growth ;  and  the  ovary  (Fig.  50,  /,  g),  a  part  of  whose  ova  ar! 
discharged  during  the  period  of  sexual  activity,  the  remainder  beinii 


ATKOPHY. 


ISf) 


destroyed.  In  old  age  the  lymphadenoid  tissues,  the  muscles  aiul  bones, 
iu  particular,  surt'or  atrophy,  thouj^h  the  tissue-changes  of  senility  vary 
greatly  in  ditferent  individuals,  so  that  often  other  (issues,  Ihc  glandular 
organs  or  the  brain,  show  the  most  marked  atrophy. 

The  atrophy  of  an  organ  is  characterized  chielly  by  its  dimimition  in 
size.  In  atrophic  conditions  of  the  muscles  (Fig.  51)  the  alfected  ])or- 
tions  of  the  body  become  smaller,  and  in  extreme  cases  the  extr«'mities 
appear  as  if  consisting  only  of  skin  and  bones.  When  the  ati;>i)hy  of  an 
organ  is  uniform  throughout,  its  normal  shape  may  be  preserNcd;  but  if 
the  atrophy  progresses  more  rapidly  in  certain  i>arts  than  in  olheis,  the 
surface  of  the  organ  may  show  local  de- 
pressions (Fig.  53)  and  cicatricial  con- 
tractions (Fig.  50),  so  that  the  organ,  for 
example,  the  liver  or  kidney,  may  present 
a  knobbed  or  granular  appearance.  When 
tissues  which  are  undergoing  atrophy  ar<' 
prevented  from  contracting,  as  in  the  case 
of  the  bones  and  lungs,  the  external  form 
is  preserved.  In  the  case  of  bone,  the 
medullary  spaces  and  the  Haversian  canals 
l3eeome  enlarged,  and  a  condition  results 
which  is  known  as  excentric  atrophy  or 
osteoporosis  (Fig.  52).  In  the  lungs  the 
alveoli  become  confluent  into  large  air- 
spaces as  the  result  of  the  disapj)earance 
of  the  intervening  walls. 

In  atroi^hy  of  the  glands  and  muscles 
there  occurs  frequently  a  change  of  color, 
though  this  is  of  secondary  importance. 
Either  the  normal  pigmentation  of  the 
:  affected  organ  is  brought  out  more  dis- 
tincthi  by  its  atrophy,  or  associated  with 
the  atrophy  there  is  a  deposit  of  pigme^d 
{hroicn  ov  pigment  atrophy),  or  finally  the 
change  of  color  may  be  dependent  upon 
the  changed  blood-content  of  the  atrophic 
!  tissue. 

j  The  diminution  in  size  of  atrophic  organs 
\is  the  result  of  a  diminution  in  size  and  dis- 
appearance of  the  histological  elements  com- 
\  posing  them.  In  the  majority  of  the  or- 
gans, i»articularly  in  the  glands,  muscles, 
and  bones,  the  specific  cells  which  perform 
[the  especial  function  of  the  affected  or- 
igan, are  affected  in  atrophy  to  a  far 
Igreater  degree  than  the  supporting  connective-tissue  framework.  Indeed, 
jit  may  be  frequently  observed  that  the  connective-tissue  elements  may 
ibe  wholly  preserved,  or  even  increased  in  numbei-,  while  th<^  moie  high- 
ily  specialized  elements  have  disappeared.  Thus,  for  example,  in 
atrophic  muscle  fFig.  54)  the  contractile  substance  within  the  saico- 
lemma  (a)  may  disappear  to  a  very  great  extent  (h)  without  the  occur- 
rence of  any  atrophy  whatever  of  the  connective  tissue  lietween  the 
nauscle-bundles.  The  nuclei  (cj  of  the  connective  tissue  may  even  be 
increased  iu  number. 


Juvenile  iniisciiliir  alropliy. 
observed  by  tie  Souzii.) 


186 


THE    RETROGRADE    CHANGES. 


lu  atrophy  of  the  kidney  the  epithelial  cells  of  the  urinary  tubules 
(Fig.  55,  (i)  ixM'onie  smaller  (/)  and  may  tiually  wholly  vanish  so  that 
the  tubules  collai)se.  Likewise,  the  epithelium  of  the  glomeruli  {d)  is 
lost,  while  the  capillaries  become  obliterated. 

The  same  thing  occurs  in  simple  atrophy  of  the  liver,  in  that  all  the 
liver  cells  of  a  lobule  may  disappear  without  any  perceptible  decrease  of! 
the  supp;)rting  reticulum.  Likewise  the  ganglion  cells  of  the  brain  and! 
spinal  cord  may  atrophy  without  the  neuroglia  being  diminished.  Not 
infrequently  the  latter  may  become  increased. 

In  ati-ophy  of  the  bones  the  true  bone-tissue  becomes  diminished.  In 
atroi)hy  of  the  bone-marrow  the  total  mass  of  free  marrow-cells  is 
diminished.  The  supporting  cells  may  in  consequence  take  up  an  in- 
creased amount  of  fat;  but,  on  the  other  hand,  the  fat  in  the  cells  of  the 

marrow  may  also  vanish,  sO' 
that  free  spaces  which  be-i 
come  filled  with  fluid  arei 
formed  between  the  support-' 
ing  cells. 

In  atrophy  of  the  lymj^h 
glands  and  of  the  spleen  th( 
free  cells  in  i^articular  disl 
appear  and  in  parts  are  com 
pletely  absent. 

The  changes  leading  t( 
atrophy  may  take  place  with 
out  the  occurrence  of  any 
apparent  change  of  structun 
in  the  individual  tissue-ele. 
ments  (Fig.  54),  so  that  th(! 
condition  of  atrophy  iij 
reached  essentially  through 
a  loss  of  volume  of  the  in| 
dividual  parts.  Both  th<^ 
cell -body  and  the  nucleui. 
nmy  become  smaller;  an(| 
the  latter  change  may  be  oh^ 
served  particularly  in  thij 
liver  in  cases  of  starvationl 
atrophy  (Lukjanow).  Thi| 
form  of  atrophy  is  kuowi 
as  simple  atrophy,  and  i 
to  be  distinguished  from  tb 
degenerative  atrophies,  ii 
w  h  i  c  h  the  tmue-elemenU 
daring  the  progress  of  thf 
(dropluj  shoio  changes  in  thei'\ 
structure,  and  frequentllj 
contain  ])athological  substances.  Thus  a  cell  may  become  granular] 
and  undergo  fragmentation,  or  may  swell  up  and  liquefy,  or  ther 
maybe  formed  within  the  cell  drops  of  fat  or  mucus;  all  of  thes 
chajiges  signifying  degenerative  conditions  of  the  cell -protoplasm 
These  processes  aie  classed  as  special  forms  of  degeneration  and  will  b 
discussed  in  the  paragraphs  of  the  following  section.  Degenerativ 
ehanges  can  occur  at  the  same  time  in  the  nuclei,  as  shown  by  fragmeu 
♦ation,  distorted  snape,   clumping  of  the  chromatin,  diffusion  of  chrc 


-Exfentric  atrophy  of  tlie  lower  end  of  the  tibia  and 
llbula,  with  osteoporosis.     (Natural  size.) 


I 


ATKOIMI  V 


1S< 


imitiii  into  the  eoll-protoi)l:isin,  swollinu-  and  li(iii(>f:u-i  ion  of  ilit>  luiclcus. 
All  these  processes  lead  ultimately  to  the  disappearance  of  the  micleus 
and  the  destruction  of  the  cell. 

The  dejieue  rat  ions  leadiiij;-  ultimately  to  a  condition  of  atrophy  of  the 
affected  or^an  ai"e  of  verv  fre([n('iit  occurrence,  ]»art ic',ilarl\-  in  .ulaiKhilar 


Fig.  53.— Senile  atrophy  of  the  skull-eap,  with  defect  of  the  exteruul  table  and   the  spongy  portion 
throughout  the  central  portion  of  both  parietal  bones. 

organs.     The  process  is  often  complicated  by  the  occurrence  of  inflain- 
matiou. 

According  to  their  genesis  the  forms  of  atrophy  may  be  classed  as 
active  or  passive.  In  the  former  the  cell  is  no  longer  able  to  make  use 
of  the  food  brought  to  it;  in  the  latter  the  food  is  either  not  supplied  to 
the  cell  in  sufficient  cpiantity  or  in  the  proper  form,  or  harmful  sub- 
stances are  brought  to  the  cells  which  impair  their  function.     Active 


Fig.  54.— Sei  tion  of  an  aliophH    imunc  It     fr   in    i 
fluid,  Bismarck  brow  n  )    a.  Normal  iims<  i<  nines     /<    iii 
nuclei  of  which,  at  Ci,  seem  to  be  increased  in  munht  i 


0 

,    .1      M         inilMUlir 

1-  li  111  H  -..  (    pt  ruinx 

rn.phy.     (MiiMcr's 
nun  interuuin,  Iho 

atrophy  is  particularly  a  pai-t  of  sfuiJe  def/enrration  (see  above),  but  it 
occurs  also  under  pathological  conditions,  especially  in  the  case  of  nerves, 
glands,  and  muscles  (Fig.  51)  wliose  functional  activity  is  not  called  into 
play. 

The  clinician    ordinarily  prefei'S   anoth<'r  classihcation  of   atrophy; 


188 


THE  ri:trograde  changes. 


namely,   senile   atrophy,  atrophy  due  to  impaired  nutrition,  pressure 
atrophy,  atrophy  of  disuse,  and  nenroijathic  atrophy. 

Senile  atrophy  (Fig.  53)  is  partly  active,  and  partly  passive,  in  that 
it  is  not  simply  the  result  of  the  diminishing  vital  energy  of  the  cell,  but 

also  depends  in  part  upon 
the  narrowing  and  obliteration 
of  the  vessels  conveying  nour- 
ishment to  the  cells.  It  may 
occur  in  all  the  organs,  but  is 
often  more  marked  in  one 
organ  than  in  another.  The 
bones,  kidneys,  liver,  brain, 
and  heart  may  undergo  a 
marked  loss  of  volume. 

Atrophy  due  to  impaired 
nutrition  may  result  in  the 
first  place  from  an  insufficient 
supply  of  food  to  the  body  as 
a  whole,  or  from  extensive 
loss  of  the  fluids  of  the  body. 
In  these  cases  the  whole  body 
is  affected,  though  the  fat, 
blood,  muscles,  and  the  ab- 
dominal organs  suffer  to  a 
greater  extent  than  the  re- 
maining tissues.  Local  atrophies  may  result  from  local  disturbances  of 
circulation,  and  are  the  frequent  sequelae  of  diseases  of  the  arteries  in  which 
the  vessel  lumen  is  narrowed  (Fig.  56).  Further,  they  are  of  frequent 
occurrence  as  a  result  or  a  i)art  of  inflammatory  processes ;  but  it  should 
be  noted  that  in  these  cases  the  condition  is  not  of  the  nature  of  a  simple 
atrophy,  but  rather  of  various  degenerative  changes  leading  to  the  death  of 
the  cells  and  of  the  tissues. 

At  times  atrophy  results  from  the  presence  of  deleterious  substances 
in  the  blood.     For  example,  iodine  causes  a  diminution  in  the  size  of  the 


Fig.  55.— Senile  atrophy  of  the  kidney.  (Alcohol,  alum- 
carmine.)  a,  Normal  urinary  tubules;  b,  normal  glomeru- 
lus ;  c,  stroma  with  blood-vessels ;  d,  atrophic  and  obliter- 
ated grlomerulus  ;  e,  small  artery,  with  thickened  intima  ;/, 
atrophic  and  collapsed  urinary  tubules.    X  200. 


^^^k^ 


Fig.  50.— Arteriosclerotic  atrophy  of  the  kidney.     (Natural  size.) 

thyroid  gland.     In  chronic  lead-poisoning  the  extensor  muscles  of  the 
forcjinii  in  ])ai'licnlar  become  atrophic. 

Pressure-atrophy  occurs  when  a  tissue  is  subjected  for  a  length  of 
time  to  a  moderate  pressure  (Fig.  57).  It  depends  partly  upon  direct: 
injury  to  the  tissues  and  partly  upon  disturbance  of  the  circulation.' 
The  most  typical  examples  are :  the  atrophy  of  the  liver  caused  by  thei 


ATHOIMIY. 


ISO 


pressure  of  the  edge  of  the  ribs  upon  the  orfjan  due  to  ti.ulit -hieing  (''cor 
set-liver"),  aud  the  disappearanee  of  bone  (Fig.  57)  following  the  press 
nre  of  an  aortic  aneurism,  tumors,  or  of 
an  aeeumulation  of  fluid  in  the  ventricles 
of  the  brain. 

Atrophy  of  disuse  occurs  in  the  mus- 
cles, glands,  bones,  skin,  and  other  tissncs, 
aud  is  dependent  upon  the  disuse  of  the 
organ  in  question.  In  the  case  of  inusclcs 
and  glands  the  atrophy  is  essentially 
active;  the  nutritive  processes  diminish- 
ing as  the  result  of  the  lessened  func- 
tional activity.  In  the  other  tissues  the 
atrophy  is  essentially  de]>endent  upon 
the  lowering  of  nutrition  of  the  disused 
parts,  though  a  change  in  the  power  of 
assimilation  of  the  cells  cannot  be  wholly 
excluded.  AVhen  the  inactivity  occurs 
during  the  jieriod  of  development,  and 
the  tissue  as  a  result  becomes  stunted,  the 
condition  is  to  be  regarded  as  a  hypo- 
plasia, though  no  sharp  line  can  be  drawn 
between  hypoplasia  and  atrophy,  since  in 
the  former  there  may  be  also  a  disappear- 
ance of  structures  which  had  undergone  a 
certain  degree  of  development. 

Neuropathic  atrophy  is  a  result  of 
diseased  conditions  of  the  nervous  system, 
and  is  apparent  most  often  in  an  atrophy 
of  the  nerves  and  muscles,  though  other 
tissues  jnay  be  affected. 

For  example,  after  destruction 
of  the  anterior  horns  or  of  themolor 
roots  of  the  si)inal  cord,  there  fol- 
lows an  atrophy  of  the  correspond- 
ing nerves  and  muscles.  After  in- 
jury of  the  peiii)heral  nerves  the 
skin  often  becomes  atrophic.  Ac- 
cording to  many  authors,  disease  of 
the  nerve-trunks  of  one  side  of  the 
face  is  followed  ])y  n  iniihitmi}  iini 
ropotliic  facial  atrojtin/  (Vlis;.  ."iS),  but 
by  otlieis  (^Mobius)  the  neuropathic 
nature  of  this  condition  is  contest«'d. 
Unilat<'ral  affections  of  the  brain  in 
foetal  life  or  during  childhood  may 
lead  to  atrophy  of  tlie  ojjposile  side 
i»f  the  bodv  (congenital  and  infantile 

-Facial  hemUtUophy.     (After  Lichtbeiu.       /,,.,„latrophy). 


COltlll 

Isiu. 


atrophy  of   the  spiniil 
due  to  pressure   l)y  aortic  aucur- 


190  THE    RETROGRADE    CHAXGES. 


Literature. 

(Atroj^hy.) 

Borel-    Contributiou  a  1' etude  des  asymetries  du  visage.     These  de  Berne,  Geneve, 

ISSo. 
Charcot :  Maladies  des  vieillards.     CEuvres  compl.,  vn. 
Coen:    Suir  iuanizione  acuta.     Bull,  delle  Scienze  Med.  di  Bologna,  ser.  vii.,  vol.  i., 

1N90. 
Demange:  :&tude  cliuique  et  anatomo-pathologique  sur  la  vieillesse,  Paris,  1B86 
Demme:   Hemiatrophia  facialis,     xxii.  Ber.  ilb.  d.  Thatigkeit  d.  Kinderspitals,  Bern, 

Flamming- •  Riclitunffsfigur  im  Ei  bei  Untergang  d.  Follikel.     Arch.  f.  Anat.,  1885. 
Hammelshein  u.  Leber:   Atrophic  d.    Netzhaut  nach  Endarteriitis.  A.  f.  O.,   Ui., 

lUOO. 
Herz:  Hemiatroph.  fac.  progressiva.     Arch.  f.  Kinderheilk.,  viii.,  1887. 
Homen:    Zur  Kenntniss  der  Hemiatrophia  facialis.     Neurol.   Cbl.,   1890;    Festskrift 

fran  Pathologisk-Anatomiska  Institutet,  Helsingfors,  1890. 
Jarotzky:  YerSud.  d.  Pankreaszellen  bei  Inanition.     Virch.  Arch.,  156  Bd.,  1899. 
Joseph.:   Trophische  Nerven  (Haarausfall  nach  Nervenexcision).     Yirch.  Arch.,  107 

Bd.,  1887. 
Levin:    Halbseitige  Gesichtsatrophie  (Zusammenstellung  der  publ.  Falle).     Charite- 

Annalen,  ix. 
Lukjanow:  L'inanition  du  noyau  cellulaire.     Rev.  scientif.  Paris,  1897. 
Merkel:  Die  GeAvebe  beim  Alteru.     Verh.  d.  X.  iuternat.  med.  Congr.,  ii.,  Berlin,  1891. 
Morpurgo:    De  la  nature  des  atrophies  par  inanition.     Arch.  ital.  de.  biol.  xii.,  1889; 

Kary(imetri.schc  Untersuchungen  bei  Inanition.     Virch.  Arch.,  152  Bd.,  1898. 
Mobius':  Der  unischriebene  Gesichtsschwund,  Wien.  1895. 

Muhlmann:    Dii-  Veriinderungen  im  Greisenalter.     Cbl.  f.  allg.  Path.,  xi..  1900  (Lit.). 
Notzel-   Klickbikluug  der  Gewebeim  Froschlarvenschwanz.     Arch.  f.  mikr.  Anat.,  45 

Bd.,  1895.  , 

Penzoldt:  Hemiatrophia  facialis.     ]\Iunch.  med.  Woch.,  1886.  | 

Pfitzner  :  Zur  path.  Anat.  d.  Zellkerus.     Yirch.  Arch.,  103  Bd.,  1886. 
V.  Recklinghausen:   Handb.  d.  allg.  Path.  d.  Kreislaufs  u.  d.  Ernahrung,  Stuttgart, 

isii;!. 
Salvioli:  Sulla  pretesa  influenza  trofica  di  nervi.     Arch,  per  le  Sc.  Med.,  1896. 
Seeligmliller :  Gesichtsatrophie.     Eulenburg's  Realencyklop.,  1895. 
Stier:    Yerhaiten  d.  ]\Iusk.  u.  Iserveu  nach  "Liis.  d.  Nervensyst.     Arch.   f.  Psych.,  29 

Bd..  1897  (Lit.). 
See  also  §  51. 

V.  Cloudy  Swelling  and  Hydropic  Degeneration. 

§  .53.  The  term  cloudy  swelling  or  parenchymatous  degeneration  or 
granular  degeneration  is  a])plied  to  that  form  of  cell -degeneration  which  is 
characterized  histologically  by  a  swelling  and  enlargement  of  the  cells 
due  to  the  formation  within  the  cell -protoplasm  of 
free  grannies,  which  according  to  their  microchemi- 
cal  properties  (solubility  in  acetic  acid,  insolubility 
in  alkalies  and  ether)  are  to  be  regarded  as  albumin- 
(  '  '  ^^  ous  bodies.  The  epithelial  cells  of  the  kidney  and 
liver  (Fig.  59),  and  the  cells  of  heart-muscle  frequent- 
no  oa.-(  unicivTweii-  ^y  show  this  degeneration,  therel)y  acquiring  a  cloudy 
inp  uV iivrr-vciis  (srrapinp  appearance,  as  if  covered  with  dust,  while  at  the  same 
the"iiverof 'a  man^dyinff  time  their  normal  structure  (filamentous,  granular, 
i^n  mS"s!iR  soultfc*  alveolar)  and  form  are  lost.  Thus,  for  example,  iu 
xavi.        '  '       cloudy  swelling  of  the  kidney-epithelium  the  rod-like 

markings  of  the  protoplasm  are  lost  (Fig.  60,  a),  as 
are  also  tlie  cell -processes  projecting  into  the  lumen  of  the  tubules. 
The  swollen  cells  (b,  e,  d)  are  larger,  more  plump,  and  contain  dark 
granules.  This  change  is  to  be  regarded  as  a  disorganization  of  the  proto- 
plasm following  an  absorption  of  tluid,  and  leads  to  partial  separation  of 


CLOUDY    SWKLLIXC 


191 


the  solid  and  li(inid  constituoiits    of  the  i)rol()i)l:isiii.      Al  1Iu's;iii 
the  nucleus  swrUs  and  undergoes  disorgauizidioii. 

Recovery  is  j)ossible  at  a  certain  dciiicc,   and  tlu'  cells  may 
stored  to  their  uoriual  condition.     Jn  other  cases  liie  cell  body 


lie  le 
is  de 


-".'.I 


A':-*''' 


^-i^v« 


'  Fio.  6(1.— Cloudy  swelling  of  kidney  epithelium.  (Chromic  acid,  ammonia,  glycerin.)  a.  Normal 
jepithelium  ;  /).  beginning  cloudy  swelling ;  c,  advanced  stage  of  cloudy  swelling :  d,  desquamated  degen- 
lerated  epithelium.     X  6()0. 

stroyed,  breaking  up  into  granidar  fragments.  Fatty  degeneration  very 
often  accompanies  cloudy  swelling. 

1  Cloudy  swelling  uiay  occur  in  the  cells  of  any  of  the  parenchymatous 
jorgans,  as  the  liver,  kidneys,  or  heart,  during  the  course  of  the  majority 
\)f  the  infectious  diseases,  particularly  in  scarlet  fever,  typhoid,  small- 
liox,  erysipelas,  diphtheria,  septicaemia,  etc.  Tlie  affected  organs  i)re- 
i>eut  a  cloudy,  dull-shining,  often  gray  appearance ;  in  marked  cases  tlie 
brgan  may  appear  as  if  cooked,  the  blood-content  is  very  slight,  the  con- 
Bistencv  doughv,  and  the  finer  details  of  structure  are  lost. 


I  It  is  not  improbable  that  aiitolytic  processes  (see  paragrapli  49)  play  a  role  in 
I'arenchymatous  degeneration  (Lr;«(/s<e{ner).  Or^/er  regards  it  as  an  autolysis  acconi- 
jianied  by  an  iuerease  of  tlie  water-content.  Tlie  granules  which  become  visible  and 
how  double  refraction  he  regards  as  protugon,  which,  din-ing  autolysis,  is  eitlier  prc- 
iTved  because  of  its  slight  .solubility  or  during  the  course  of  the  process  is  precipi- 
ited  in  the  form  of  granules. 

Literature. 


((Uoud;/  Sin'/liitf/.) 


I'.tOf. 


.Ibrecht:  Pathol,  d.  Zelle.     Verb.  d.  D.  path.  Ges.,  v.,  190:1.  i 
.mold:  Feinere  Strukturen  der  Leber.     Virch.  Arch.,  IGO  Bd.,  1901. 
enario:  Die  Lehre  von  der  trliben  Schwellung,  "Wur/.burg,  1891. 
aleotti:  Ucber  die  Granulationen  in  den  Zellen.     ]\Iouatssclir.  f.  Anal.,  .\ 
andsteiner:  Ueber  Trubeschwelluug.    B.  v.  Ziegler,  xx.xiii.,  190:i. 
ukjanow:  Grundzuge  einer  ailgein.  Pathologic  der  Zelle,   Leipzig,  1891. 
rgler:  Chemische  Nierenuutcrsuchungen.     Virch.  Arch.,  170  Bil.,   1904. 


l«9r>. 


192 


THE    RETROGRADE    CHANGES. 


Schilling':  Verlialten  der  Altmann'schen  Granula  bei  der  trilben  Scliwellimg.     Virclf 

Arch.,  135  Bd.,  1894. 
Schinaus  u.   Bohm:  Bcfund  iu   der  Leber   bei  Phosphorvergiftung.     Yirch.  Arch)!} 

l.")2  I^d.,  1898.  ] 

Theohari:  Structure  des  cellules  gland.  ^  I'etat  pathol.,  Paris,   1900.  ; 

Verworn:  Der  koruige  Zerfall.     Pfliiger's  Arch.,  63  Bd.,  1896.  ; 

Virchow:  Cellularpathologie.     Arch.,  8.  Bd.,  1855;  Reizuug  u.  Reizbarkeit.    lb.,  1'. 

Bd..  18.J8.  I 

"Waldeyer:  Verilnderungen  der  quergestr.  Muskelfasern.     Virch.  Arch.,  34  Bd.,  186ijj. 
Zenker:   Ueb.  d.  Veranderung  d.  willkiirlichen  Muskeln  bei  Typhus  abdom.,  Leipzig* 


1864. 


§  54.  Hydropic  degeneration  is  that  form  of  degeneration  frequent!, 
observed  in  cells  of  different  kinds,  whereby  they  become  swollen  throng 

the  imbibition  of  flui( 
When  epithelial  cells  nnderg 
this  change  the  cell-conten 
appear  clear,  the  grannies  ( 
the  protoplasm  are  presse 
farther  apart  by  the  liui( 
often  being  crowded  into  | 
ring  at  the  periphery  of  tb 
cell ;  the  cells  thns  coming  1 
resemble  plant-cells  to  a  cei 
tain  extent.  Vacuoles  (Fij 
61^  h) — that  is,  globules  < 
clear  fluid  —  may  often  I 
formed  within  the  cells.  Tl 
nucleus  (c)  also  swells  and  b 
comes  changed  to  a  large  bla<; 
der-like  vacuole  containii; 
clear  fluid.  In  muscles  sho\i 
ing  hydropic  degeneration  clear  droplets  of  fluid  appear  between  tl; 
fibrillse,  pushing  the  latter  apart  (Figs,  62  and  63,  a,  h).  Throu^j 
an  abundant  formation  of  such  drops  the  muscle  fibres  may  acqui , 
in  places  an  appearance  of  foam-like  bubbles  CFig;.  62").  At  firsj 
the  muscle  fibres  between  these  drops  remain  preserved,  but  finally  the; 
undergo  fragmentation  and  lique-  ; 

faction. 

Hydropic  degeneration  of  cells 
may  be  the  result  of  oedema  (Figs. 
62  and  <)3) ;  it  occurs  also  in  inflam- 
matory foci  (Fig.  41,(7)  andintumor- 


*:: 


Fig.  61.— Hydropic  degeneration  of  epithelial  cells  from 
a  carcinoma  of  the  breast.  (Miiller's  fluid,  aniline  brown.) 
a.  Unchanged  epithelium ;  h.  hydropic  cells  containing 
bladder-like  drops  of  fluid  [physalides];  c,  hydropic  nuclei; 
d,  enlarged  nucleoli ;  e,  wandering  cells.    X  300. 


Flfi.  63.— Hydropic  degeiienilion  of  iiins(le-tibre.s 
from  the  calf  muscle  in  chronic  o-dema  of  the  leg. 
(Flemming's  solution,  safranin.)     X  45. 


Fig.  63.— Transverse  section  of  a  muscle] 
bundle  showing  hvdropic  degeneration  of  it; 
fibres.  (Miillcr's  fluid,  hematoxylin.)  a.  Muscle; 
flbtc  with  sihmU  drops  of  fluid;  h,  muscle-flbr<! 

with  hut:.' (hops.     ,-,66. 


cells  (Fi.u'.  61).     In  the  case  of  inflammation  the  degenerative  charaet. 
of  tlic  jnoce.ss  is  more  marked  than  in  the  case  of  oedema ;  anda  coinple 
"iqiicfaclion  of  the  cells  and  nucU'i  may  result.     In  oedema  the  cells, 
spite  of  their  hydropic  condition,  may  remain  alive  for  a  long  time. 


FAT   DEPOSIT    AND    FATTY    1)F(;  K.\  KI{  A'lK 


l!);; 


VI.  Fat  Deposit  and    Fatty  Dejceneraticn. 

§55.  Fat,  in  a  form  that  can  l)e  dcnionstralcd  niicroscoijicallx , 
wiiloly  distiibuti'd  thronghout  the  human  and  animal  (>r,!j,anism.  Jt 
peai's  most  i)rominently  in  tiio  suhcnlancons  and  snhsci'ous  tissues  ; 
the  bone-ma  ri"o\v ;  in  tliese  regions  eharaeterist  ic  adipose  tissue  de\<'l( 
at  a  certain  timedurinj;-  end)iyonal  de\  ('l(»])menl  or  duiiii-;-  ciiildiio 
Less  prominent,  and  in  })art.  visible  only  on  microscopic  examination 
the  fat  present  in  various  inlands,  also  in  siangiion-cells,  cai'tilaj;e-ce 
leucocytes,  surface  epithelium,  duct  epithelium,  endothelium,  etc. 

The  fat  of  adipose  tissue  occurs  in  the  coiuiective-tissue  cells  in  v>h 
it  is  deposited,  in  the  form  of  droplets  that  often  become  confluent, 
that  the  fully  de\"eloped  fat-cell  appears  as  a  fat-spheiule  surrounded 


ap- 
ind 

l)l)S 

od. 


ich 
sc. 
bv 


Fig.  64. — Arliposf  tissue  from  tl 
Siiflan    III.),     a,  Fat  tissue;    b,  luusc 


Ins  of    fill-    hi-iirt.      (■p'ormaliii,  Iia-matoxyliii,  ami 
l1(j  iiitiltratfil  with  fat  tissue.      X  40. 


a  cell-membrane  containin<^  ;i  nucleus.  In  ])r('|tai:it  ions  mounted  in 
Canada  balsam  the  fat -diop  is  represented  by  a  clear  Aacuole  (Fiji;.  <i5, 
'•).  Sudan  III.  and  Scharlach  loth  stain  fat  a  yellowish-red  (Fij^-.  (U  ), 
while  treatment  with  osmic  acid,  whi<;h  is  reduced  by  the  fat,  causes  the 
fat-drops  to  become  blackened  (Fio-.  G7,  c). 

The  fat  contained  in  the  S])ecial  adijiose  tissues  of  the   body    is  a 

stored-up fat  which  th<^  oroanism,  in  case  of  necessity,  may  use  for  its 

preservation,  and  it  may,  therefore,    be  desi-iiiated   as  a,  supply  of  fat 

designed  for  consumption  oi-  temporary  fat.     its  abundance  may  be 

regarded  as  an  indication  of  the  condition  of  iMiti'ilion  ;  when  this  is  jiood 

i  the  adipfise  tissues  are  Avell  de\'eloped,    in   cases  of  star\"ation   and    in 

I  chronic  marasmus  they  may  vanish  entiiely.     There  occurs  an  atrophy 

i  of  fat-tissue,  in  which  the  fat-cells  contain  only  small  droi)lets  of  fat  or 


194 


THE    RETROGRADE    CHAXGES. 


110  fat  at  all,  iu  the  latter  case  revertiug  to  the  type  of  ordinary  couuec- 
tive-tissiie  cells.  The  atrophic  fat-lobules  often  take  on  a  pale  yellow 
color  throuiih  the  formation  of  pigment  iu  the  cells  (ijeUow  atrophy  of 
adipose-tissue).  Through  the  collection  of  fluid  between  the  atrophic  fat- 
cells  the  fat-tissue  (most  frequently  in  the  cardiac  panniculus)  becomeN 
translucent,  resembling  myxomatous  tissue  {serous  atrojyhy  of  adiposr 
tissue). 

Hypertrophy  of  adipose  tissue  leads  to  the  condition  known  a> 
obesity,  adipositas,  or  lipomatosis.  It  is  dependent  primarily  upon 
an  excessive  food-supply ;  but  there  are  frequent  individual  exceptions 
to  this  rule,  since  in  uumy  people  an  increased  formation  of  panniculiiN 
does  not  take  place,  no  matter  how  rich  the  food-supply.  Again,  an 
abundant  deposit  of  tat  occui'sin  some  individuals  when  the  food-supply 


Fig.  65.— Lipomatosis  of  the  calf  muscles,  associated  with  atrophy.  (Miiller's  fluid,  carmine.)  a.  Trans  ,. 
verse  section  of  normal  flbre ;  Oi,  of  atrophic  fibre ;  02,  transverse  section  of  sarcolemma  tube  containing  A 
disintegrated  contractile  substance ;  b,  connective  tissue ;  c,  fat-tissue.    X  60.  ' 

does  not  exceed  the  normal.  In  such  cases  the  cause  of  the  lipomatosis 
must  be  sought  iu  an  inability  on  the  part  of  the  organism  to  destroy  the 
fat  brouglit  to  it  or  arising  normally  within  it. 

In  general  lipomatosis  the  deposit  of  fat  takes  place  iirst  in  the  normalr 
fat-depots,  and  then  later  in  places  that  normally  contain  no  fat,  for  ex- 
ample, in  the  connective  tissue  of  the  muscles,  in  the  myocardium,  and' 
«'ven  beneath  the  endocardium.     A  loeal  lipomatosis  may  occur  in  various; 
regions  of  the  body,  for  example,  in  an  arm,  the  front  of  the  neck,  nape.i. 
etc.,  and  leads  to  defoimities  of  the  affected  regions  resembling  elephau-' 
tiasis.     When  occurring  in  circumscribed  masses  or  nodules  the  cou' 
ditioii  is  classed  with  the  fatty  tumors  known  as  lipomata  (see  Lipoma)., 
A  local  lipomatosis  occurs  also  as  a  x>eculiar  disease  of  the  muscles  ii: 
whicli  withont  the  agency  of  extrinsic  causes  but  as  the  result  of  a  coiii. 
genital  aidage  the  muscles,  particularly  those  of  the  calves  of  the  legs.- 
inci-ease  greatly  in  size  (Fig.  05,  r)  through  the  development  of  adipost 
tissue  in  the  perimysium  internum.      At  the  same  time  they  becoiiK 
weaker,  since  many  of  the  muscle-fibres  (Fig.  65,  a,  a^,  «„)  may  disappea 
{atropliia  musculorum  lipomatosa  pseudohypertropliica).     Finally,  in  othe 


FAT    DKl'OSIT 


19.- 


cases  adipose  tissue  may  develop  secondarily  in  phuvs  wIumc  otlicrlissut 
has  disappeared,  for  example,  within  muscles  (Fi^-  tw;,  r)  that  lune  !•<■ 
come  atrophic  as  the  result  of  disease  of  the  anterior  horn  of  tlic  siiiii;il 


•  Mr^i, 


a. 


Fici.  CO.— Spinal  imi.M'uUir  atmphy  with  hpcini.itiwi's,  m  asoendiiiff  atiopliN  of  the  .inli'tmr is  of  the 

Bfiinal  cord.     (Muller's  fluid,  Bismarck  brown.)     Section  from  tlie  calf  miiscli'.    o,  'I'raiis\ciM'  vfction  nf 
atropine  muscle-Ubres ;  7»,  penm>!«ium;  (,  fat-Kssiie;  d,  artery;  c,  vein.      '  (ii). 

ord  or  in  the  case  of  lymph-glands  tliat  in  old  age  linve  lost,  for  the 

reater  part,  their  lymphocytes. 

The  fat  of  the  glandular  organs  occurs  ordinarily  in  small,  even 
very  minute  droplets,  but  in  the  case  of  a  great  abundaiu'c  of  the  fat 
larger  droplets  may  be  formed.  The  sebaceous  glands,  Meibomian 
li^lands,  lachrymal  glands,  and  adrenals  are  especially  rich  in  fat.     It  oc- 


t?##t^ 


% 


Fig.  67.— Skin  with  sweat  Klaiuis,  from  the  sol 
oils  with  fine  fat  droplets;  h,  slender  L'land  coils  wit 
land  coils.     >;  :j90. 


•id.)     <i.  Thick  KlaiKJ 
Irops  lyiiit;  ahoiit  Ihu 


urs  to  a  lesser  ext<'nt  in  tlie  testicles  and  ovaries;  still  lcs.s  in  the  .salivary 
land.s,  thj^roid  and  sweat  glands  (Fig.  ^7,  a).  The  kidneys  have  the 
east  fat-content  of  any  of  the  glands.  Dnriiig  the  i)eriod  (if  lUiictioniil 
ctivity  rtesticles  and  ovaries)  and  in  advanced  age  tlie  f;it-('onl«Mit  is, 
a  general,  .somewhat  iiici-eased.     lii  the  testicles  mid   (»\:iiies  llie  fat   is 


196 


THE    RETROGRADE    CHANGES. 


found  both  in  tlie  epithelial  cells  and  iu  the  connective  tissue.  Further, 
the  fat-content  of  the  glands  is  very  constant  and  but  slightly  dependent 
ui»<)n  the  condition  of  the  general  nutrition,  so  that  it  does  not  disappear 
(luring  starvation  (Traina).  This  glandular  fat  may  then  be  designated 
as  the  permanent  fat  or  intrinsic  fat. 

The  liver  holds  an  especial  position  among  the  glands  in  so  far  as  fat 
is  ccuicerned.  As  do  the  other  glands  it  contains  constantly  a  certain 
number  of  line  fat-droplets  which  do  not  vanish  during  starvation.      In 


Fig.  68.— Fatty  liver  from  a  case  of  pulmonary  tuberculosis.     (Fleinmin?"s  solution,  safranin.)    a,i 
Central  portion  of  the  liver-lobule ;  b,  peripheral  zone  contaiuing  fat ;  c.periportal  connective  tissue.    X  30.1 


addition  there  also  occurs  a  temporary  storage  of  fat  which,   beginning! 
in  the  x^eriphery  of  the  lobule,  extends  toward  the  centre  as  aprogessive 
tilling  of  the  liver-cells  with  fat-di-oplets  (Fig.  68,  b)  ;  and,   finally,  thej 
liver-cells  may  become  completely  changed  into  fat-cells,  so  that  the  par-;; 
enchynia  acquires  a  straw-color. 

Fatty  infiltration  of  the  liver  may  result  from  excessive  food-supply, 
but  is  much  more  frequently  observed  in  marasmic  individuals,  particu- 
larly in  consumptives  whose  panniculus  is  atrophic.  Inability  on  the 
l)art  of  the  liver  to  destroy  or  to  give  off  again  the  fat  brought  to  it  from 
the  intestine  or  from  the  fat-depots  appears  to  be  the  cause  of  thi> 
phenomenon. 

Muscle-fibres,  surface  epithelium,  the  epithelium  of  different  gland-ducts. 
cartHage-cells,  connective-tissue  cells,  vascidar  endothelium,  leucocytes,  lympho 
cytes,  etc.,  show  a  variable  content  of  fat ;  but  all  contain  fat  without  show 
ingany  changes  that  can  be  regarded  as  degenerative  in  nature.  Ii 
individual  cases  it  is  evident  that  the  fat-content  is  dependent  upon  ai' 
alnindant  supply  of  fat  from  the  intestine  or  of  transportation  of  fat  frou 
the  fat-depots,  especially  in  those  cases  in  which  the  leucocytes  or  th< 
vascular  endothelium  (particularly  that  in  the  liver)  are  rich  in  fat.  Ii 
still  other  cases  there  are  definite  functional  conditions  (the  muscles 
during  which  a  rich  supply  of  fat  appears. 

The  spleen  and  the  lymph-glands,  with  the  exception  of  the  meseu 
teric  glands,  to  which  fat  may  be  brought  from  the  intestine,  contain  bu 


I 


FAT. 


'li  ill  fat,  parlicu- 


little  flit;  on  tlie  other  hand,  the  thymus  is  ivhitivcly 
hilly  at  the  time  of  its  <;reatest  deveh>pmen(. 

Ai!  animal  fats  are  mixtures  of  olein,  pahnitin  and  stearin,  that  is,  of  combina- 
tions of  oleic  acid  (Ci.Hs.O,),  stearic  acid  (C,.H;„-,()2)  and  palmitic  acid  (CoH:,,!)..) 
with  the  trivalent  alcohol  jrlycerin  (.C3H.-,[()II]:,)  to  form  neutral  esters,  the  so-called 
triglycerides.  Whether  taken  in  as  free  fatty  acids,  as  neutral  fats,  or  as  soaps,  tin; 
process  of  absorption  is  always  the  same;  they  appear  constantly  in  the  form  of  neut  ral 
fats  in  the  chann<>ls  through  which  alisorption  takes  place. 

In  close  relationship  to  the  l)ody-f;its  stand  the /(r/7/(///,v  (conibinat  ions  of  c.icli 
single  molecule  of  glycerin-phosphoric  acid  with  two  molecules  of  fatty  acid  and  the 
comi)lex  of  an  anunonium  base,  cholin),  the  protagons,  and  {\w  choh'stcrui'i.  substances 
which  occur  in  small  amount  in  the  most  varied  tissues,  Init  abundantly  in  the  myelin 
of  the  brain  and  the  peripheral  nerves.  Cholesterin  occurs  also  in  the  bile.  The 
breaking-down  of  all  the  components  of  the  lecithins  containing  neutral  fat  leads  first 
to  the  formation  of  fatty-phosphoric  acid,  which  is  then  split  into  fatty  and  glycerin- 
phosphoric  acids. 

The  fat  contained  in  the  human  organism  is  derived  primarily  from  the  food-fat 
taken  up  in  the  intestine.  In  the  early  weeks  of  life,  w'hen  the  intestine  of  the  nursing 
infant  is  still  abnormally  permeable,  the  finest  fat-droplets  are  taken  up  as  such  and 

carried   through  the  lymph- 

___      stream   into   the  blooll.      In 

later  life  the  taking  up 
unchanged  fat  through  tlie 
intestinal  epithelium  jjroba- 
lily  takes  place  to  a  very 
slight  degree  or  not  at  all, 
that  is,  the  fat  is,  for  the 
greater  part,  .si)lit  up  in  the 
ntestinal  canal,  and  through 


Fifi.  ti9,— Fiit-L'ranule  oelis  in  an  anfemii^  area 
brain.    (Marcbi"stluiii.)  a.  Fat-granule  cells;  /),  1 


y  the  epitheUum.  Even 
in  the  intestinal  epithelium 
these  soaps  are  changed  into 
herulesof  neutnd  fat  (just 
as  absorbed  peptone  is  again 
changed  into  albuminate)- 
The  glycerin  nec(\ssary  for 
this  change  is  absorbed  di- 
rectly from  the  intestine, 
where  it  is  present  in  a  free  state  arising  from  the  splitting  of  the  neutral  fats. 

In  the  entrance  of  the  fat  into  the  cells  of  the  fat-depots  the  fat-molecule  is  again 
split  up  and  then  reconstructed  within  the  cells. 

According  to  Arnold,  the  entrance  of  fat  into  the  cells  is  a.ssociated  in  many  ca.scs 
with  a  certain  activity  of  the  plasmosomes,  and  is  therefore  connected  witii  the  cell- 
granules,  which  he  regards  as  the  morphological  products  of  the  function  of  the  plas- 
mosomes. In  the  intracellular  fat-formation,  designated  by  him  as  granular  fat- 
I  synthesis,  which  occurs  in  leucocytes  and  lymphocytes,  also  in  endothelial  cells, 
: connective-tissue  cells,  cartilage-cells,  epithelial  and  gland  cells,  .soap  is  taken  into  the 
! cells  in  a  soluble  form  and  there  undergoes  a  granular  cliange  into  fat.  The  fat- 
jdroplets  appear  at  the  site  of  the  antecedent  granules. 

In  this  manner  there  arise  in  part  the  so-called  fat-granule  cells,  leucocytes  ami 
llymphocytes  clcsely  packed  with  fat-droplets,  that  occur  frecpiently  in  areas  of  necrosis 
'and  inflammation, 'particularly  in  the  central  nervous  .system  (Fig.  0!).  a).  According 
Ito  Arnold  the  uniform  size  of  the  fat-droplets  speaks  in  favor  of  such  an  origin.  Such 
granule-cells  may  also  be  formed  through  plKKjocfitdsis  ;  that  is,  the  am(el)oi<l  cells 
may  take  up  through  their  protoplasmic  movement  sfat-droi)lets  lying  free  in  t  lie  tissues 
(in  softening  of  the  brain  and  .spinal  cord  they  arise  through  the  disintegration  f)f  the 
medullary  sheaths).  In  the  event  of  such  occurrence,  chemical  and  morphological 
changes  in  the  material  taken  up  are  not  excluded. 

The  carbohydrates  form  a  second  .source  of  fat-formation  in  the  organism,  but 
the  chemical  processes  attending  the  formation  of  fat  from  carbohydrates  have  ncjt  been 
determined.     It  is  probable  that  the  amount  of  fat  .so  fonned  is  relatively  much  less 


19S  THE    RETROGRADE    CHANGES. 

than  the  fat  taken  in  as  such  from  the  food.  It  is  still  a  question  as  to  whether  fat  c:in 
be  formed  in  the  body  from  albumin.  Since  many  facts  speak  for  the  transformation 
in  the  animal  body  of  certain  <rrouj)s  of  the  albumin-molecule  into  glycogen  orgrapc- 
sugar,  the  theoretical  possibility  of  the  formation  of  fat  from  albumin  cannot  be  denied 
{Kraus). 

Of  the  fats  and  lecithins  present  in  the  organism,  those  containing  oleic  acid  alone 
reduce  osmium  tetraoxide  to  a  black  osmium  hydroxide,  so  that  treatment  with  osmic 
acid  or  Flemming's  solution  does  not  show  the  presence  of  palmitin  and  stearin.  On 
the  other  hand,  Sudan  III  and  Scharlach-roth  (ponceau)  stain  all  the  fats. 


Literature. 

{Fatiji  Infiltration. ) 

Arnold:   Fettkornchenzellen  und  Granulalehre.     Anat.  Anz.,  xxviii.,  1900;   Granuliire  j 

Fettsynthese.  lb.,  xxiv.,  1904;   Feinere  Struktur  der  Leber.  Virch.  Arch.,  16  Bd., 

1901;  Fettumsatz  und  Fettwanderung  in  der  Cornea.    C.  f.  a.  P.,  xiv.,  1903;   Gra- 

nulare  Fettsynthese.    Miinch.  med.  Woch.,  1903;  Fettumsatz  und  Fettwanderung. 

Virch.  Arch.,  171  Bd.,  1903. 
Aschoff:  Fettgehalt  fotaler  Organe.     Cbl.  f.  allg.  Path.,  viii.,  1897. 
Connstein:  Resorption  u.  Assimilation  der  Fette.     Med.  Woch.,  1900. 
Ebstein:  Die  Fettleil)igkeii  und  ihre  Behandlung,  Wiesbaden,  1892. 
Erb;    Dystrophia  muscularis  ])i()<rressiva,  Leipzig,  1891. 
Fischer;  Lipiimie  u.  Cliolcstorainie.     Virch.  Arch.,  172  Bd.,  1903  (Lit.). 
Fischler:  Exper.  erz.  Fettsynthese  am  iiberleb.  Organ.     Virch.  Arch.,  174  Bd.,  1903. 
Flemming-:  Bildung  u.  Riickbildung  d.  Fettzelle  im  Bindegewebe.     A.  f.  mikr.  Anat.^ 

vii..  1X70;  u.  V.  A.,  52  Bd.,  1871;   Hvpothesen  fiber  Fettresorption.     Mimch.  med. 

Woch.,    1898. 
Gaule:  Das  Auftreten  von  Fett  in  den  Zellen.     Arch.  f.  Anat.,  1890. 
Gautier:   Die  Erniihrung  der  Zelle.     Biol.  Cbl.,  xiv.,  1894. 
Hagemeister:  Fettbildung  u.  Fettsehwund  in   Abhang.    von    Zirkulation.     V.  A., 

172  Bd.,  1903. 
Herter-  Fettspaltung  u.  Fettaufbau  im  Gewebe.     Virch.  Arch.,  164  Bd.,  1901. 
Herxheiraer:  Fettinfiltration    u.  Fettdegeneration.     Ergebn.  d.    allg.    Path.,   viii., 

1904   (Lit.). 
Kaufmann:  L'origine  de  la  graisse.     Arch,  de  phys.,  viii.,  1896. 
Kisch:  Die  Fettleibigkeit,  Stuttgart,  1888;    u.  Eulenburgs  Realencyklop.,  art.  Fett- 

sucht.  1895. 
Kischensky :  Fettresorption  im  Darmrohr  u.  Fettransport.   B.  v.  Ziegler,  xxxii.,  1902. 
Lee:   l.'obesite,  Paris,  1886. 
Lindemann:  rel)er  pathologische  Fettbildung.     Beitr.  v.  Ziegler,  xxv.,  1899  (Lit.).! 
Munk:  Fette  u.  Fettsauren.     Eulenb.  Realencykl.,  vii.,  1895. 

Nasse:  Fettzersetzung  u.  Fettanhaufung  im  tierischen  Korper.     Biol.  Cbl.,  vi.,  1886, 
V.  Noorden:  Pathologie  des  Stoffwechsels,  Berlin,  1893;   Die  Fettsucht,  Wien,  1900. 
Oertel:  Kritisch-phys.  Bcsprech.  d.  Ebstein'schen  Beh.  d.  Fettleibigkeit,  Leipzig.  1885, 
Pawlow:  Die  Arbeit  der  Verdauungsdrusen,  Wiesbaden,  1898. 
Preiss:  Pspudohypertrophie  der  Muskeln.     Arch.  f.  Psych.,  xx.,  1889. 
Reviter:  Durchtritt  v.  Fett  durch  Darmepithel.     Anat.  Anz.,  xix.,  1901. 
Ruiiipf:   Fettgehalt  des  Blutes  u.  einiger  Organe.     Virch.  Arch.,  174  Bd.,  1903. 
Thaler:  I'ctt  u.  Krystalle  im  menschl.  Tcstikel.     B.  v.  Ziegler,  xxxvi.,  1904. 
Traina:   Fett  u.  Granula  bei  Mara.smus  u.  Hungerzustanden.     B.  v.  Ziegler,  xxxv., 

1904. 
Voit:   Plivsiologie    des  allg.  Stoffwechsels.     Hermanns  Handb.  d.  Physiol.,  vi..  1881 

rrsaclicn  <ler  Fet  taltlagerung  im  Korper,  1884,  u.  Biol.  Cbl.,  vi.,  1886. 
Winternitz:  Verlialteu  von  .lodfettcn  im  Organismus.     Z.  f.  ph.  Chem.,  24  Bd..  1S97 

.See  also   §    r^V,. 

jj  5().  Fatty  degeneration  ov /((l-niftdniorjthosis  is  th((f  condition  of  the 
crlJ.s  in  (rliich  J'al-drojilrl.s  appear  \\\  the  protoplasm  in  such  a  manner  as  to  indi- 
catra  chanf/f  in  I  la-  clninico-}dnjKiral  crll-.striid)irr.  In  a  part  of  the  cases  this  'i1 
clian.nv  may  be  inferred  from  the  ajipearance  of  the  cells,  in  that  fraji- 
iiientalion,  (lisinte.uration  (Fig.  70,  c,f),  and  separation  of  the  cells  from 
llicii  suLstinlnm  iiiav  be  demonstrated. 


\'^ 


FATTY    7)K(;t:XK1{  ATr(  ).V. 


100 


The  views  of  YirchoAV  were  formerly  accepted,  to  the  eflecfr  that  in 
lijxmiatosis  there  occurred  a  dcjjosit  of  fat  from  the  l)h)od  and  tissin-- 
jiiiccs;  wliile,  on  tlic  other  hand,  iii  fatly  de.nvncraliou  llicic  look  place 
a  formalioii  of  fat  li»m  llie  albumin  of  the  (U'i;-eiieratiiiii-  cells.  IJec<'iit. 
iuvestijiatious  make  the  latter  view  doubtful.  Althou.iih  the  ]K)ssibility 
of  a  formation  of  fat  from  albumin  cannttt  l)e  denied,  it  has  not  yet  been 
proved  that  this  is  the  case  in  the  so-called  fatty  deoenerat  ion  of  t'he<'ells. 

In  many  cases  what  we  call  fatty  de.i'enei-at"ion  "is  only  the  expression 
of  II  moJ  ceiiJ  a  r  physical  dccomtitutloii  of  the  cells,  a  fat -metamorphosis,  in 
which  the  fat  contained  in 
the  cells  in  a  form  that  can- 
not be  recognized  micro- 
scopically is  separated  out 
into  the  form  of  visible  drop- 
lets. Therefore,  an  increase 
in  the  actual  fat-content  of  the 
cell  does  not  occur  in  fatty 
degeneration.  Eenal  cells 
that  on  microscopical  ex- 
amination show  no  fat  may, 
nevertheless,  contain  twenty 
per  cent  of  fat.  Should 
fatty  degenei-ation  occur,  so 

that  the  fat  becomes  visible  in  the  form  of  droplets,  the  total  fat-conteut 
is  not  increased  (Eosenfeld,  Kraus).  A  process  similai-  to  that  taking 
place  within  the  body  occurs  during  the  autolj  sis  of  tissue  preserved 
aseptically  in  the  incubator,  fat-droplets  becoming  visible  in  such  tissues 
(Hansen,  Wentscher,  Kraus,  Miiller,  and  others).     When  fat  as  such  is 


,,«0«o 


Fig.  7i).— Fat-confiiining  livt 
cells,  n  and  h,  Fat-itifllti  ation ;  c , 
£,  /,  fatty  degeneration.    X  400. 


cie<i:eneration  of  the 
tieart-musL-le. 


I'k;.  72.  — Aiuemic  and  fatty  necrosis  of  the  myocardiiini  S5  lionrs  after  the  closure  of  a 
corouary  artery.  (Flemming's  solution,  safraiiin.)  a.  Necrotic;  b,  fatty  muscle  liljres;  c,  con- 
nective tissue  with  leucocytes  containing  fat.     X  300. 

not  present  in  the  cells  it  may  arise  through  a  chemical  deconstitution 
of  the  lecithin,  ccrrbrin,  and  ])rotaf/OHS  f  myelin)  contained  in  the  cells. 

A  second  source  of  the  fat  appearing  in  fatty  degeneration  is  the  fat 
hrour/ht  to  the  affected  cells  hi/  the  blood  and  tissue-juices,  arising  eitlier  from 


200 


THE    RETROGRADE    CHANGES. 


'^fllp  :^ 


^ 


Vi*-^,- 


'^ 


mil 


Fir.  73.— Fatty  defeneration,  va<n(>iiz;iti 
panization  of  theheart^muscle  ina  iiatimt  ilviiiL'-  from  \t\\>-\ 
inonia  and  nephritis.  (Flemming'.s,  .-,afiaiiiu.;  <;.  Trail 
verse  section  of  normal  muscle-cell ;  i/,  iimscle-i'ell  iu  a  .stai 
of  fatty  degeneration ;  muscle-cells  with  vacuoles;  c?,  ili 
organized  cell.    X  400. 


the  fat  contained  iu  the  food  or  transported  from  the  fat-depots  in  other 
tissues.  For  example,  in  phosphorus-poisoning  a  transportation  of  lat 
from  the  panniculus  to  the 
liver  takes  place.  It  is  also 
probable  that  the  same  thing 
occurs  in  other  intoxications 
(arsenic,  alcohol,  chloroform, 
oleum  pulegii).  In  such 
cases  au  increase  in  the  fat- 
content  of  the  affected  organ 
must  result,  but  this  is  not 
always  the  result  of  a  syn- 
thesis of  fat,  that  is,  of  a 
formation  of  higher  fatty 
acids  and  glycerin  and  their 
combination,  but  is  a  takiiig- 
up  of  fat  that,  either  as  such 
or  as  soaps,  has  been  given 
over  to  the  blood. 

In  the  couditiou  which  we 
call  fatty  degeneration,  the 
fat  appears  usually  in  the 
form  of  fine  droplets  (Figs. 
71,  72,  &,  73,  h,  and  74,  &),  but 
these  may  also  become  confluent  to  form  larger  drops  (Fig.  75),  particu- 
larly during  the  disintegration  of  the  cell  (Fig.  70,/).     The  conditions 

under  which  the  fat  of  fatty 
degeneration  appears  make 
it  probable  that  the  cSh 
ichichare  the  seat  of  the  fatty 
metamorphosis  are  still  living, 
hut  have  been  injured  by  ex- 
trinsic influences.  Iu  ana?- 
mic  infarcts  of  the  spleen, 
kidneys,  and  heart,  the 
fatty  cells  (Fig.  72,  b)  are 
found  in  the  zone  of  transi- 
tion between  the  necrotic 
(a)  and  the  living  tissue: 
that  is  where  the  circulation 
of  the  blood  and  lymph  is 
weakened  and  imperfect, 
but  has  not  ceased  entirely. 
The  appearance  of  fatt\ 
cells  in  glands  (Fig.  70,  c, 
d,  e,  /),  iu  the  endothelium 
of  tlie  blood-vessels,  or  the 
cells  of  the  heart-muscle 
(Fig.  73,  b)  occurs  in  in- 
toxications and  infections 
as  the  result  of  cell-in- 
jury through  toxic  action. 
Chnmic  fatty  degeneration  of  the  heart-muscle\Fig.  74,  b)  is  seen  in 
valvnlar  lesions,  i)ulmonary  emphysema,  general  ansemia;    in  the  renal 


m 


Kifi.  74.— Marked  fatty  degeneration  (chronic)  of  the  heart- 
muscle.  (Kleitiiiiinp's  sohitioii,  safranin.)  «.  Normal  nnjscle; 
h,  muscle  which  has  undergone  faity  degeneration.     X  80. 


i 


FATTY    DEGENERATION. 


201 


epithelium  of  consumptives  it  occurs  partly  as  the  result  of  a  (liiuiuished 
supply  of  oxyji'eu,  and  partly  as  the  action  of  \ox\c  subslaiices.  Kx- 
]>erinu'ntalinvestii;ations  have  shown  tliat  a  lon<;-continu<'(l  (Oexatiou  of 
the  body  temperature  leads  to  a  fatty  degeneration  of  different  tissues 
(heart,  kidneys,  and  liver). 

A  mild  S2:rade  of  fatty  degeneration  cannot  be  seen  with  the  nak<'d  eye. 
The  more  severe  forms  of  the  degeneration  give  an  oi)a(iue  whitish  color 
to  colorless  tissues,  as,  for  example,  the  intima  of  the  blood-vessels  an<l 
heart-valves,  whicli  frequently  show  patches  of  fatly  melamoiphosis. 
The  cortex  of  a  kidney  showing  fatty  degeneration  becomes   grayish  or 


^^^^^'^-^^ 


Fig.  75. — Fatty  degeneration  of  the  nnal  iiiithtlinin,  from  a  case  of  clironic  pulmonary  tuberfiilosis. 
(Formalin,  h;ematoxylin,  Sudan    III.)     X  300. 


yellowish  in  color.  In  the  heart-muscle  the  yellowisli  discoloration  of 
i  fatty  degeneration,  particularly  when  the  change  is  localized  in  small 
tfoci  (Fig.  74,  b),  stands  out  very  jiromiueutly  (''tiger-heart"). 

I  The  questions  relating  to  fatty  degeneration  have  during  recent  years  been  the 
.subject  of  diligent  researches,  and  these  have  shown  that  the  teaching  of  Virchow  of 
the  formation  of  fat  from  the  albimiin  of  the  body  can  no  longer  be  accci>ted.  'J'lie 
;  conclusions  resulting  from  recent  investigations  are  embodied  in  the  text  above. 
'<  Itisnotalwayspossible  to  decide  whether  the  fat  j)resent  corresponds  to  a  physio- 
jlogical  or  pathological  condition.  ^^  e  can  no  longer  accept  tlie  view  that  fine  droplets 
iof  fat  within  the  cells  signify  a  pathological  condition,  since  most  glands  contain  .<mail 
fat-droplets,  and  other  tissues,  for  example,  mu.scle-fibrcs,  also  contain  fat-droplets 
imder  normal  conditions.  In  favor  of  a  pathological  condition  speak  an  increa.se  of 
, fat-content  beyond  normal  limits  and  a  focal  occurrence  of  the  fatty  cliange. 
;  In  fat  transportation  the  fat  may  appear  in  the  blood  in  the  form  of  large  or 
[.small  droplets  (liptemia).  This  is  most  marked  in  the  ca.se  of  fat-metastasis  due  to 
itraumatic  lesions  of  adipo.se  tissue  leading  to  fat-eml)olism.  It  may  occur,  howe\'er, 
jimder  other  conditions,  as  after  the  abundant  absorption  of  milk  or  of  |)ure  fat  from 
jthe  intestinal  canal.  Large  fat-drops  that  remain  in  the  vessels  di.sappear  slowly,  in 
part  a.ssociated  with  an  increase  of  the  fat-content  of  the  neighboring  ti.ssue.  Further, 
proliferations  of  the  ves.sel-wall  may  occur  at  the  site  of  the  eml)olism,  not  only  after 
the  direct  introduction  of  fat  into  the  blood-vessels,  but  also  after  feeding  with  fat,  as 
la  the  administration  of  cod-liver  oil  (Wutti'g). 

If  fasting  dogs  are  fed  with  mutton-tallow,  there  is  a  deposit  of  nuitton-tallow  in 
the  fat  depots.  If  they  are  then  poi.soned  with  phosphorus,  oleum  pulegii,  or  phloridzin, 
their  livers,  which  show  fatty  degeneration  as  the  result  of  the  poLsoning,  are  found  to 
contain  mutton-fat  in  abundance  in  addition  to  the  animal's  own  fat  iRosenfel<l). 


202  THE    RETROGRADE    CHANGES. 

According  to  Leick  and  Windier,  the  mutton-fat  under  these  conditions  is  found  also  in 
the  fatty  heart-muscle.  In  dogs  fed  with  iodopin  and  afterward  poisoned  with 
])hosphorus,  the  iodized  fat  passes  into  the  liver.  In  animals  devoid  of  adipose  tissiu 
no  fatty  degeneration  occurs  in  the  liver  after  poisoning  with  phosphorus  or  phloridzin 
{Rosen/eld,  Fihiger).  ]^t 

In  the  case  of  aseptic  autolysis  of  the  liver  outside  of  the  body  Waldvogel  has  j 
recently  made  thorough  chemical  and  histological  investigations  that  seem  to  showi' 
that  fatty  and  fat-like  products  of  disintegration  may  arise  in  loco;  and  there  occurs  i 
an  increase  in  those  bodies  which,  related  to  albumin,  have  a  fat-like  (jecorin.  lecithin,  j 
protagon)  or  fatty  character  (fat-acids,  neutral  fat).  In  phosphorus-poisoning  (Wald- 
rogel  and  TitUemann)  protagon  and  jecorin  appear  as  disintegration-products  of  al- 
bumin (the  lecithin  present  is  for  the  greater  part  transformed  into  substances  which  i 
after  the  acetone  precipitation  make  up  the  residue  of  the  substances  soluble  in  ether).  ' 
A  similar  disintegration  of  the  albumin-molecule  occurs  in  autolysis. 

According  to  Dietrich,  a  formation  of  fat  does  not  occur  in  autolysis. 

In  degenerating  cells  (kidney,  inflamed  lung,  adrenals,  corpus  luteum,  •  i 
etc.)  doubly  refractive  droplets  similar  to  fat  are  found,  but  they  stain! 
only  slightly  Avitli  osmic  acid.  They  are  regarded  by  various  authors}  Hii 
(Albrecht,  Kaiserling,  Orgler,  etc.)  asm  i/el  in,  similar  in  character  to  the ;  i 
myelin  of  the  nerve-fibres.  It  is  also  probable  that  protagon  appears  in' 
this  form.     Such  droplets  also  appear  in  the  autolysis  of  cellular  tissues. ' 

The  kidneys  may  contain  less  fat  than  normal  and  yet  show  much  fat; 
both  to  the  naked  eye  and  on  microscopical  examination,  as  the  result  of  j  .j 
the  liberation  of  the  fixed  fat  in  fatty  degeneration.  The  invisible  fat  is!  i 
set  free  and  becomes  visible.  The  condition  of  fatty  degeneration,  which; 
is  a  well-established  anatomical  entitj",  may  be  defined,  therefore,  as  au 
infiUration  of  fat  from  outside  into  cells  degenerating  ihrojigh  the  inftnenee  of 
2)oisons  or  other  injurious  agents  (liver,  heart-muscle,  lyancreas)  or  as  a  setting 
free  of  the  invisible  intraceUuJarfat  through  autolysis  {kidneys,  s])leen,  muscle). , 


Literature. 

(Fatty  Degeneration  and  Autolysis.) 

Albrecht:  Myelinogene  Stoffe  im  Zellleben.     Verh.  d.  D.  path.  Cies.,  vi.,  1904. 
Beneke:  Fettembolie.     Beitr.  v.  Ziegler,  xxii.,  1897. 

Binz  u.  Schulz:  Kohlenoxydgasvergiftung.     Arch.  f.  exp.  Path.,  xiv.,  1881. 
Dietrich:  ICxperimente  z.  Fraged.  fettigen  Degeneration.     Miinch.  med.  Woch.,  1904. 
Dietrich  u.  Hegler;  Verand.  asept.  aufbew.  Organe.   Arb.  a.  d.  p.  Inst,  in  Tubingen. 

iy..   1904. 
Ehrlich:  Das  Sauerstoffbediirfnis  des  Organismus,  Berlin,  1885. 
Fibiger:  Die  Entwickelungd.  fettigen  Degeneration.     Nord.  med.  Ark.,  1901. 
Fischler:   Fettgehalt  in  Xiereninfarkten.     C.  f.  a.  P.,  xiii.,  u.  V.  A.,  170  Bd.,  1902. 
Frankel:  ImuAuss  d.  verminderten  Sauerstoft'zufuhr   auf  den  Eiweisszerfall.    Y.  A. 

ii7   Bd.,    1876. 
Handwerck:  Verh.  d.  Fettkorper  zu  Osmiumsaure  u.  Sudan.     Z.  f,  wiss.  Mikr.,  xv. 

1S98. 
Kaiserling  u.  Orgler:  Mvclm  in  Zellen.    Virch.  Arch.,  167  Bd.,  1902. 
Kraus,  Ribbert,   Albrecht,   Schwalbe,   Rosenfeld,   Orgler,   Dietrich,  Muller 

Fottdcgcneratiou  u.  Fcttinfiltration.     Verh.  d.  1).  path,  (les.,  vi..  Jena,  1904. 
Krehl:  I'ctligc  Degeneration  des  Herzens.     D.  Arch.  f.  klin.  Msd.,  51  Bd.,  1893. 
Landsteiner:  Tnibe  ,Schwelhmg.     Beitr.  v.  Ziegler,  xxxiii.,  1903. 
Leick  u.   Winckler:  Herkunft  d.   Fettes  bei  Fettmetamorphose    d.   Herzfleisches 

B.  f.  exp.  Path.,  48  Bd.,  1903. 
Leo:  Fettbildung  u.  Fetttransport  l)ei  Phosphorvergiftung.    Zeitschr.  f.  phvs.  Chemie 

ix.,   1885. 
Lindemann:  Ueber  pathologische  Fettbildung.     Beitr.  v.  Ziegler,  xxv.,  1899  (Lit.) 

Wirkunji  des  Oleum  Pulegii.     A.  f.  exp.  Path.,  32  Bd.,  1896,  u.  Z.  f.  Biol.,  39  Bd. 

1900;    Das  Fett  des  normalen  u.  des  fettig  entarteten  Herzmuskels.     Z.  f.  Biol. 

38  Bd.,  1899. 


fats:  ciioLKsTKinx.  20:5 

Lvibai'sch.;  Fettdegeneration  u.  Fottinfiltration.     Ergehn.  cl.  allj;.   Path.,  iii.,   1S97; 

\ertVttung  u.  Fettenibolie.     Jalirli.  v.  Eulenhurg,  ii..  190.S. 
Liikjanoff:  Vorles.  iiber  die  allgem.  Path,  dor  Zelle.  Leipzig,  lS?)o. 
Lummert:  Tierische  Fetto.     Pfliigers  Arcli.,  71  Bd.,  1S9S. 
Michaelis;  Milchsekretion.     A.  f.  iiiikr.  Aiiat.,  fA  lid..  ISOS. 
Miiller:    Hedfutung  der  Solhstverdauung.      Kongr.  f.  inn.  Med.,  xx.,  1902. 
Ribbert:   MorphoL  u.  ChiMii.  d.  fettigcn  Dogeneration.      1).  mod.  \\()C'h.,  19();{. 
Rosenfeld:  Organvorft'ttungcn.      Kongr.  f.  inn.  Med.,  xix.,  \\i('sl)ad('ii,  1901. 
Runge:   Die  Krankhciteii  der  crsten  Lehenstage  (akuto  Fcttdcgciifratioii).  Stuttgart, 

lS!i:^. 
Sacerdotti:  Knorpelfett.     Virch.  Arch..  ir)9Bd.,  1900. 
Sata;  Fotthilduiigdiirch  verschiedene  Baktericn.     Cbl.  f.  allg.  Path.,xi.,  1900;   lleber 

das  York,  von  Fett  in  der  Plant  u.  in  einigen  Driisen.     Beitr.  v.  Ziegler,  xxvii.; 

Pett  in  patholog.  Gewehen.     lb.,  xxviii.,  1900. 
Schmaus:  ^'ork.  d.  osmierten  Fettes  in  d.  Lelior  liei   Phosphorverg.     Altinch.  inecP 

Woch.,  1897. 
Starke:  I'eber  Fettgranula.     Arch.  f.  Anat.  u.  Phys.,  189.). 
Steinhaiis:  Morphologie  der  Milchabsonderung.     Arch.  f.  Anat.,  1892. 
Unna:  Xachweis  d.  Fettes  in  der  Haul.     Monatsh.  f.  prakt.  Derm.,  189S. 
Waldvog-el:   Aiitolyse  u.  fettige  Degeneration.     Virch.  Arcli.,  177  Bd.,  1904. 
Waldvogel  u.  Tintemann:  Phosphorvergiftung.     CbL  f.  allg.  Path.,  xv.,  1904. 
Wells:    riie  llclation  of  Autolysis  to  the  Histological  Changes  Occurring  in   Necrotic 

Areas.    Jour,  of  Med.  Res.,  1906;   The  Relation  of  the  Thyroid  to  Autolysis,  etc. 

Jour,  of  Biol.  Chem.,  1907. 
Wentscher:  Eigenlelien  menschl.  Epidermiszellen.     Beitr.  v.  Ziegler,  xxiv.,  1898. 
Werhowsky :  ^^■i^kun<J  erholiter  Eigenwiirme.     Beitr.  v.  Ziegler,  xviii.,  189,5  (Lit.). 
Weyl  u.  Apt:  Fcttgdialt  pathologischer  Organe.     Virch.  Arch.,  95  Bd.,  1884. 
Ziegler  u.  Obolonsky:  Ar.senikvergiftung  u.  Phosphorvergiftung.     Beitr.  v.  Ziegler, 

ii.,  1888. 

See  also  §  .5.5. 

§  57.  The  fats  which  occur  iu  the  human  body  consist  almost  entiroly 
of  a  mixture  of  the  glycerin -esters  of  oleic,  palmitic,  and  stearic  acids 
which  are  designated  olein,  palmiiln,  and  stearin.  The  lirst  is  fluid  at 
ordinary  temperatures,  the  second  melts  at  46°,  the  third  at  53°  (\ 
.Since  the  body-fats  contain  varying  proportions  of  olein,  i)almitin,  and 
{stearin,  they  \Avy  in  consistency  and  melting-point.  If  after  death 
[the  fat-containing  tissues  of  the  body  are  cooled  below  the  meltiiig- 
ipoint  of  the  contained  fat,  the  stearin  and  palmitin  may  separate 
(and  form  fine  stellate  or  feathery  needles  (Fig.  7(),  b,  c,  d),  which  are 
i commonly  called  margarin  needles,  and  which,  according  to  the  con- 
Iditions,  are  found  sometimes  in  fat-cells,  at  other  times  fi-ee  in  the 
tissue-lluids. 

Cholesterin  occuis  in  the  form  of  delicate  rhombic  i^lates  (Fig.  76, 
^0,  the  edges  aiul  corners  of  wliich  are  often  notched.  These  may  be 
found  wherevei-  there  are  formed  masses  of  <letritiis  ccMitaiiiiiig  lat,  aris- 
ing from  degenerating  cells  or  e.vtravasations  of  blood,  as  in  the  disea.sed 
Tunica  vaginalis  of  the  testis,  in  a  dilated  sebaceous  duct  or  gland,  oi-  in 
ja  softened  area  of  degeneration  in  the  wall  of  a  diseased  aorta.  "When 
jthe  substance  in  which  the  cholestei-in  plates  are  formed  is  Ibiid,  tliese 
may  often  l)e  visil>le  to  the  naked  eye  as  little  glistening  scales. 

Cholesterin  (C,JI,,0)  is  a  constant  constituent  of  the  l)ile,  and  is 
furnished  by  the  nincons  membrane  of  the  gall-bladder  and  bile-dtu-ts, 
and  held  in  solution  by  the  l)ih'  salts  and  soaps.  It  is  fonnd  also  in  tlie 
Jiiednlla  of  the  nei\  e-libres,  and  in  small  amounts  in  tlii^  blood,  where  it 
is  held  in  solution  by  fats  and  soaps.  According  to  JJniciiard  traces  (»!' 
cholesterin  are  found  in  all  the  organs. 

Cholesterin  is  insoluble  in  water,  dilute  acids,  caustic  alkalies.  :ind 
cold  alcohol ;  it  is  soluble  in  boiling  alccthol,  etiier,  choloruroini,  an<l 
iienzol. 


204 


THE    RETROGRADE    CHANGES. 


Wheu  treated  with  a  mixture  of  five  parts  of  concentrated  sulplinric 
acid  and  one  part  of  water  the  edges  of  cholesterin  crystals  take  on  a 
carmine-red  color,  which  gradually  passes  into  violet.     Sulphuric  acid 


,y 


A^- 


d  ^',' 


^h'MiM 


r^^ 


Fig.  76.— rt,  Cholesterin  plates;  7),  free  cluster  of  margarin  needles ;  c.  needles  enclosed  within  fat-oells ; 
d,  grass-like  bunch  of  margarin  needles.    X  300. 


and  water  mixed  in  the  proportions  of  three  to  one  give  a  violet  color  to; 
the  edges  of  the  crj^stals.  Concentrated  sulphuric  acid  containing  a  trace.' 
of  iodine  colors  the  crystals  violet,  blue,  green,  and  red.  I 

The  origin  of  cholesterin  is  not  known  with  certainty.  It  is  probable j 
that  it  is  an  intermediate  product  in  the  decomposition  of  albumin.  Cor- 1 
responding  to  this  view,  it  is  found  under  those  pathological  conditions} 
in  which  albuminous  substances  break  down  with  the  formation  of  fat. 


Literature.  i 

{Cholesterin.)  ' 

Hoppe-Seyler :  Handb.  d.  physiol.  u.  path.-chem.  Analyse,  v.  Aufi. 

Munk:  Art.   Cholesterin.     Euleuburg's  Realencyklop.    u.  Eulcnburg's  Jahrbucli,  i., 

is'ji.  : 

Windaus:  Ucber  Cholesterin,  Freiburg  i.  B.,  1903. 

VII.  The  Deposit  of  Glycogen. 

^  5S.  Glycogen  (C„H,„0  j"  is  a  carbohydrate  which  is  readily  con- 
vertible into  sugar;  and  in  the  body  is  formed  chiefly  from  the  carboliy 
drates  of  the  food,  but  may  also  be  formed  from  albumin  and  gelatin. 

lu  the  tissues  of  the  body,  glycogen  is  found  as  a  hyaline  .substance,  mosi 
often  within  the  cells,  but  occasionally  in  the  tissue-spaces.  It  usuall\ 
occurs  in  the  form  of  spherules  or  lumps  of  different  sizes.  In  the  cell-, 
these  spherules  are  most  frequently  found  in  the  neighborhood  of  tin' 
iniclcns. 

(Jlycogen  is  soluble  in  water,  but  the  solubility  of  that  found  in  dif 
ferent  tissues  varies  (Langhans)  ;  that  found  in  the  liver,  kidneys,  mus 
cles,  and  pus-corpuscles  is  more  easily  soluble  than  that  of  ciirtilage' 
cells  and  surface  epithelium.  Fixation  of  the  tissue  in  alcohol  render; 
llie  glycogen  less  soluble  in  water.  After  death  the  glycogen  of  the  live 
is  quickly  converted  into  sugar  through  the  action  of  a  diastatic  ferment 

Gfi/coffeu  becomes  brownish-red  when  treated  icith  iodine.      Through  : 


I 


GLYCOGKX. 

method  given  by  l>('sl,  glyco<2,('u  may  also  bo  stained   re(l\\illi   < 
(Fig.  77,  />,  (■). 

Glycogen  is  ])resent  in  almost  all  the  tissnes  of  the  embryo, 
the  iVetal  membranes  at  an  early  period  of  develoi)meut;  and  in  tl 
body  in  the  liver-eells,  muscles,  heart-muscle,  cartilage-cells,  in  t 
face  epithelium  of  various  organs,  in  the  leucocytes,  and  in  the 
serum  ((Jabiitsche\vski ).  During  slarxation  the  glycogen  of  the 
diminished,  and  under  iiatliological  eondilions  may  Miiolly  disap 

(rJi/<'oi/<ii  <ij>j)r<irs  ill  p(it/infof/ic((//i/  iiicrcdsrd  anion  ill,  ])arli(*idarl\ 
betes,"  ehielly  in  the  l)l()<)d  and  in  the  kidneys.      Tl  "    " 


205 


•pit  licliui 


also  m 
le  adult 
he  SU1-- 
blood- 
li\('i'  is 
(ear. 
in  dia- 
of   the 


Fig.  77. — Glycotren  degeneration  of  the  renal  epithelium  in  a  case  of  diabetes.  (Compare 
Gierke,  1.  c.)  a.  Normal  tubules;  b,  epithelium  with  early  stage  of  glycogen  deposit;  c,  advanced 
;:!ycogen  depcsit  with  epitlielial  destruction.      X  300. 

renal  tul)ules  in  certain  areas  contains  in  part  huge  lunnbers  of  small 
[irops  (  Fig.  77,  h),  and  in  part  also  large  drops  (c).  Since  this  dei)Osil 
leads  tinally  to  a  destruction  of  the  cells,  the  C(mditiou  nuiy  be  desig- 
nated as  a  glycogen  degeneiation  of  the  cells. 

Glycogen  occurs  also  witiiin  inllammatory  foci  (also  in  infections  i)i()- 
iferations  of  granulation-tissue  [Gierke]),  usually  first  in  the  poiy- 
nudear  leucocytes,  but  also  in  the  so-called  e[)ithelioid  cells,  fibroblasts. 
Old  the  syncytial  giant-cells  developing  fi-om  these,  fnither  also  in  the 
issue  bordering  upon  the  inflammatory  ai'ea.  (Jlxcogen  is  also  fonnd  in 
nany  tumors,  carcinomata  and  sarcomata. 


It  is  (liliicult  to  determine  the  significance  of  the  glycogen  appearing  under 
>athoiogical  conditions.  Since  glycojjjen  is  al)iin(lant  in  eniliryonal  tissues  and  in 
liuickly  firowing:  tumors,  Brault  is  of  the  oijinion  that  its  appearance  is  a  sijjn  of  an 
hcreased  proliferative  cell  activity;  but  tlie  presence  of  glycoKen  in  larpe  amounts  in 
|-us-cells  does  not  agree  with  this  theory.  .Nbjreover,  in  ttniiors  it  is  not  found  in  the 
jegions  of  most  active  cell  proHferation.  According  to  (licrke,  glycogen  appears  l)y 
'.reference  in  those  tissnes  deprived  to  a  certain  extent  of  the  circulation.     A  certain 


206  THE    RETROGKADE    CHANGES. 

parallel  exists  between  the  occurrence  of  fatty  degeneration  and  glycogen  deposit. 
Both  changes  are  found,  for  example,  in  inflammatory  foci  and  at  the  edge  of  necrotic     il 
areas.     In  both  cases  degenerating  cells  are  present  that  are  able  to  take  up  both  fat 
and  glycogen,  but  can  no  longer  change  them. 

According  to  Wolff,  the  leucocytes  circulating  in  the  normal  blood  also  contain 
glycogen,  but  this  gl^ycogen  is  very  easily  soluble,  and  therefore  difficult  to  demonstrate. 
In  many  infections  and  inflammatory  exudates  the  glycogen  of  the  leucocytes  becomes 
less  soluble  and  can  therefore  be  more  easily  demonstrated. 

The  iodophile  hyaline  substance  contained  in  the  tissues  is  not  a  pure  glycogen, 
but  is  most  probably  a  combination  of  glycogen  with  an  albumin-like  substance.     To 
avoid  the  solution  in  water  of  glycogen  in  fresh  preparations,  a  syrupy  solution  of  I] 
iodine  in  gum  {Ehrlich)  or  iodine-glycerin  (Barfurth)  may  be  used  in  this   investiga- 
tion.    Sections  of  tissues  hardened  in  alcohol  are  best  treated  (Langhans)  with  a  dilute 
tincture  of  iodine  (1  part  tincture  iodine  to  4  parts  absolute  alcohol),  and  then  cleared  in 
oleum  origani  in  which  the  reaction  is  preserved  for  a  long  time.     The  reaction  is  also 
preserved  for  a  long  time  in  hard  Canada  balsam.     For  the  staining  of  glycogen  with 
carmine,  Best  gives  the  following  method:    the  sections  are  first  stained  with  ha^ma- 
toxylin  and  are  then  stained  for  three-fourths  to  one  hour  in  a  mixture  of  two  parts  of 
a  solution  of  carmine  (carmine  1.0  grm.,  ammonium  chlorate  2.0  grms.,  lithium  car-   : 
bonate  0.5  grm.,  aq.  dest.  50  grms.,  brought  to  a  boiling-point,  after  which  there  is  ] 
added  20  c.c.  of  liq.  amnion,  caust.),  3  parts  of  liq.  am.  caust.  and  6  parts  of  methyl 
alcohol.     They  are  then  decolorized    for   a    few  minutes    in   a   mixture    of   2   parts   > 
methyl  alcohol,  4  parts   absolute  alcohol,  and  5  parts  water,  and    finally  mounted 
in  Canada  balsam. 

Literature. 

Barfurth.:  Histochem.  Untersuch.  iiber  das  Glykogen.     Arch.  f.  mikr.  Anat.,  25  Bd.,   ' 

1885.  _  i 

Best:  Ueber  Glykogen,  inspes.  bei  Entziindung.     Beitr.  v.  Ziegler,  xxxiii.,  1903.  j 

Brault:  Glycogenese  dans  les  tumeurs.     Arch,  des  sc.  med.,  1896;  La  production  du   ; 

glycogene  dans  les  tissus  qui  avoisinent.     Arch.  gen.  de  med.,  1899;  Le  pronostic     ! 

des  tumeurs.     L'ceuvre  med.-chir.,  1899.  j] 

Butte:  La  fonc'tion  glycogenique  du  foie  dans  quelques  maladies.     Arch,  de   phys.,   i 

1891. 
Czerny:  Zur  Kenntn.  d.  glykogenen  u.  amyloiden  Entartung.     Arch.  f.  exp.  Patli., 

33  Bd.,  1893. 
Driessen:  Unters.  fiber  glykogen reiche  Endotheliome.     Beitr.  v.  Ziegler,   xii.,   1892.   '■ 
Ehrlich:  Glykogen  im  diabetischen  u.  im  norm.  Organismus.     Zeit.  f.  klin.  Med.,  vi.,   i 

1883.  '  _  ; 

Fichera:  Yerteilung  der  Glykogen  bei  Glykosurie.     Beitr.   v.   Ziegler,  xxxvi.,   1904   . 

(Lit.). 
Gabritschewski:  Glykogenreaction  im  Blute.     Arch.  f.  exp.  Path.,  28  Bd.,  1891. 
Gierke:  Glykogen  in  d.  Morphologic  d.  Zellstoffwechsels.     B.  v.  Ziegler,  xxxvii.,  1905.   ; 
Hamniarsten:  Physiologische  Chemie,  Wiesbaden,  1899.  ' 

Kaminer:  Glykogengehalt  der  Leukocyten.     Verb.  d.  anat.   Ges.,  1902;    Z.  f.  klin.  | 

Mod.,  47  Bd.,  1902.  j 

Katsurada:  Glykogen  unter  pathol.  Verhaltnissen.     B.  v.  Ziegler,  xxxii.,  1902.  '■ 

liOeper:  Le  glycogene  dans  le  sang.     A.  de  mM.  exp.,  1902.  | 

Langhans:  Glykogen  in  pathol.  Neubildungen  u.  Eihauten.     Virch.  Arch..  120  Bd.,  i' 

IS'.tO.  \ 

V.  Mering:  Zur  Glykogenbildung  in  der   Leber.     Pfiugers  Arch.,  xiv.,  1877;    Ueber 

1  )ial)ctes  mellitiis.     Verb.  d.  VI.  Congr.  f.  inn.  Med.,  Wiesbaden,  1887. 
Nebelthau:  Glykogenbildung  in  der  Leber.     Zeit.  f.  Biol.,  28  Bd.,  1892. 
Pfliiger:   Glvkogen.    Pfliigers  Arch.,  96  Bd.,  1903  (Lit.).  1 

Reich:  f  llvkogen  Roaktion  des  Blutes.     Beitr.  v.  Bruns,  42  Bd.,  1904  (Lit.).  i 

Wolff:   Zur  Los.  d.  (Jlykogenproblems.     Z.  f.  klin.  Med.,  51  Bd.,  1904. 


MUCOID    DKGEXKKA'I'IOX, 


207 


Vin.  riucous  Degeneration. 


Ill  the  umbilical  cord  the 
a         bar 


§  T)!).  riucous  degeneration  lias  i(s  i)liysi(>l()<;i<'al  prototype  in  the 
production  of  uiucus  by  the  mucous  membranes  ami  mucous  <;l:nids,  ami 
in  the  formation  of  mucus  in  llie  conn('cti\e  tissue  of  the  umliilical  cord, 
tendons,  bursa?,  and  synovial  membranes, 
mucus  occurs  as  a  jelly-like  matrix ;  in  the 
joints,  bursa',  and  tendon-sheaths  it  foi-ms 
a  clear,  striufiy  lluid. 

In  the  epithelium  of  the  mucous  mem- 
branes the  mucus  a])pears  tirst  in  the  .ii'ob- 
let-cells  (Fig.  78,  a),  forming  a  clear  sub- 
stance which  stains  with  hjcmatoxylin.  In 
mucous  glands,  during  the  pi'ocess  of  mu- 
cus fornuition,  the  epithelial  cells  swell, 
their  central  portions  become  clear,  and 
I  he  granules  of  the  i^rotoplasm  are  re- 
iduced  to  small  groups  or  strands.  The 
■lo-called  mucous  corpuscles  of  the  saliv- 
uy  secretion,  which  are  characterized  b,7 
glassy,  transparent  contents  and  vibrating 
protoplasmic  granules,  are  round  cells 
uvhich  have  undergone  mucous  degeuer- 
ition. 

I  The  mucus  formed  from  the  protoj^lasm 
:>f  the  cells  may  be  discharged,  and  the 
•ells  remain  intact,  or  in  other  cases  they 
nay  be  destroyed. 

;Mucus  is  produced  in  the  same  way 
inder  pathological  conditions  as  under  nor- 
iual  (Fig.  78,  a).  In  catarrh  of  the  nuicous 
!iieml)ranes  there  is  an  increased  formation 
if  nuicus  by  the  cells  of  the  superficial  epi- 

;helium  as  well  as  those  of  the  glands.  In  addition  thr  ])us-c<>r]uiscles 
imy  also  undergo  mucous  degeneration,  tlu^  mncin  being  formed  I'lom 
he  miclein  of  the  nuclei  (Kossel).  In  mucous  membianes  co\ei-ed  with 
ylindrical  cells  the  number  of  goblet-cells  is  increased,  and  in  the  secre- 
ion  there  are  found  cells  which  have  undergone  comi)lete  mucous  degeu- 
ration — that  is,  they  have  been  converted  into  glassy  masses  containing 
e\v  granules.  Other  cells  contain  the  mucus  in  the  form  of  drops  of 
arying  size. 

\  The  epithelium  of  pathological  tissues  jnay  also  undergo  a  mucous 
legeneration,  in  a  manner  similar  to  that  occurring  in  normal  tissues, 
fhus  the  epithelial  lining  of  cysts  of  the  ovary  and  of  intestinal  tumors 
lay  often  contain  numerous  goblet-cells  (Fig.  71>,  a),  and  cells  which 
ave  undergone  total  mucous  degenei-ation  (/>).  In  the  so-called  gelat- 
ions or  mucoid  carcinoma  (colloid  caicinoma)  a  large  part  of  the  epi- 
lelial  cells  suffer  a  mucous  metanioi'])hosis. 

Of  the  connective  tissues,  which  may  snfler  a  mucous  degeueration  and 
lereby  acipiire  a  gelatinous,  transi)arent  appeaiance,  may  be  mentioned 
brous  connective  tissue,  also  caitilage,  bone,  adipose  lissn(\  bone  mar- 
jw,  and  sarcomatous  tissue.     In  these  tissues  it  is  cliielly  the  ground- 


m::B^-sm^ 


no  78  —Formation  of  niunis  within 
he  (pithtlial  <('ll>,  of  ,in  <ifl(  nuiiiatous 

ll)l\pof  tllO    SMI  ill     llltl  stIllC         l\l(Ol)Ol, 


Ppllll.  Il 

III!      With 

towlllU 

-Hops    of 

s        /,      fl, 

(    lIMKUs; 

208  THE    RETROGRADE    CHANGES. 

substance  (Fig.  80,  b)  which  undergoes  mucous  change  and  is  converted 
into  a  homogeneous,  structureless  mass.  The  cells  may  remain  un- 
changed, or  may  become  fatty,  or  also  undergo  mucous  degeneration.. 
In  the  last  e\'ent  the  entire  tissue  ultimately  forms  a  hyaline  mass,  in 


FIG.  80. 

FIG.  7'j.— Epithelial  cells  whk-li  have  undergone  raueous  degeneration,  from  a  cystadenoma  of  the  ovary. 

a,  Cells  showing  slight  change;  h,  cells  showing  marked  degree  of  mucous  change.    X  40ii. 

Fig.  80.— Mucous  degeneration  of  the  connective  tissue  of  the  aortic  valves  (osmic  acid,  glycerin),   o, 

Fibrous  tissue ;  b,  myxomatous  tissue.    X  350. 


which  only  scattered  fibres  of  connecti-^-e  tissue,  or  single  cells  or  groups 
of  cells  are  left  to  suggest  the  original  tissue. 

The  stringy,  or  gelatinous  material,  which  results  from  mucous  de- 
generation, does  not  represent  a  single  chemical  substance;  in  it  there 
may  be  found  different  varieties  of  mucins  as  well  as  of  pseudomucins. 

The  mucins  (submaxillary,  intestinal,  and  tendon  mucin)  are  nitro- 
genous substances  somewhat  resembling  albumin.  They  dissolve  or 
swell  np  in  water  forming  a  stringy,  mucous  fluid,  from  which  they  may 
be  precipitated  in  a  stringy  form  by  means  of  alcohol  or  acetic  acid ;  but 
differ  from  the  true  albumins  in  the  fact  that  the  jirecipitate  is  not  redis- 
sohed  in  an  excess  of  the  acid.  The  precipitated  mucins  are  soluble  in  ; 
neutral  salt-solutions,  caustic  alkalies,  and  alkaline  carbonates ;  and  are 
gradually  converted  into  alkali-album inates  in  case  of  solution  by  thei 
last  named. 

All  mucins  contain  nitrogen  and  sulphur;  their  content  in  carbon,  * 
oxygen,  nitrogen,  and  sulphur  varies  in  the  different  forms. 

Pseudomucin  also  dissolves  in  water,  foi-ming  a  gelatinous  fluid,  ; 
from  which  it  may  be  precipitated  in  stringy  masses  by  alcohol.  Thei 
l)r('('ipilale  ivdi.ssolves  in  water.  Solutions  of  pseudomucin  are  not  pre-  j 
cipilated  )»>•  acetic  acid. 

Pseudomucin  is  found  particularly  in  ovarian  cystomata,  and  is  the 
cause  of  the  gelatinous  character  of  the  cyst -contents.  It  is  produced 
by  the  epithelium  of  these  tumors  (Fig.  79) ;  and  in  its  formation  the 
same  changes  take  place  in  the  cells,  as  in  the  formation  of  mucin  fromj 
e]>it helium.  In  all  probability  the  mucous  substance  present  in  gelat-j 
intms  carcinoniata  is  a  body  closely  related  to  pseudomucin  or  metalbu 
min — that  is,  tiicic  are  diiferent  varieties  of  pseudomucin  (Pfanneustiel); 
of  which  the  two  mentioned  aie  examples. 

Tliroiigli  ])ro]icr  IrcaluK'nt  the  rnxcins  may  be  split  into  a  carbohydrate,  animal, 
gum  (Lundwehr,  Jl(imnuirstcn),  and  nuicin  may  therefore  be  designated  a  glycoprotein       •>: 
{Pjunnenatiel).    Tlic  /i.v>n/n„inri,is   when  treated  witli   dihite    mineral   acids    lilvcwise;' 
split  off  a  carbohydrate  whicli  reduces  copper   sulphate  in  alkaline  solution  (f!/o«-i'i tij i 
7icns(H).  m:>^ 


EPITHELIAL    IIYALIX. 


209 


The  mucin-like  substances,  prccipitablc  by  acetic  acid,  which  occur  in  the  ftijnoridl 
flxid,  dilTer,  according  to  Salkowski,  from  nucleoulbumin  in  the  absence  of  phosi)horus. 
From  ordinary  mucin  tiicy  are  distiniiuislicd  by  tlieir  dilVerent  behavior  with  mineral 
acids;  when  boiled  with  dilute  hydroeliloric  acid  no  reducing  substance  is  obtained. 

Mi fj II ktijf' has  (obtained  from  the  gelatinous  contents  ol'  an  ovarian  cyst  a  nuu  indike 
substance  which  he  has  named  pammucin.  It  dillers  from  pseudomuciu  chietiy  in  the 
fact  tiiat  without  previous  boiling  with  dilute  acids  it  reduces  copper  oxide  in  an  alka- 
line solution. 

Literature. 


ir.,  1864. 
Arch..  ;}( 


2C,  l?d., 


,  1891. 

phys.  Chem., 
39  Bd.,  u.  40 


(^Fkcoks  Dcgcncmtlon. ) 

Eichwald:  Die  Kolloidentartung  der  Eierstocke.     Wiirzburger  med.  Zcits 
Hammarsten:  Studien  liber  ]\Iucin  u.  mucinahnliehe  Substauzen.     PlU'u 

Hd..  18S,j. 
Hoppe-Seyler :  Ilandb.  d.  phys.  u.  pathol.-chem.  Analyse,  5.  Aufl. 
Hoyer:  jS'achweis  d.   Mucins  durch  Filrbemethoden.     Arch.   f.   mikr.  Anat., 

1890. 
Kossel:  Ueber  Schleim  und  schleimbildende  Stoffe.     Dent.  med.  AVoch. 
Landwehr:  Ueber   ]Mucin,  ^Metalbumin,   u.   Paralbumin.     Zeitschr.    f. 

viii.  ;  Uel)er  die  Bedeutung  des  thier.    Gummis.      Pfliiger's  Arcli., 

Bd..  1887. 

Leathes:  Beitr.  z.  Cliemie  d.  Ovarialmucoide.     Arch.  f.  exp.  Path.,  43  Bd.,  1899. 
Mitjukoff:  Ueber  das  Paramucin.     Arch.  f.  Gyn.,  49  Bd.,  1895. 
Pfannenstiel :  Pseudomucine  d.  cystischen  Ovarialgeschwlilste.     Arch.   f.   Gyn.,   38 

Bd.,  IS!)0. 
Salkowski:  Zur  Kenntniss  der  Synovia.     Virch.  Arcli.,  131  Bd.,  1893. 
Struiken:    Histol.   u.  Histochemie  d.   Bectumepithels  u.   il.   Schleimzellen.      Inaug.- 

Diss.,  Freiburg,  1893. 

IX.   Formation  of  Epithelial  Colloid  and  Epithelial  Hyaline 
Concretions. 

^  60.  The  epithelial  formation  of  colloid  is  a  process  closely  related 
to  the  epithelial  production  of  inuciis;  it  consists  partly  in  a  secretion  of 


SL— Colloid  in  enlarged  thyroid  gland.     (Alcohol,  hasmatoxylin.)    a.  Follicle  filled  with  cells;  7*,  foU 
!»■  showing  lumen;  c,  masses  of  colloid  ;  (?,  capillary;  e,  connective-tissue  septum  with  artery.    X  (10. 


-Secretion  of  colloid  in  the  thvt 


(.\fter  Hozzi.i     <(,  Colloid; 


with  granules. 


'oUoid  by  gland-cells,  and  ])artly  in  a  conversion  of  entire  cells  into  col- 
joid.     Physiologically,  colloid  is  found  in  the  thyroid  (Fig.  82),  where  it 
14 


210 


THE    RETROGRADE    CHANGES. 


m 


¥ui.  83.— liilated  urinary  tubules  filled  with  colloirl 
fluid,  liffiinatoxylin,  and  eosin.)     X  250. 


appears  in  the  form  of  hyaline,  rather  firm,  eolorless,  or  slu/hfli/  eolored, 
jelly-like  manses,  which  in  the  tirst  place  lill  the  follicles  (c),  bnt  from 
these  \\v<\\  extend  into  the  lymph -vessels  of  the  thyroid.     Faihologieal 

eoUeetions    of    eolloid     occur 

both  in  normal  gland-tissnc 

and  in  newly-formed  gland- 

ular-tissne    of    pathological 

iial  nre.     The    accamulatioii 

causes  a  more  or  less  marked 

/it^^HiKv'         i^^'^'^^liy^  v'""      <^listention    of    the    follicles, 

'll^^^^^^;        ^<  *       ''^'"'/t^a^^'^  and  thereby  leads  to  an  en- 

I'j^^BB^sW'^*^  V'^''^        ^,**-''  largement  'of    the    affected 

.- .     .  -?      -.  .        ,  colloid  goitre  or  bronchocele. 

The  typical  secretion  of 
colloid  is  characterized  l)y 
the  formation  of  homoge- 
neous granules  and  spherules 
iu  that  portion  of  the  epithelial  cells  next  to  the  lumen  of  the  follicle 
(Fig.  82).  Some  of  the  cells  may  be  completely  filled  with  these  gran- 
ules. In  excessive  and  atyi^ical  formation  desquamated  cells  may  be- 
come converted  into  the  hyaline  substance  of  colloid. 

The  colloid  of  the  thyroid  is  found  on  microscopical  examination  to 
be  hom(>f/e)te(n(s ;  aud  according  to  its  appearance  it  maybe  designated 
epithelial  hyalin.  As  a  rule  it  incloses  no  cellular  elements,  bnt  de- 
generating cells  may  be  found  in  it.  Alcohol  and  acetic  acid  cause  no 
clouding,  or  precipitation  in  the  form  of  threads,  as  happens  in  the 
case  of  ]nucin  when 
so  t  r  e  a  t  e  d .  By 
means  of  Van  Gie- 
son's  staining  meth- 
od the  colloid  is 
stained  orange-red, 
while  the  (connec- 
tive tissue  takes  a 
fuchsin-red.  It  must 
1)0  noted  tliat  the 
eontenls  of  tlie  thy- 
loid  follicles,  which 
are  designated  col- 
loid, are  not  always 
of  tlie  same  chai-ae- 
ler.  At  oiu^  time 
1  lu^  snbstanc(ns  fi)-m, 
at  aiiollier  soft  or 
ev<'n  lluid,  or  at  least 
is  i-eadily  soln])le  in 

water.     ]n  ])re])ara-  i 

tions  fixed  iu  alcohol  a  gi.inulation  orclea^age  ma>  be  cuised  b_\  con- 
traction ;  and  the  staining  reactions  are  not  always  the  same.  ■ 
The  chemical  nature  of  the  thyroid  colloid  is  not  fully  known,  and  it 
is  ])robable  that  the  contents  of  the  follicles  are  of  variable  composition. 
It  is  most  probably  an  albuminoid  body  which  is  combined  with  iodothy- 
rin,  the  active  principle  of  the  thyioid  gland. 


i 


I  I(t  s4-((>1Ioi(1  (onddions  in  the  (N^Ik  dii.ittd  tulmUs  i>f 
iiunn  (loniialm,  \an  dieson  s  stain  )  a,  h,  dland-tubiih 
iM(\aiiuni,  (,  (\stb(ontaiiiing((in(ii(l  (omittions  ((/)      ^  S(i 


KPITHKLIAI.     inALlX:    COLLOII). 


!U 


Kpitlu'liiil  liyalin  is  also  foiiiul  in  tlic  .ulaiuls  of  the  liypopliysis  I'on'- 
hii,  ill  tlu'  uriiiai y  tubules  of  diseased  ki(iiieys  (Fii;-.  s;>),  in  the  prostate 
(Vvj;.  ^5,  J),  in  cysts  of  the  i)arovariiim  (Fii;-.  84,  d),  in  thei;lands  of  the 
stoiiiaeh,  and  more  I'arely  in  other  .ulands.  In  the  last-nain«'d  oi;L;ans  (he 
hyalin  oceurs  in  the  f(»rm  of  a   iinifoinily  lioinogeneons  mass  (•oin])letely 


Fig.  85.— Pei'tion  from  a  liypeitrophie  prostate  with  concretions.     (Miiller'.s  fluid,  Iuvmh; 
(/,  struma  ;  h,  jrlanils  ;  c,  dilated  glands;  (',  ((incretiuiis.     >;  4-'). 


ii.aiidecMiii.) 


lilliiiji;  tlie  gland-lumen,  or  often  as  hyaline,  in  ])ai(    laminated  concre- 
tions (Fig.  84,  il,  and  Fig.  85,  d)  of  more  or  less  tinn  consLsteiicy. 

It  miLSt  not  be  assumed  that  the  last-named  formations  are  ideniical 
jiii  their  chemical  comi)ositiou  with  thyroid  colloid.  The  only  thing 
[which  they  po.sse.s.s  in  common  is  this:  they  both  represent  tramfnnnrd 
\protoplasm  of  ghind-ceUs — a  substance  v.hich  is  lujidine,  x^osseases  a  certain 
[lirinness,  and  does  not  react  to  ehem'tcal  reaoeids  in  the  same  niainier  as  dots 
\muci)i.  These  concretions  may  also  undergo  changes  MJiich  necessitate, 
on  their  part,  a  different  behavior  toward  microchemical  reactions. 
iThis  is  particularly  true  of  the  prostatic  concretions,  Avhich  not  infre- 
huently  show,  when  treated  with  iodine,  a  reaction  that  has  been  taken 
jis  evidence  that  they  are  composed  of  amyloid  material  (see  >j  ♦)."{).  It 
jniay  be  proved,  both  in  the  case  of  prostatic  concretions  and  of  renal 
olloid,  that  they  represent  cell-material  Mhicli  has  become  changed  into 
liyaline  substance.  In  the  case  of  renal  colloid,  liowever,  it  is  only 
mder  especial  conditions  that  the  particii)ation  in  its  formation  of  albu- 
nin  derived  from  the  glomeruli  may  l)e  excluded. 


•li  i^ 


.lif.l 


Colloid  is  il  collective  term 

ossoss  only  ccrtuiu  ])liysical  altri 
pinion  among  aiitliorsas  to  tiic  ; 
'or  example,  fon  J!,r/,-/i/,;///<ii/.'<r/i. 
ncludinj?  under  the  last'-nanwd 
•onnective  tissue,  as  well  as  hyaline 
hdiid  gives  tlie  term  a  more'limite 

I'orms  of  ei)ithe]ial  mucin-formation  (i)articuiarly  in  tumors),  and  also  hya'Mie  forma 
.ions  in  coimective  tissue,  biasmneli  as  eolloid  is  not  a  dcfinit(M'hemical  entity,  and 
U  its  staining-reactions  do  not  differentiate  it  sharply  from  other  hyaline  suhstances.  it 
eems  to  me  most  e.xpedient  to  apply  the  term  only  to  those  Jiyaline  i)ro(nicts  of  epitliu- 


to  a  great  variety  of  formal  inns  liial 
iinon.  Tliere  is  a  very  great  dill'erentc  of 
ppiicalidii  of  the  term.  Vnder  colloid  degeneration, 
jiiaccs  mucous,  amyloid,  and  hyaline  degenerations: 
■pithclial  colloid-formation,  hyaline  degencraiion  of 
igulation-nccroscs  and  hyaline  thrombi.  .]/<ir- 
ipldicatioii,  hut  inchidcs  under  (olloid  certain 


212  THE    RETROGRADE    CHANGES, 

lium  which  do  not  possess  the  characteristics  of  mucin.  I  liave,  therefore,  also  classified  ■ 
as  colloid  those  epithelial  concretions  which  on  account  of  their  reaction  with  iodine ; 
(brown  or  blue  color  when  treated  with  dilute  iodine  solutions)  have  hitherto  been  re-^ 
garded  asam3'loid  bodies,  if  objection  is  made  to  the  classification  of  these  formations;] 
as  colloid,  they  may  be  placed  under  the  heading  of  epithelial  hyalin. 

As  epithelial  hyalin  (l^eratohj^alin?)  may  be  classed  also  the  /ii/( dine  c/raniiles  and\ 
spliemdes  described  hy  JiuHsel,  Klein,  and  others,  and  which  are  found  especially  in  can-ii 
cer  cells.  They  stain  intensely  with  fuchsin,  and  also  with  Gram's  method  or  with; 
Weigert's  fibrin  stain.  It  should  be  noted  further  that  similar  bodies  of  varying  size  ■ 
and  form  have  been  observed  in  the  epithelium  during  the  development  of  a  vaccination ; 
pustule  (Iliickel),  and  have  been  by  many  regarded  as  parasites. 

Literature.  | 

(CoUoid.)  ' 

Biondi:  Beitr.  z.  Structur  u.  Function  d.  Schilddruse.     Berl.  klin.  "Woch.,  1888.  ] 

Bozzi:  Untersuch.  Liber  die  Schilddriise.     Beitr.  v.  Ziegler,  xviii.,  1895. 

Bubnow:  Chemische  Bestandtheile  der  Schilddriise.     Zeitschr.  f.  pins.  Chem.,  viii.,; 

is.s;^.  *  I 

Ernst:   Ceber  Hyalin  u.  seine  Bezieh.  z.  Kolloid.     Virch.  Arch.,  130  Bd.,  1892.  ' 

Hlickel:  Die  Vaccinekorperchen.     Beitr.  v.  Ziegler,  Supplh.,  1898.  j 

Hiirthle:  Secretionsvorgjiuge  in  d.  Schilddruse.     Pfliig.  Arch.  f.  d.  ges.  Phvs.,  5G  Bd.,' 

1804. 
Klien:  Russelsehe  Fuchsinkorperchen,     Beitr.  v.  Ziegler,  xi.,  1892. 
Langendorf:  Beitr.  z.  Keuntn.  d.  Schilddriise.     Arch.  f.  An.,  Supplh.,  1889. 
Marchand:  Koiloidentartuug.     Eulenburg's  Realencyklop.,  1895. 
Pianese:  Ilistol.  u.  Aetinl.  d.  Carcinoms.     Beitr.  v.  Ziegler,  Supplh.,  1896. 
Podbelsky:  Kolldid  in  den  Lvmphgef.  d.  Schilddriise.     Prager  med.  Woch.,  1892. 
Pratt:  Goitre.     Kef.  Handl).  ^f  Med.  Sc,  1902. 

V.  Recklinghausen:  Allg.  Pathol,  des  Kreislaufs  u.  der  Erniihrung,  Stuttgart,  1883. | 
Reinbach:  Bildung  des  Kolloids  in  Strumen.     Beitr.  v.  Ziegler,  xvi..  1894.  j 

Russel:  Characteristic  Organism  of  Cancer.     Brit.  Med.  Journ.,  ii.,  1890.  i 

Virchow:  Die  krankh.  Geschwlilste,  iii.  Bd.,  mid  Ueber  d.  eigenthiiml.  Yerhaltcu  al' 

buminoser  Fliissigkeiten  bei  Ziisatz  von  Salzen.     Vi:'.  Arch.,  6  Bd.,  1854. 
Wolfler:  Der  Bau  des  Kropfes,  Berlin,  1883. 

X,  The  Pathological  Cornification  of  Epithelium. 

;jtjl.   The  cornification  of  the  surface  epithelium  over  the  eutir 
skin  i.s  ci  i)liysi()loj;ic;il  process,  characterized  esseutially  by  the  fact  tha: 
the  cells  in  the  outer  strata  of  the  prickle  layer  of  the  stratum  germinc\ 
licum  undergo  a  horny  change.     This  cornification  takes  place  first  aj 
tlie  periphery  of  the  cells  and  in  the  processes  binding  the  cells  togetheil 
while  at  the  same  time  the  inner  portions  of  the  cell  and  the  nuclei;| 
shrink,  so  that  the  cells  become  changed  into  thin,  flat,  horny  scaleit; 
Tliis  lK)rny  substance  or  T<eraUn  is  a  very  resistant  modified  albuminoiji 
body  of  homogeneous  composition,  and  is  capable  of  resisting  digestioite  i 
by  the  gasliic  or  itancrcatic  juices.  f 

As  ac<'omi)anying]»lieuomena  of  cornification  there  appear  in  the  eel 
of  the  prickU;  layer  pecidiar  hyaline  granules  and  spherules  resembliri 
colloid,  which  stain  intensely  with  nuclear  stains  and  are  known  as  A:m 
tohjialin  (W'aldeyer).  In  those  areas  of  the  skin  possessing  a  thick  horrj 
layer,  lher(!  is  formed  a  sharply  limited  layer  of  such  keratohyalin-co] 
laining  cells;  this  layer  is  known  as  the  sindum  gramdosum.  In  tho;| 
l>laces  wheic  the  horny  layer  is  thin,  the  stratum  granulosum  is  impei| 
lectly  developed  and  ('\iiii)its  bi'eaks  of  continuity. 

Pathological  cornification  may  occur,  in  the  first  place,  as  a  widj 
spread  or  localized  increase  of  the  horny  layer,  resulting  in  a  conditi(* 
oi  hi/prihojdi;/  nf  the  homy  layer  of  the  epidermis  (see  Chapter  YI.,  §  7( 


'^ 


J« 


COK.MFirATIOX.  213 

or  hifperlerotosis.  This  pluMionuMioii  may  Ix-  piiinaiy — that  is,  (h.<'  to 
intrinsic  causes  inherent  in  the  anlauc  of  tlic  skin  (ielilliyosis,  lichen 
pilaris) — or  may  be  acquired  as  the  result  ot'e\t«'rnal  inllucners,  mceliani- 
eal  lesions,  infections  and  intlaminations  (callosities,  corns).  Furtiiei, 
there  may  occur  disturbances  in  the  process  of  cornilicatiou  of  the  skin, 
so  tiiat  certain  pathological  uuinifestations  recoi;nizable  by  the  naked 
eye  may  make  their  ai)pearauce,  such  as  des<|uanuition  (►f  the  skin.  Sucli 
change:;  are  included  under  the  term  paraJicraioHrH.  They  occur  especially 
as  sequela?  or  concomitant  phenomena,  of  iid'ections  of  theepid«'rmis,  and 
of  iutiammations  of  the  coiium  and  papillaiy  body,  souu'times  \vith(»ut 
auy  recoii'iiizable  cause  ;  and  in  these  cases  either  the  ])rocess  of  corniliea- 
tiou  or  of  the  formatiou  of  keratohyalin,  or  both,  is  (listnrbed. 

Finally,  pathological  coniijicaiion  often  occuis  in  fCf/ioiis  ir/icrr  normdllji 
it  either  does  not  occur  at  all  or  but  to  a  slight  extent.  In  the  skin  tht;  coi-- 
nilication  may  extend  to  the  ducts  of  the  sebaceous  glands  and  to  the 
hair-follicles  (ichthyosis)  or  to  the  sweat-glands  (porokeratosis).  Fur- 
ther, pathological  coruificatiou  occurs  not  infrequently  in  the  mucous 
membrane  of  the  mouth,  giving  rise  to  white  tliickeuings  of  the  epithe- 
lium oi"  to  hair-like  formations  (hairy  tongue).  J b)iny  change  may  l)e 
observed  also  in  the  mucous  membrane  of  the  middle  eai-,  in  tlie  mastoid 
cells,  in  the  descending  urinary  passages,  and  in  these  i)laces  it  may  lead 
to  ^he  formation  of  shining  white  scales  (formation  of  chole.steatoniata). 

Cornification  of  cancer  cells  is  very  frequently  seen,  particularly  iu 
cancers  of  the  skin,  iu  which  the  horny  scales  are  found  usually  in  the 
form  of  round  masses  resembling  onions  or  pearls.  Similar  liorny  pi'od- 
ucts  are  also  found  in  cholesteatomata  of  the  pia  and  brain. 

The  pathological  formation  of  horny  substance  in  the  mucous  mem- 
branes or  in  tumors  takesplace  either  simply  through  cornilication  of  tlm 
j cell-membranes  with  contraction  of  the  cell,  or  it  may  be  condjined  with 
I  the  formation  of  keratohyalin  as  in  the  case  of  typical  cornification. 
jThe  formation  of  keratohyalin  and  the  cornification  of  epithelial  cells 
often  occur  irregularly  distril)uted,  particulaily  in  cancers. 

Literature. 

(Cornijication.) 

Best:  Vcrliornimg  dcs  Bimlehautopitliels.     Bcilr.  v.  Di-utscliinaiui,  -'A  II.,  1S98. 

Bostrom:  Piale  Epidcnnoidc.     Cbl.  f.  allg.  Path.,  viii.,  1S<J7. 

Brosin:  Die  sclnvarze  Ilaarzunge,  Leipzig,  1888. 

Denoir:  Dc  la  langue  noire,  Paris,  1878. 

Dinkier:  Scliwarze  Haarzunge.     Yirch.  Arcli.,  118  Bd.,  1S8S. 

Ernst:  Hezieh.    d.   Keratohvalins  zum  Hvalin.     Vireii.  Anli.,    i:5n  I'.d..    is!)\!  (bit.); 

Nonnale  Verhornuug.     Arch.   f.  iiiikr."  Aiuit.,  47  Bd.,  ls!Mi ;  i':illi..l.    V.rlionnuig. 

Ik-itr.  V.  Ziegler,  .\.\i.,  1897  (Lit.). 
'Haug:  Das  Clio'iesteatom  d.  Mittdohrraunie.     Cbl.  f.  allg.  Patli.,  vi.,  Is!).".. 
Joseph:  P()rf)k(ratosis.     Arch.  f.  Derm.,  Si)  Bd.,  1S97. 
Leloir:   bcuknidakic  Imrcale.     Arcii.  de  phvs.,  .\..  1887. 
Mertsching:  Iv-ratolivaliii  n.  Piirinent.     Vircli.  Arch.,  110  Bd.,  1SS!». 
Nehrkorn:  .M<niniria]"c  I'crlgesclnvulst.     Beitr.  v.  Ziegler,  .\.\i.,  ls!)7. 
Posner:  Scldciinhaul  vcriioriiung.      Virch.  Arcii.,  lis  Bit,  issy. 
CJnna:  Haiidh.   d     Ilautkranklieiten,   Leipziir.    18H:5;    Die  Histopath.-lo-je  drr  ITaiit- 

krankheiten,  Berlin,  1894;  Wesen  der  Verhonuing.     Mlincli.  nied.  Wncii.,  l^HC. 
Wassmuth:  Hyperkeratosis  difTiisa.     B.itr.  v.  ZiegU-r,  x.wi.,  189!(. 


214  THE    RETROGRADE    CHANGES. 


XI.  Amyloid  Degeneration  and  thie  Amyloid  Concretions. 

§  G2.    Amyloid  degeneration  is  a  peculiar  degeneration  of  the  con» 

necitive  tissue  i>f  the  blood=vessels,  characterized  by  a  deposit  of  an 
alhaiiiiiioid  suhstanre  ((ninfioid)  in  the  affected  part,  so  that  the  tissue  iii- 
civases  in  mass  and  at  the  same  time  acquires  a  peculiar,  f/Jassy,  homof/e- 
neoiis  ap])earanc€.  The  degeneration  may  occur  in  almost  all  the  organs 
of  the  body;  but  is  especially  frequent  in  the  spleen,  liver,  kidneys,  in- 
testine, stomach,  adrenals,  i)ancreas,  and  the  lymph-glands.  It  is  moif 
rarely  observed  in  adipose  tissue,  thyroid  gland,  aorta,  heart,  musclts, 
ovaries,  uterus,  and  in  the  urinary  passages. 

Extensive  deposits  of  amyloid  may  be  recognized  by  the  naked  eye, 
as  the  affected  parts  x>i"esent  a  translucent  appearance  resembling  bacou 
{Janlaceous  deyenemiion). 

In  the  Hxdecn  the  change  occurs  most  frequently  in  the  follicles,  which 
in  a  certain  stage  of  the  degeneration  may  become  converted  into  homo- 
geneous, ti'anslucent  bodies  (Fig.  SQ,  h)  resembling  grains  of  boiled  sago, 
wherefore  this  form  of  amyloid  spleen  is  known  as  sago  spleen.  When 
the  amyloid  change  occurs  throughout  the  spleen-pulp  it  may  be  recog- 
nized on  the  cut  surface  of  the  organ  as  more  or  less  distinct  spots  or  I 
streaks.  ITltimately  the  greater  part  of  the  substance  of  the  spleen  may' 
become  affected.     The  spleen  is  thus  enlarged,  its  consistency  becomes.' 


^^^ 


wm 


y-  si,^;^Vvv;.  f ;'  •'■  .  '■;■';  '.  \i'^^^^^^0^^'i^^'i^W^^^^^^^^ 


Fh;.  8f).— Amvldiil  <lc!ri-ni'i;iti(in  fif  tlie  splenic,  follirlcs  and  neighboring  tissue.  (Muller's  — , 
haemato.xylin,  and  cnsin.)  (/.  Tinnsvcrsc  section  (if  splenic  arterv;  /»,  amyloid  areas;  c,  pulp;  (7,  f 
I'wnla?.    ; ;  :>(). 

v<My  hard,  and  the  organ  under  certain  conditions  may  be  complete 
transformed  into  a  bacon-like  substance  (lardaceous  spleen). 

The  lirer,  in  cases  of  well-marked  amyloid  degeneration,  is  increasl 
ill  size  and  of  ai  firmer  consistency.  On  section,  the  liver-tissue  is  foui 
to  be  leplaced  to  a  greater  or  less  extent  by  translucent,  lardaceco 
inasses,  between  which  the  remains  of  the  liver-tissue  appear  as  brov  ■ 
ish  or  yellowish  (from  abundance  of  contained  fat)  areas. 


< 


AMYLOID. 


21i» 


The  lidney,  in  cases  of  extensive  amyloid  cliauge,  is  likewise  enlaijietl 
and  liaideued,  aud  on  section  shows  hyaline,  lardaceons  si)ots  andslieak> 
of  lirm  consistency.  3Ioie  freqnently  there  is  found  a  white,  fatty, 
swollen,  Of  normal-sized  kidney,  in  which  only  here  and  there  may  1»<' 
seen  small  hyaline  .urannles  or  streaks,  or  the  presence  of  amyloid  may 
be  recognized  oidy  after  the  tissues  have  l)een  tr«'ated  with  iodine. 

In  the  intestine  and  lymph-.ulands  the  dci;* 


ration  iisuallv  cann< 


-Section  from  an  amyloid  liver,  treated  with  iodine  solution. 


be  lecognized  without  the  aid  of  the  microscope  and  chemical  reagents; 
aud  the  same  thing  is  true  in  regard  to  the  other  organs  which  are  moir 
rarely  affected,  such  as  adipose  tissue,  heart-muscle,  the  great  Idoud- 
vessels,  the  thyroid  gland,  etc. 

The  substance  which  is  deposited  in  amyloid  degeneration  foinis 
chietiy  shining,  homogeneous  masses,  which  exhibit  a  eluudcteristic  n- 
action  u'dit  iodiur  a.s  irrJl  as  irifJi  ra  lions  aniline  di/cs.  /r>^//»r  dissolved  in 
water,  or  better  in  a  solution  of  potassium  iodide,  and  ptaired  o\-er  the 
affected  tissue,  stains  the  amyloid  substance  a  dfolc  brownish- nd  (  malmg- 
any  l)r<twn).  In  thin  sections,  under  the  microscope,  the  amyloid  a  i)peai>: 
a  bright  hroirn-rfd  (Fig.  87,  b)  while  the  remaining  tissue  is  of  a  straw- 
yellow  color  (aj. 

lu  marked  amyloid  degeneration,  when  the  tissues  ai-c  of  a  \vo(i<lcn 
hardness,  the  iodine  reaction  sometimes  gixcs  a  blur  ov  f/rrm  co/or.  Pre- 
parations Avhich  ha\e  been  changed  to  a  mahogany  brown  ihrougli  tli<- 
action  of  iodine  become  still  deepei-  brown  when  treated  wilh  (bhile  sul- 
phuric acid  or  with  a  solution  of  zinc,  chloride,  or  tliey  may  become 
bright  red,  violet,  blue,  or  green.  This  rea<-tion  is,  however,  imperfert 
in  the  majority  of  cases. 

Metlij/l  violet  stains  amyloid  a  rub//  red  (Fig.  8S,  a,  b),  while  the  nor- 
mal tissue  takes  a  blue  or  dark  blue- violet. 

Because  of  the  peculiar  reaction  with  iodine,  A'irchow  was  1<'(1  to  le- 


216  THE    RETROGRADE    CHANGES. 

gard  the  amyloid  substance  as  a  noii-nitrogeuoiis  body  closely  related  to 
cellulose  or  starch,  inasmuch  as  cellulose  when  treated  with'  iodine  and 
concentrated  sulphuric  acid  becomes  bright  blue,  and  starch  similarly 
treated  gives  an  ultramarine  color.  Virchow  accordingly  gave  the  name 
amyloid  to  the  newly  discovered  substance.  Several  years  later  Fried- 
reich and  Kekule  showed  that  amyloid  is  a  nitrogenous  body  of  an  albi; 
minous  nature.  According  to  the  investigations  of  Krawkow  amyloid 
is  a  firm  combination  of  chondroitin-sulphuric  acid  Avith  an  albnmin. 

The  peculiar  reactions  of  amyloid  enable  us  to  detect  its  presence  in 
the  tissues  when  it  is  present  in  such  small  amounts  as  to  be  otherwise 
practically  invisible.  In  the  microscopic  examination  of  fresh  prepara- 
tions care  should  be  taken  to  wash  out  the  blood  from  the  piece  of  tissue. 
since  the  color  resulting  from  the  combination  of  the  blood  and  the  iodine 
may  be  deceptive. 

Amyloid  is  very  resistant  to  acids  and  alkalies.  Alcohol  and  chromic 
acid  do  not  affect  it;  and  it  is  also  very  resistant  to  putrefactive  changes. 


.  88. — Amyloid  degeneration  of  the  splenic  follicles  and  pulp.    (Alcohol,  methyl  violet,  hydrochloiic 
icid.)    a.  Follicle  showing  marked  degeneration ;  b,  pulp  showing  beginning  degeneration.    X  300. 


Fic: 
acid.) 


Amyloid  is  deposited  in  the  grontul-suhstance  of  the  connective  tissue  of 
the  blood-vessels,  cspcciaJJij  in  the  walls  of  the  smaU  vessels.  Living  cells  are 
not  affected.  In  the  connective  tissue  the  amyloid  substance  appears 
first  between  the  fibrilhe. 

In  the  acini  of  the  liver  the  amyloid  is  found  along  the  capillaries. 
The  endothelium  (Fig.  89,  c)  is  covered  on  its  outer  side  by  a  thick  layer 
of  a  homogeneous,  glassy  substance,  which  in  part  may  be  broken  up 
through  numerous  clefts  into  lumpy  masses  (c)  of  amyloid  material. 
The  liver-cells  between  the  amyloid  masses  are  either  intact  (a)  or  com- 
liressed  (/>),  or  already  atrophic,  or  may  have  wholly  disappeared. 
They  very  often  contain  fat.  The  afferent  blood-vessels  of  the  liver, 
l)articulaily  tlie  media  of  the  arteries,  may  also  show  amyloid  deposits. 

In  the  kidneys  (Fig.  90)  the  amyloid  is  found  particularly  in  the 
vessel-walls.  The  cajnllaries  of  the'glomeruli  (l>)  may  be  greatly  thick- 
ened and  homogeneous;  likewise  the  arteries  (/),  the  veins,  and  the 
capillaries  (A)  of  other  parts  of  the  renal  parenchyma  may  show  amyloid 


I 


AMYLOID. 


till'  (U'posit  is  also  found  i)arl  iciilaily 


deposits.      Ill  the  iiiU'stiiial  iiau 
in  the  "walls  of  the  blood-vessels. 

Ill  fat-tissue,  whieh  is  oeeasionally  extensively  involved,  the 
substance  is  found  partly  iu  tiie  vessel-walls,  and  ])artly  in  the 
live  tissue,  and  the  membranous  sheath  of  the  fat-eells  inay  be 
converted  into  a  hyaline  mass.  In  the  spleen  the  connect iVe-ti^ 
hecula)  (Fig.  88,  a,  h)  and  the  vessel- walls  are  especially  like 
att'ected,  and  may  suffer  a.  marked  thickeniiii;  (/>).  In  striped 
the  iHMimysium  internum  and  the  sarcolemnui  are  involved.  In 
lar  organs  possessing  a  tunica  propria,   as,   for  exami)le,   the 


am>lnid 
conui'c- 
entirely 
isue  tra- 
ly  to  be 
mrisele 
glandu- 
mueons 


Fig.  89.— Amyloid  degeneration  of  the  liver.     (Alcohol,  Van  Gieson's.)    a.  T.iver-cells,  in  part  containing 
fat:  //,  compressed  liver-cells;  c,  amyloid.     :•:  ~MK 


lijlauds  and  the  kidneys,  this  membiant^  may  become  affected  and  greatly 
Ithickened. 

The  results  of  amyloid  degeneration  upon  the  functions  and  \  itality 
|)f  the  affected  organ  are  shown,  through  anatomical  investigation, 
'most  prominently  in  the  marked  chaiu/e  of  structure  on  the  one  hand,  and 
;)U  the  other  hand  in  the  associated  dcf/encration  and  tlu^  di.sdjtptdrdncr  of 
'he  cdhdar  c/ciiicnts.  Amyloid  disease  is  eminently  degeneiative  in 
ji-haractc)-.  The  connective  tissue  itself  is  permanently  changeil,  as  the 
Practically  insoluljle  amyloid  is  ne\er  remo\ed  from  it. 
I  The  deposit  of  amyloid  substance  in  the  tissues  of  the  blood-vessels 
•  eads  to  a  very  maiked  thickening  of  their  walls,  and  to  n  narrowing  or 
jr-ven  obliteration  of  their  lumina  (Fig.  00,  h),  and  in  this  way  to  a  i)er- 
.iiaueut  disturbance  of  circulation.  The  amyloid  masses  may  compress 
neighboring  epithelial  structures  (Fig.  8<))  and  causti  them  to  atrophy. 
)ften  there  is  associated  a  fatty  degeneration  of  the  epithelium  (Fig.  00, 
,  /■),  paiticularly  in  the  kidneys;  but  this  change  is  not  to  be  leferred 
vholly  to  the  disturbances  of  ciiculatiou  caused  by  the  amyloid  deposit, 
t  is  more  likely  that  the  fatty  degeneiation,  at  least  in  ])ail,  is  ;i  path- 
|)logical  process  running  paiallel  m  ith  the  amyloid  disease,  and  caused 
|)y  the  same  conditions  x>i"oducing  the  lattei'.     ('onse(|neiitly,    m   sonn^ 


218  THE    RETROGRADE    CHANGES. 

cases  the  amyloid  change  may  be  slight,  while  the  fatty  degeneration  i{ 
very  marked. 

lu  the  spleen  and  lymph-glands  the  lymphoid  cells  lying  in  tb< 
meshes  of  the  thickened  reticulum  (Fig.  88,  a)  disappear  as  the  result  oJ 
atrophy  and  fatty  degeneration.  In  muscles  the  contractile  substance 
diminishes  in  proportion  to  the  increase  of  the  amyloid  deposit  in  con 
uective  tissue. 

Amyloid  deposit  is  usually  a  sequela  of  cachexia  due  to  chronic  ulcer 
(dive  tuherculo.siH  of  different  organs,  chronic  suppuration  (for  example,  o 
the  bones),  syphilis,  or  chronic  dysentery.  In  the  cachexia  of  carcinomj 
it  is  but  rarely  observed.  In  rare  cases  the  degeneration  occurs  withonl 
being  associated  with  any  of  the  above-mentioned  diseases. 

xVccording  to  investigations  by  Czerny,  Ivi'awkoAV,  Lubarsch,  David 
solin,  Maximow,  Xowak,  Petroue,  and  h?chepilewsky  amyloid  may  b( 
jjroduced  experimentally  in  the  spleen,  liver,  kidneys,  and  intestines  ot 
various  animals,  rabbits,  chickens,  do\'es,  mice,  and  dogs,  through  the 


€ 


■Pio.  9a— Section  of  an  amyloid  kidnev.  (Miiller's  fluid,  osmic  acid,  methyl  violet.)  fl.  Normal  vasruv 
lar  loops;  7,,  amvloid  vascular  loops  ;  c,  fatfv  crloiniTiiliir  cpitlu'limn  :  <•,,  fatty  capsular  epitlieliuui ;  ((,  iBt( 
drops  IviiiLf  aLMi'nst  Ilic  outiT  suifiicr  of  tin'  capilhirv  walls:  i.  fattv  .■pithelium  ui  si'tu;  /,  desfiuamata 
and  fallv  f|iiiheliiuii :  (/,  livaliiic  cMauiila  least  );  ]\.  iraiisMMs;.  scciinn  (if  a  cast  composed  of  fat-drops:  i 
ainvIoidarttTv;  /,.  amyloid  capillai\  ;  f,  ri'llular  inliltratiuii  of  thr  romicctivc  tissue;  m,  round  cells  withll, 
the  tiilMiles.     A  'im.  i 

\ 

production  of  suppurations  lasting  several  weeks.  Amyloid  may  de^i 
velop  also  in  horses  that  are  inoculated  with  diphtheria  bacilli.  Suppuraj 
five  processes  caused  by  staphylococci  and  oil  of  turpentine  api)ear  iii 
])ail  icular  to  favor  the  foi-mation  of  amyloid.  In  a  number  of  cases  amy 
loid  was  also  successfully  produced  through  injections  of  decomposcc 
bouillon,  dead  cultures  of  stai)hylococci,  rennet -ferment,  and  pancreatii, 
(SciiepiU'wsky  ),  when  the  inllammation  produced  l)y  these  agencies  rai||ni^^ 


•luewhat  chi-onic  coni-se.  Krawkow  observed  the  beginning  of  amy-j 
loid  formation  after  three  days,  K"ow"ak  after  eight  dajs.  i 

riie  orifiiii  of  the  amyloid  substance  has  not  yet  been  definitely  deter-^ 
mined.  Tlie  results  of  experimental  investigation  vary  greatly,  the  de, 
generation  being  often  absent  in  cases  of  chronic  suppuration  (particu-i 


'W 
Sale:: 


AMYLOID.  210 

larly  in  dogs).  II  is  pi-obablc  that  llic  blood  l)i-iiins  to  Uie  tissues  some 
substance  ^vhi(*h  is  diaiiiied  into  amyloid  at  the  site  of  deposit.  It  has 
been  many  times  sliown  that  as  the  ((iitcccdcnf  of  umyJoid  there  is  found 
aliiiolhic  siibxi((ii('c  \\\  \\\v  tissues,  Avliieh  does  m)t  give  the  amyloid  reac- 
tions. Similar  obser\  at  ions  luive  occasionally  l)een  made  in  man.  Tip' 
material  fi'om  Mliich  am>  loid  aiises  is  foj'mcd,  ]>("rliai)s,  by  (lisintcgiat ing 
pus-cells  or  tissue-cells  at  the  scat  of  the  primaiy  disease  and  thence 
enters  the  blood-stream. 

According  to  Krnirh<>(r.  lliere  are  found  normally  in  the  wall  of  \\\v  horse's  aorta,  in 
the  liganientuni  nnelia'  of  cattle,  in  the  stroma  of  the  spleen  of  ealves,  and  in  the  mu- 
cous membrane  of  the  stomach,  combinations  of  clioiulroitin-sulphuric  acid  wliicli  are 
closely  related  to  amyloid.  According  to  Ncubcrg,  amyloid  proper  is  a  basic  albumin  in 
the  process  of  mctamorjihosis  comliined  witli  chondroitin-sidjihuric  acid.  From  this 
last-named  combination  the  basic  albumin  body  may  l)e  easily  ditrerentiati'd  cliemically. 

Literature. 

(Aini/h>id.) 

Abraham:  Ueber  eiirenthiindiche  Formen  ainyloider  Entartuim-.  biaug.-Diss.,  Frei- 
burg. 1891.  "  ■     ' 

Browicz:  llerkiinft  d.  Amylsubstauz.     Bull,  de  I'ac.  des  sc.  d.  Cracovie,  1901. 

Burchardt:  Amyloidfarbuug  (Gentianaviolett,  Sal/siiure).    Virch.  Arch..  117  Bd.,  1889. 

Czerny:  Zur  Kenntn.  d.  glykogenen  u.  amyloidcn  Entartung.  Arch.  f.  e.xp.  Path., 
:!1  r.d.,  1893. 

Davidsohn:  Exper.  Erzeugung  von  Amyloid.  Virch.  Arch.,  150  Bd.,  1897;  Erken- 
nuui:  /wrier  ^^ladien  der  Amvloidentartuni:.     Ibid.,  ir^'t  Bd.,  1899. 

Eberth:  Die  amyloide  Entartung.     Virch.  Arch.,  80  Bd.,  1880. 

Edens:  Histopatliologie  lok.  u.  allg.  Amyloiddegeueratiou.    B.  v.  Ziegler,  xxxv.,  1904. 

Friedreich  u.  Kekule:  Zur  Amyloidfrage.     Virch.  Arch.,  1(5  Bd.,  1859. 

Grandis  ct  Carbonne:  Reaction  de  la  substance  amyloide.     Arch.  ital.  de  IiioL,  xiv., 

IN'.M. 

Grigorieflf:  Resorptionsfahigkeit  d.  Amyloids.     Beitr.  v.  Ziegler,  xviii.,  1895. 

Henning-s:  Zur  Statistik  u.  Aetiologie  der  amvloiden  Entartung.  Inaug.-Diss.,  Ber- 
lin, ISSO. 

Hjelman:  Studier  ofver  Amvloidin  jurens.  Inaui;-.-Diss.,  Ilelsingfors,  ref.  C'bl.  f. 
allg.  Path.,  ii.,  1891. 

Jiirgens:  Eine  neue  Reaction  auf  Amyloidkorper.     Virch.  Arch.,  65  Bd.,  1375. 

Krawkow:  Exper.  Erzeug.  v.  Amyloid.  Cbl.  f.  allg.  Path.,  1895;  Arch,  de  med. 
ex]..,  1S96;  Chemie  der  Amyloidsubstanz.     Arch.  f.  exp.  Path.,  40  Bd.,  1897. 

Kiihne  u.  Rudnew:  Zur  Chemie  der  amvloiden  Entartung.  Vircli.  Arch.,  o'3  Bd., 
is(i5. 

Kyber:  Die  amyloide  Degeneration,  Dorpat,  1871;  Virch.  Arch.,  81  Bd.,  1880. 

Levene:  ((Jhoudroidin-sulphuric  Acid),  Med.  Rec,    1900. 

Lindemann :  Jodsch wefelsaure reaction  u.  Amyloid  (Krvstalle).  C'bl.  f.  allg.  Path., 
isilT. 

Lubarsch:  Exper.  Er/eugung  vou  Amyloid.  Virch.  Arch.,  150  Bd.,  1897;  Il^'aline 
u.  amyloide  Degcn.     Ergebn.  d.  allg.  Path.,  iv.,  Wiesbaden,  1899. 

Maximow :   Experimentell    hervorger.    Amvloidentartung.      Virch.   Arch.,    153  Bd., 

IN'.IS. 

Neuberg:  Amyloidentartung.    Verb.  d.  D.  path.  Ges..  vii.,  .Tena,  1904. 

Neumann:  Ueber  Amyloiddegeneration  des  Fettge\vel)cs.     ('enfrall)l.    1.   aliu'.    F^illi., 

i..  1890. 
Nowak:  Aetiologie  der  Amyloidosis.     Virch.  Anh.,  152  15(1..  1898. 
Petrone:   Degrn.'amyloide  experimentalc.     Areli.  de  med.  exp.,  1898. 
iRabe:   Aiiivlnidentartung  bei  Thieren.     .laiireslier.   d.   K.    Thierarzneischule    /.     Ifan- 

nnver.  'ivv;; -,S4. 
Schepilewsky :   Kxpcr.  Erzeugimg  iimyloider  Degeneration.    Cbl.  f.  Bakt.,  xxv.,  1899. 
Schmidt:  Amvloidenlartung.  "  Verb.  d.  1).  path.  Ges. ,  vii.,  .leiia,  1904. 
vonSchrdtter":('lieniied.  Amyloiddeg.  in  Ott.  Ciiem.  Path.  d.  Tubercuhwe,  Berlin.  1903. 
Tarchetti:  Exper.  Amyloidentartung.     D.  A.  f.  kliii.   Med.,  75  Bd.,   1903. 
Tschermak:  t^tellung  d.  amyloid,  ttubst.     Zeitschr.  f.  phys.  Chem.,  xx.,  1875. 
Virchow:  Ueber  eine  iin  Geiiirn  und  liiickenmark  des  .Menschen  aufgefundeue  Sub- 

^taii/.  mit  der  chemi.schen  Reaction  der  Cellulose.     Vir.  Arch.,  6  Bd.,  1854. 
Wichmann:  Die   Amyloidentartung.     Beitr.  v.  Ziegler,  xiii.,  1893. 
Ziegler:  Amyloide  Tuniorbildung  in  der  Ziinge  und  im  Kehlkopf.     Virch.  Arch     G5 

Bd.,  1S75. 


220 


THE   RETROGRADE    CHANGES. 


§  6.3.  Tlie  form  of  amyloid  degeneration  jnst  considered  is  a  disease, 
which  usually  appears  as'  a  multiple  affection  of  several  organs,  or,  if 
confined  to  a  single  organ,  appears  as  a  diffuse  change  extending  through- 
out the  whole  organ.  There  is,  however,  a  localized  form  of  amyloid 
deposit,  appearing  either  as  a  local  amyloid  infiltration  of  the  tissues  or  in  the 
form  of  free  eoneretions. 

The  local  amyloid  infiltrations  occur  in  part  in  very  cellular  granu- 
lations (conjunctiva)  and  in  tissues  showing  chronic  inflammatory  proc- 
esses; and  iu  part  in  scars  and  in  hyperplastic  proliferations  of  connec- 
tive tissue.  They  are  also  found  occasionally  in  tumors  in  which  other 
retrograde  changes  have  begun.  In  certain  cases  only  small  deposits  are 
found  iu  the  affected  tissues,  usually  in  the  vessel-walls.  In  other  cases 
larger  nodules  consisting  almost  wholly  of  amyloid  may  be  formed,  and 
these  may  acquire  a  wooden  hardness. 

Here  also  the  amyloid  substance  is  deposited  in  the  f/round-suhsfance  of  the 
tissue;  but  it  has  been  claimed  by  some  authors  (Rahlmann)  that  the  cells 
of  the  tissue  may  acquire  a  hyaline  appearance  and  give  the  amyloid 
reactions. 

Such  local  formations  of  amyloid  have  been  found  in  the  inflamed 
conjunctiva,  in  syphilitic  scars  of  the  liver,  tongue,  and  larynx,  in  in- 
flamed lymph-glands,  in  the  urinary  bladder,  ulcers  of  the  leg,  and  in 
tumors  of  the  larynx  and  stomach.  Tumor=like  nodules  of  amyloid  also 
occur  in  the  conjunctiva,  tongue,  larynx,  lymph-glands,  and  trachea 
under  conditions  in  which  it  is  impossible  to  establish  any  relationship 
between  them  and  inflammatory  processes,  and  where  besides  the  hyaline 
masses  there  is  but  little  normal  connective  tissue  present.  According 
to  Burow,  Manasse,  von  Schrotter,  Zahn,  and  others,  such  nodules  may 
arise  also  from  connective-tissue  tumors. 

Free  amyloid  concretions  or  corpora  amylacea  occur  most  frequently 
in  the  tissues  of  the  central  ner^■(JUS  system,  especially  in  the  substance 
of  the  spinal  coi-d,  and  in  the  epeudyma  of  the  ventricle.     They  are 

found  also  in  the  prostate.  In  the 
ner\'ous  system  they  appear  as 
small  (Fig.  91,  c),  dull-shining, 
mostly  homogeneous  bodies,  more 
rarely  consisting  of  a  nucleus  and 
an  outer  shell  (Eedlich)  ;  in  the 
prostate  they  form  larger  (Fig.  91, 
a)  bodies  which  usually  show  a  dis- 
linct  stratification.  Corpora  amy- 
lacea have  also  been  found  in  car- 
cinomata  (Wagner,  Langhans),  and 
have  been  repeatedly  observed  in 
the  lung,  where  they  occur  in  in- 
flammatory areas,  htemorrhagic 
extravasations  (b),  and  in  em- 
physema. 

The  local  deposits  of  amyloid  and 
the  free  amyloid,  concretions  cannot  be 
regarded  as  being  ivholly  of  the  same 
nature  as  the  progressive  amyloid  de- 
generation of  connect  ire  tissue.  Some 
of  them  indeed  give  characteristic  amyloid  reactions,  and  the  cori)ora 
amylacea  of  the  nervous  system,  in  particular,  become  blue  or  brownish- 


© 


It  b 


¥ 
tatu    c  ()ti(  It  II 
from  .111  (ilil  1 
hariiatDiilin 
Corpora  aiiiyl 


I,  ('Mr|iiis 
1 111(11 '  h.itric  infiircl  cif  111' 
rsstils  111  Its  imrlciis. 
( ea  from  the  spinal  cord. 


" 


LOCAL    FOH.MATIOX    OF    A:\IYL0ID.  221 

violet  wIuMi  ti'oated  witli  iodine  and  snliihiiric  acid.  But,  in  the  case  of 
these  bodies,  we  have  to  do  with  loiiuations  whieh  are  dependent  essen- 
tially upon  local  conditions  lor  their  oi'igin;  and  which  are  derived  in 
part  from  ei)itheliuni,  and  in  part  from  connecti\('-tissue  cells.  They 
are,  therefore,  to  be  regaided  pai-tly  as  modihed  e])ithelial  liyalin  (§  ()0J, 
and  partly  as  modihed  connective-tissue  hyalin  (i^  ().")).  The  ])i'ostatic. 
concretions  aie  formed  throuji'h  the  fusion  of  masses  of  deiicnerat  iii<;'  v\n- 
thelial  cells  or  of  fra-nients  of  the  same  (ei»itlielial  colloid,  ^(i(»);  and 
the  similar  bodies  found  in  the  lun<;s  and  in  tumois  aie  comi)osed  essen 
tially  of  the  i)roducts  of  disintejiTated  cells,  thoujih  in  i)ai't  also  of  albu- 
min derived  from  the  blood.  The  corpoia  amylacea  of  the  nervous  sys- 
tem arise  i)robably  from  fragments  of  swollen  axis-cylinders  to  M'hich, 
perhaps,  remains  of  the  changed  medullary  sheath  still  cling. 

Literature. 

(Loral  Fonnaiion  of  Aniij^oid  aitd  Aiiiijfoid  ConcnA'ions.') 

Askanazy:  Lokale  Ainyloidbildung  in  d.  Darmmuskulatiir.     \qy\\.  il.  D.  j)ath.  Ges., 

vii.,  1904. 
Burk:  Aniyloidturaoren  d.  Thyreoidea  mit  Metastasen.     C.  f.  a.  P.,  xii.,  1901. 
Burow:    (Laiyn.xtumoren.)     v.  Langenbeck's  Archiv,  xviii.,  1867. 
Ceci:   ('(u-pusciili  amilacei  dell'  encefalo  e  midollo  spinale.     Atti  de   Lincei,  ix.,  ISSl. 
Eiger:   Zur  AiiiyloidtVage.     Cbl.  f.  allg.  Path.,  xi.,  1900. 

Friedreich:   Coipma  amylacea  in  den  Liingen.     Virch.  Arch.,  9,  10  Bd.,  1856. 
Fumag-alli  e  Krach.  :  Degen.  amiloide  della  congiuntiva.     Arch,  per  le  So.  Med.,  xix., 

1S9.>. 
Glockner:    Tuiuorfijrmiges  Amyloid  d.  Larynx.     Virch.  Arch..  160  Bd.,  1900. 
Grawitz :  ( Xase  und  Luftrohre  des  Pferdes.)     Virch.  Arch.,  94  Bd.,  1883. 
Herxheimer:   Amyloidtiimoren  d.  Kehlkopfes  u.  d.  Lunge.     V.  A.,  174  Bd.,  1903. 
Hildebrand:  C'orpora  amylacea  in  einem  endostalen  Sarkom.     Virch.  Arch.,  140  Bd., 

lS9r>. 
Hippel:   (Augcniid.)     Arch.  f.  Ophthalm.,  25  Bd. 

Hueter:   Aniyloidliihhmg  in  Kehlkopf.    Festschr.  f.  Orth,  Berlin,  1903. 
Johanni:   Annloidtumoren  d.  Kehlkopfes  u.  d.  Trachea.     A.  f.  Lar.,  xiv.,  1903. 
Kraus:  (Zunge,  Augcniid.  Trachea,  Leber.)     Zeitschr.  f.  Heilk.,  vi.,  1885;    vii.,  1886. 
Langhans:  Corpora  amylacea  der  Lunge.     Virch.  Arch.,  38  Bd.,  1867. 
Leber:    (Augenlid.)     Arch.  f.  Ophthalm.,  xix.  and  xxv. 

Manasse:  Tumorformiges  Amyloid  des  Larynx.     Virch.  Arch.,  159  Bd.,  1900. 
Posner:    Fcber  Prostataconcretionen.     Zeitsch.  f.  klin.  Med.,  16  Bd.,  1S89. 
Rahlmann:    (Augenlid.)     Arch.  f.  Augenheilk.,  x.;   Virch.  Arch..  87  Bd..  1SS2. 
Redlich:    Die  Aniyloidkorperchen  des  Nervensystems.     Jahrl).  f.  P.sj'ch.,  x..  1891. 
Rumschewitsch:    Hyaline  u.  amyloide  Entartung  d.  Bindehaut.     Arch.  f.  Augenli., 

2.-)  lid.,  ],S92. 
Saltikow:   Amyloidtumoren  der  Luftwege.     A.  f.  Lar.,  xiv.,  1903. 
Schmidt:   Amyloidtumoren  d.  Zunge.     Virch.  Arcli.,  143  Bd.,  1896. 
Siegert:    I'nters.  \\h.  d.  Corp.  amylacea.     Virch.  Arch.,  129  Bd.,  1892. 
Stilling:   Entstehung  von  Concrementen  der  Prostata.     Virch.  Arch.,  98  Bd.,  1884. 
Stratz:  Aniyl.  Degen.  e.  Cteru-spolypen.     Zeit.schr.  f.  Gebh.,  xvi.,  1889. 
Stroebe:   Picijarat.  Vorgiinge  bei  Heilung  von  Riickenmarkswunden.     Beitr.  v.  Zieg- 

ler.  XV.,   1S94. 
Tschistowitsch:  Amyloidtumoren  d.  Retroperitonealdriisen.    V.  A.,  17()  Bd.,  1904. 
Vossius:   .Viuyloide  Degeneration  der  Conjunctiva.     Beitr.  v.  Ziegler,  iv.,  1889. 
Zahn:  Corpora  amyloidea  der  Lunge.     Virch.  Arch.,  72  Bd..  1878. 
Ziegler:    Amyloide  Tumoren  der  Zunge  und  des  Kehlkopi's.     ^■ircll.  .Vrcli.,  ()5  Bd., 

1875. 


222 


THE   RETROGRADE    CHANGES. 


XII.  Hyaline    Degeneration    of   Connective  Tissue  and    the    Hyaline    ,   . 
Products  of  Connective=tissue  Cells. 


5  64.  Under  l.ie  head  of  hyaline  degeneration  of  connective  tissue 
juay  be  grouped  those  changes  in  Mhich  the  fibrous  f/roi(nd-.si(h.stanve  of  flir 
connective  tissue  of  the  hlood- vessels  acquires  a  hyaline  character  u-ithout  giving 
the  specific  reactions  of  amyloid  (Fig.  92),  The  change  may  involve  uoi - 
mal  connective  tissue  (Fig.  92),  or  that  altered  by  inflammation,  as  wt-ll 
as  the  newly  formed  connective  tissue  of  inflammatory  new-growths  and 
of  tumors.  It  is  dej)endent  partlj^  upon  local  and  partly  upon  general 
disturbances  of  circulation.  Hyaline  degeneration  is  found  most  often 
in  the  connective  tissue  of  the  thyroid  (Fig.  02,  h) ;  the  valvular  end(  »- 
cardium;  intima  of  the  arteries;  the  entire  wall  of  the  smaller  vessels, 
particularly  of  the  brain  and  spinal  cord ;  the  lymph-glands  (Fig.  94,  <^ 
h);  glomeruli  of  the  kidney;  the  connective  tissue  and  blood-vessels  of 
connective  tissue  tumors  of  the  dui-a  mater  (psammoma),  parotid,  and 
sabmaxillary  glands  (angiosarcoma) ;  the  connective  tissue  of  corneal 
scars;  the  peripheral  portions  of  tuberculous  nodules;  tlie  connective 
tissue  of  tuberculous  tendon-sheaths  and  bursiB  mucosie  (Fig.  9;>,  />). 

Hyaline  degeneration  of  connective  tissue  possesses  no  siiecific  staining  ' 
reactions,  as  does  amyloid.  Staining  with  Van  Gieson's  (acid  fuchsin ; 
and  picric  acid)  gi\es  to  liyaliu  in  the  great  majority  of  cases  an  intense 

fuchsin  red ;  but  this  re- ; 
f-rj      ~fc^       **2~"t  -a?** V"  -  ~  '"iiJWSiLri  action  is  sometimes  want- ; 

ing.  It  is  probable  that; 
the  degeneration  of  con- 
nective tissue  known  asj 
hyaline  represents  a  va- 
riety of  degenerati\e  con- 
ditions. Ey  many  autliors} 
hyaline  coagula  of  exu- 
dates, occurring  in  thel 
tissues,  are  included  \w\ 
this  group. 

In  many  cases  (thick 
ening  of  the  heart-valve.'! 
or  of  the  intima  of   ar 
teries)  the  tissue  appear(| 
on  microscopical  examin) 
ation    to    be    very   thicl' 
and  dense,  and  from  thi 
fact    the     condition    ha 
been  designated  sclerosis' 
The  cause  of  the  thicken' 
ing  and  homogenous  character  is  not  known.     The  gradual  disappearanc 
of  the  nuclei,  tlie  sid)sequent  calcification  (see  §  60),  or  softening  even  t 
the  point  of  complete  disintegration  (for  example  in  sclerotic  areas  o 
tlie  intima),  the  se(|uestiation  of  the  altered  tissue  from  the  normal  (fo 
exami»]e,  in  the  degenerated  portions  of  the  w^allsof  the  burste),  all  poir 
to  the  fad  that  the  process  is  essentially  degenerative  in  character. 

\n  other  cases  the  appearance  of  the  hyaline  tissue  resembles  closed 
that  of  amyloid  degeneration,  and  there  is  associated  with  the  hyalir] 


Fig.  92.— Hyaline  defeneration  of  tlie  connective  tissue  of  a 
colloid  Koitre.  (Alcohol,  Van  Gieson's.)  a.  Follicles  containing 
colloid:  /a  hyaline  connective  tis-sue;  c,  blood-vessel.    X  300. 


COXNECTIVK-TlSSi  E    1 1  YAl.lN. 


223 


•as('   of 


chaii,t;e  a  iiroiKMiiiccd  increase    o!'    Inilk.    ])ail  iciilailx'    so    in    I  hr 

hyaline  (U\uvneiatioii  of  (lie  small  vessels  of  Uic  eeiilral  nervous 

H'l  ome  ml  i,    and   the 

lyniph-iilaiuls  (Fij;'.    91; 

<t,  h),  iiioie  rarely  in  the 

hyaline  deiieneratien  of 

the  oonneeli\e  tissue  it- 
self.   Theieoeeur,  niore- 

(tvei-,thou<ili  -veiy  larely, 

eertain  foiius  of  hyaline 

dciieneration    involving 

iseveral  organs,  the  heart 

l(Fig.   95,    />,    e),    serous 

jiuonibi'anes,       intestinal 

Iwall,  ete.,  with  the  foi- 

liiialion  of  glassy  masses, 
hi  eh  in  part  give  the 

amyloid  reaction,  and  in 

part  do  not.     In  prolif- 

■rations  of  the  conjunctiva  there  have  been  frequently  ol)ser\ed  hyaline 

legenerations  of  the  reticular  ground-substance  M'ilh  nodular  thicken- 

!ugs  of  the  same;  and  these  changes  give  the  amyloid  reaction  only  in 
)art.  It  may  therefore  be  assumed  that  there  is  a  form  of  hyaline  de- 
feneration of  the  connective  tissue,  which  is  closely  related  to  amyloid, 
ind  may  l)ecome  changed  into  the  latter  (see  >;  (>2) ;  and  that  it   arises 


Fig.  93.— Hyaline  degeneiation  of  the  connective  tissue  of  the 
wall  of  a  tubereulous  bui-sa.  (Miiller's  fluid,  hivmatoxylin,  anil 
eosin.)  n,  Fibrous  connective  tissue ;  h^  hyaline  connective  tissue. 
X  40. 


6 


'IG.   34.— Hyaline  degeneration  of  the  blood-vessels  of   an  atrophic  axillary  lymph-gland.      (. 
carmine.)     a.  Hyaline  vessel  with  open  lumen  ;  7(,  obliterated  vessel.     X  'Ml 

Fig.  95.— Hyaline  degeneration  of  the  connective  tissue  of  the  myocardium.  (Alcolml,  ha-ma 
annine.)  a.  Normal  connective  tissue;  7j,  hyaline  connective  tissue ;  c,  hyaline  masses;  ((,  tra 
ection  of  normal  muscle-cells,  of  atrophic  (c).    X  :i50. 


Ilirongh  the  dei)Osit  of  a  hyaliiu 
|)robablv  derixed  from  the  blood. 


insoluble  all)uii 


bodv  which   h 


I  The  prepanitioii  shown  in  Fig.  95  was  taken  from  the'  heart  of  a  Nvoniaii  of  lifty- 
pve  years  of  age,  the  greater  part  of  the  heart-wall  i)ieseiiting  a  liyaliiie  degeneration. 
jn  both  endo-  and  pericardiiuii  tliere  Avere  numerous  hyaline  nodules  and  tiattened 
jiiasses.  The  muscle  tissue  was  in  part  degenerated,  as  shown  in  tlie  ligure.  Associ- 
;.ted  witli  tliis  condition  there  was  extensive  degeneration  of  tlie  blofxl-vessels,  ]iai- 
licularly  of  tlie  intestines,  tongue,  lungs,  Jieart,  and  urinary  bladder.  'I'lii;  peritoneum 
H'a.s  also  thickly  covered  with  hyaline  nodules.  The  fact'tliat  the  small  arcjis  and  the 
i>eriphery  of  the  larger  ones  gave  no  iodine-reaction,  whik;  tiie  central  portions  of  the 
irger  areas  did  so,  appears  to  i)oint  conclusively  to  a  close  relationsliij)  between  iiyaline 
legeneration  and  amjdoid.     A  similar  case  lias  been  described  by  Steinliaus. 


224  THE    RETROGRADE    CHANGES. 

Literature. 

{JTliaJUie  Begeneration  of  Connective  Tissue.') 

Alzheimer:  Kolloidcntiirtunir  des  Gehirns.     Arch.  f.  Psych.,  xxx.,  1898. 

Arndt:  Eutartung  (Ut  Iliiniicfiisse.     Virch.  Arch.,  41  Bd.,  1867.  ; 

Best :  Ucber  die  retrressi veil  Erii;iliniugsstorungeu  (hyaliue  Coucretioucn)  bei  baudformi-' 

ger  Hornhauttrubung,  Hamburg,  1900. 
Birch-Hirschfeld:  Dcgenerat.  Processe  in  Hornhautnarben.     Gracfe's  Arch.,  48  Bd., 

1899. 
Eppinger:    Ilvaline    Entartung   d.  Hiriigefiisse.     Vierteljahrsschr.   f.   prakt.  Ilcilk.. 

Prag,  187o. 
Ernst:  Hyalin  u.  seine  Beziehungen  zum  Kolloid.     Virch.  Arch.,  130  Bd.,  1892. 
Grawitz:'Amvl.  u.  hyal.  Neubildung  in  d.  Nasenschleinih.  e.  Pferdes.     Virch.  Arch.; 

94  Bd..  1883.  ' 

HolschewnikofiF:  Tlyal.  Degen.  der  Hirngefiisse.     Virch.  Arch.,  112  Bd.,  1888. 
Lubarsch:  Allxnniuijse  Degenerationen.  "Ergebn.  d.  allg.  Path.,  1895.  , 

Lubimoff:  Kolloiddegenerjition  d.  Hirngefasse.     Arch.  f.  Psych.,  iv.,  1874. 
Oeller:  Hyal.  Gefassdeg.  im  Auge  (Bleivergiftung).     Virch.  Arch.,  86  Bd.,  1881. 
Rahlmann :  Hyaline  u.  aniylnide  Deg.  d.  Conjunct.     Virch.  Arch.,  87  Bd.,  1882. 
Rumscliewitsch:  Amyl.  li.  hyaline  Degen.  d.  Bindehaut.    Arch.  f.  Augenlik.,  2; 

Bd  ,  1892.  j 

Steinhaus:  Hyalin-  u.  Amyloidinfiltration  im  Zirkulat.-  u.  Digestionsapp.      Z,  f.  Id; 

.M<m1.,  4.-)Bd.,  1902.  j 

Stilling-:  Amyloide  u.  hyaline  Degen.  d.  Milz.     Virch.  Arch.,  103  Bd.,  1886.  i 

Vossius:  Hj-aline  Degeneration  d.  Conjunctiva.     Beitr.  v.  Ziegler,  v.,  1889.  i 

Wieger:  Hyaline  Entartung  der  Lympiidrlisen.       Virch.  Arch.,  78  Bd.,  1879.  ; 

V.  Wild:  Amyloide  u.  hyal.  Degen.  d.  Bindegewebes.     Beitr.  v.  Ziegler,  i.,  1886. 
Ziegler:  Ursachen  d.  Nierenschrumpfung.     Deut.  Arch.  f.  klin.  Med.,  25  Bd.,  1878. 

§  65.  Hyaline  products  of  connective=tissue  cells  arise  iu  the  fii\'; 
place  from  spherical  masses  of  Jlat  connective-tissue  ceils  arranr/ed  in  coh, 
centric  iai/ers,  which,  in  a  mamier  similar  to  the  corniticatioii  of  ep:j 
thelial  cells,  become  chauged  into  a  hyaline  substance  containing  vo  nude 
These  formations  occur  most  frequently  iu  the  meninges,  the  choroi 
plexus,  and  the  pineal  gland,  and  in  the  new-growths  arising  in  these  r( 
gions.  Through  subsequeijt  calcification  they  lead  to  the  formation  t 
laminated  concretions  of  calcium  salts  (see  §  6G,  Fig.  103 ). 

Another  kind  of  hyaline  formation  probably  owes  its  origin  to  a  seen 
tory  activity  of  the  connective-tissue  cells.  This  may  be  designate 
srrreton/  connective-tissue  hyalin,  but  it  must  be  noted  that  under  this  ter: 
theie  is  included  a  variety  of  different  formations,  and  that,  as  in  tl 
l)r()ductiou  of  colloid,  the  cells  as  a  irJiole  may  he  converted  into  hyali't 
products. 

Further  belong  here  certain  granules  and  spherules  of  hyaline  a 
pearance  which  stain  especially  intensely  with  fuclisiii,  though  staiuiij 
also  with  methyl  violet,  gentian  violet,  etc.  ;  and  wliich  are  known  j 
J'urli.siiiojiliih'  bodies.  They  are  also  often  called  linssel's  bodies  fi'om  tlj 
fact  that  they  Avere  described  closely  by  Eussel,  who  regarded  them  li 
paiasitic  tission-fungi.  i 

I 
Fuchsinopliile  bodies  are  found  both  in  normal  and  in  slightly  altered  tissi? 
(adrenals,  various  mucous  membranes — as  that  of  the  stomach — in  the  brain,  splet? 
:in(l  lymphadenoid  tissues),  also  in  inflamed  tissues  (particularly  the  mucous  mej" 
branes,  for  example,  of  the  stomach), inflammatory  new-growths  (polypi  of  the  stomaci', 
and  in  connective-tissue  tumors.  They  are  partly  intracellular,  sometimes  in  grr: 
numbers,  and  partly  extracellular.  They  are  to  l)e" regarded  as  cell-products,  piobal' 
of  the  nature  of  a  cell-secretion,  or  formed  as  the  result  of  the  disintegration  of  thece'. 
Of  their  genesis  and  their  composition  nothing  definitely  is  known;    it  is  possible  tit 


t 


COXXECTIVf:-TlSSl'E    IIYALIX.  225 

they  have  a  close  rehxtionship  with  the  mast-cells.  Those  occurring  in  the  brain  and 
spinal  cord  are  generally  classed  with  the  corpora  aniylacea  (§  V)'A).  even  when  they 
give  no  specific  iodine  reaction. 

Finally,  there  should  he  considered  in  this  connect  inn  (he  lar.ircr  A//a////c  spherules 
and  casts  uf  tubes  (cluinged  blood-vessels)  resembling  epithelial  colloid,  which  are  not 
infrequently  seen  in  s;ircomata  (see  Endothelioma  and  Angiosarcoma),  inasmuch  as 
these  formations  are  also  to  be  regarded  as  products  either  of  a  secretory  or  of  a 
degenerative  process  on  the  part  of  cells. 

The  siynijlcance  of  the  granules  of  eosinophile  and  mast-cells,  as  well  as  the  neu- 
trophile  granules  of  the  leucocytes  (which  stain  with  a  neutral  dye  obtained  through  a 
mi.xture  of  acid  fuch.sin  and  basic  methyl  green),  cannot  be  jjositively  stated  at  the 
present  time.  Ehrlich,  Ileidcnhain,  and  Lowit  regard  tlie  granules  of  the  leucocytes 
as  secretory  products  of  a  specific  metabolism  of  the  cells  in  which  they  are  found,  so 
that  these  cells  may  be  looked  upon  as  imicellular  glands.  On  the  other  hand.  Wcidcu- 
reich  regards  the  eosinophile  cells  as  lymphocytes  that  liave  taken  up  the  fragments  cf 
disintegrated  red  blood-cells,  their  nuclei  in  this  process  assuming  the  polyinorphous 
form. 

Arnold  regards  the  cell-granules  which  may  be  demonstrated  by  means  of  especial 
stains  in  leucocytes,  pus-corpuscles,  bone-marrow  cells,  and  also  in  other  cells,  not  as 
granules  of  .secretion,  but  "s  repre.senting  changed  structural  elements  of  the  cell  aris- 
ing out  of  a  metamorphosis  of  the  plasmosomes — that  is,  the  microsomes  of  the  cell- 
cytoplasm  (see  §  SO).  Acidophile  cells  may  be  transformed  into  basophile,  or  the  reverse 
may  occur;  these  phenomena  are  to  be  regarded  as  the  expression  of  different  stages 
of  development  with  changes  in  the  physico-chemical  properties.  Hesse  has  expressed 
a  similar  opinion. 

The  formations  described  in  §§  64  and  65  as  connective-tissue  Jiyalin  are  undoubtedly 
pathological  products,  which  differ  from  each  other  in  so  far  as  their  mode  of  origin  and 
their  chemical  composition  are  concerned.  Since  we  do  not  yet  know  the  natuic  of  the 
])rocesses  leading  to  these  hyaline  formations,  there  is  nothing  to  do  but  to  group  them 
according  to  definite  points  of  view. 

Ton  Recklinghausen  gives  to  the  term  Jiyalin  a  much  more  Cdrnjuchciisivc  nicaning 
than  I  do.  He  includes  under  the  head  of  hyaline  degeneration  dilTcrcnt  pathdiogical 
changes  which  I  have  placed  under  other  heads.  He  delincs  hyaliii  as  an  all)UMiiniiiis 
,  body  which  stains  intensely  with  eosin,  carmine,  picrocarniine,  and  acid  f  uclisin ;  is 
iioningeneous  and  strongly  refractive;  is  but  slightly  changed  by  acids;  and  in  its  re- 
sistance to  alcohol,  water,  ammonia,  and  acids  resembles  amyloid,  but  does  not  give  the 
iodine  reaction.  As  hyalin  he  includes  epithelial  colloid  and  flu;  hyaline  products  of 
.connective  tissue  cells,  as  well  as  hyaline  degeneration  of  the  ground  substance  of  the 
jconnective  tissue,  also  hyaline  tiirombi,  and  the  hyaline  coagula  of  inflanunatory  exu- 
jdates,  and  hj^aline  tissue-necroses.  According  to  this  author,  all  of  these  formations 
iresult  from  the  fusion  of  the  elements  of  neighboring  cells. 

!  From  their  external  appearance,  all  of  tliese  products  may  be  properly  designated 
Ihgalin;  but  the  following  varieties  must  be  recognized  :  epithelial  hyalin  (colloid,  kera- 
jtohyalin),  connective-tissue  hyalin  (hyaline  degeneration  of  the  ground-substance  of 
connective-tissue,  hyaline  products  of  cells,  and  cells  which  have  become  hyaline), 
hlood-hiialin  (hyaline  throml^i),  exudative  hyalin  (hyaline  coagula  of  exudates  on  mu- 
*cous  membranes,  .serous  surfaces,  inflamed  connective  tissue,  in  the  urinarj'  tulndes, 
itubercles,  etc.),  and //,vfl//nr //.s'.swe-neCT'oses.  In  the  case  of  connect i\'e-f issue  hy.-din  a 
distinction  must  ])e  made  Ix'tween  the  hyalin  formed  as  a  .secretion  in  tlie  cells  (clo.sely 
irelated  to  epithelial  colloid,  in  its  mode  of  origin),  and  hyaline  degeneration  of  the 
ground-substance  of  connective  tissue. 


Literature. 

(Hyaline  Froducts  of  Comieetive-tissur  CcUs  uiid  Lruron/tr.sj  Crll- 
granules. ) 

A-ltmann:  Die  Elementarorganismen  u.  ihre  Beziehungen  zu  den  Zellen.  Leipzig.  1890. 
A.rnold:  Ueher  Granulafarbung  lebcuder  Leukocvfen  und  Gewebe.  Vircii.  Arcli.,  157 
1        Bd.,   1899;    1.59  Bd.,    19(10;    Farbenwechsel  (Jer  Zellgranida.     Chi.  f.   allg.    I'ath., 

X..  1899;  Vitale  Granulafarbung  in  Kuorpelzellen,  Muskelfasern.  und  GangHenzd- 
'       len.     Arch.  f.  mikr.  Anat.,  55  Bd.,  1900;  A.  f.  mikr.  Anat.,  55  Bd.  u.  Anat.  Anz., 
1       xxiv.,   1903. 
'Ballowitz    Ehriich'sche  granulirte  Zellen  l)ei  wintersclilafenden  Tliiercn.     An.  Anz., 

vi..  1891. 
15 


22G  THE    RETROGRADE    CHAXGES. 

Ehrlich:  Physiol,  u.  Pathol,  d.  versch.  Formen  d.  Leukocyten.  Zeitschr.  f.  klin.  IMed., 
i..  1880;  Granulirte  Biudegewebs/elkni  u.  eosiuophile  Leukocyten.  Arch.  f. 
Anat.,  Phys.  Abth.,  1879;  Uutersuch.  z.  Histologie  d.  Blutes.     Gesch.  Mittheil.,  i.. 

IS'.ll. 

Galeotti;  Die  Granulationen  in  d.  Zellen.     Monatsschr.  f.  Anat.,  xii.,  1895. 
Goldmann:  :\Ialignes  Lyniphnm.     Cbl.  f.  allg.  Path.,  iii.,  1892. 
Hansemann:  llyaliuc  Zclleu  in  JMageupolypen.     Virch.  Arch.,  148  Bd.,  189T 
Heidenhain:  Histol.  u.  Physiol,  d.  DiinndarrHschleimhaut.    Pfluger's  Arch.,  23  Bd., 

Suppl.,  1888. 
Hesse:  Granula  der  Zellen  des  Knochenmarkes.     V.  A.,  167  Bd.,  1902  (Lit.). 
Klien:  Russel'sche  Fiichsinkorperchen  u.  Altmann'sche  Granula.     Beitr.   v.  Ziegler, 

xi.,  1892. 
liOwit:  Neubildung  u.  Beschaffenheit  d.  weissen  Blutkorpercheu.     Beitr.   v.  ZiesxkT, 

X.,  1891. 
Lubarsch:  Fuchsiukorper  u.  Corp.  amylacea.     Ergebn.  d.  allg.  Path.,  1895. 
Mai'wedel:  VeriUid.  d.  Kuochenmarks  bei  eiterig.  Entzilnd.     Beitr.  v.  Ziegler,  xxiii., 

1897. 
Neumann:  Mastzeileu  bei  path.  Verand.  ini  Gehirn.     Virch.  Arch.,  122  Bd.,  1890. 
Prus:  Fuchsinophile  Degeneration.     Cbl.  f.  allg.  Path.,  vi.,  1895. 
Ranvier:  Traite  technique  d'histologie,  Paris,  1875-1888. 
Rosenheim:  Mastzeileu  im  Nervensysteni.     Arch.  f.  Psych.,  17  Bd.,  1886. 
Russel:  Characteristic  Organism  of  Cancer.     Brit.  Med.  Journ.,  ii.,  1890. 
Saltikow:  Hyaline  Korper  in  Magenpolj^pen  u.  and.   Gew.     Yirch.  Arch.,  153  Bd., 

1N98. 
Sanfelice:  Experim.  Erzeugung  d.  Russel'scheu  Korperchen.     Cbl.   f.   Bakt.,  xxiii.,, 

IS'.I.S.  I 

Sclireiber:  Markzellen  (Klasmatocyten).    Munch,  med.  Woeh. ,  1903.  ! 

Tettenhammer :  Entstehung  d.  acidophilen  Leukocytengranula.     Anat.  Anz.,  viii.,'| 

isicj.  : 

Thorel:  Hyaline  Korper  in  Magen-  u.  Darmschleimhaut.     Virch.  Arch.,  151  Bd.,  1898.: 
Teuton :  Russel'sche  Fuchsinkorp.  u.  Goldmann'sche  Kugelzellen.     Virch.  Arch.,  132' 

B(l.,1893. 
Wolff:  Bedeutung  der  eosiuophilen  Zellen.     Beitr.  v.  Ziegler,  xxviii.,  1900  (Lit.).  ; 

[See  also  ^  64. 

XIII.  Petrifaction  of  the  Tissues  and  the  Formation  of  Concretions 
and  Calculi. 

§  66.  It  is,  on  the  whole,  of  rather  frequent  occurrence  for  firm  crys 
talline,  or  aniori^hous,  granular  masses  to  be  deposited  in  various  part' 
of  the  body-tissues;  and  when  such  deposits  are  of  such  extent  as  t(! 
cause  hardening  of  the  affected  tissue,  the  resulting  condition  is  knowi! 
as  petrifaction,  or  when  the  deposit  consists  of  lime-salts  (particularlj^ 
phosphates)  as  calcification. 

The  deposit  may  occnr,  in  the  first  place,  in  a  tissue  which  forms  ail 
integral  element  of  an  organ,  and  which  bears  its  normal  relation  to  th«J 
surrounding  tissues.  In  other  cases  it  takes  place  in  portions  of  tissut 
which  have  been  loosened  from  their  surroundiugs ;  or  insoluble  sub^ 
stances  ^^llich  have  become  changed  into  a  fijin  state;  or,  finally,  ii 
foreign  bodies  which  have  entered  the  body  from  without,  and  form  th 
centres  of  a  pi-ocess  of  incrustation.  j 

In  the  first  case  there  arise  petrifactions  of  the  tissues  ;  in  the  see] 
ond,  free  concretions  and  calculi.  It  is  to  be  noted,  however,  that  ur 
der  certain  conditions  free  concretions  may  become  firmly  attached  t,' 
the  tissnes  of  the  organ  in  which  they  lie,  by  means  of  tissue-proliferf 
tions  extending  into  or  surrounding  them.  On  the  other  hand,  a  calc 
fied  poi'tion  of  tissue  may  in  the  course  of  time  gradually  become  looseue 
from  its  sunouiidings  and  ultimately  form  a  free  concretion. 

A  deposit  of  lime  salts  occurs  in  the  form  of  very  fine  colorless  grar 
ules  (Fig.  96)  which  when  treated  with  silver  (von  Kossa)  take  on 
black  color  (formation   of  silver  phosphate)   (see  Figs.  97,  b,  99,  aci 


TISSL'E-PETUI  FACTION". 


227 


^^}^. 


KjSis^Mi- 


Fh;.  ixi.— I  iiicii: 
uf  theiu 


100,  B,  h).  When  lyiuo-  closely  croM^ded  together  they  bec«niu>  com 
fluent,  and  thus  oive  rise  to  the  foi-niation  of  chalky  foci  (Fig.  i>7,  h 
that  are  usually  not  sharply  circumscribed,  but  may  form  also  ciicuni 
scribed  spherical  concretions  (Fig.  !»S).  lu 
the  blood-vessels  the  calcification  may  l)egin 
either  in  the  connective  tissue,  musclefibres, 
or  in  the  elastic  tissue. 

The  cause  of  tissue-petrifaci ion  is  to  he  found 
chicfii/  in  ioatl  tissu('-chan(/cs,  in  that  the  dei>osit 
of  lime-salts  usually  occurs  in  ])laces  where 
the  tissue  has  already  died  or  is  in  ])i'ocess  of 
degeneration  and  necrobiosis.     For  e\am])le, 

lime  salts  may  be  deposited  in  jnilmonary  infarcts  (Fig.  99),  thiombi, 
in  necrotic  foci  arising  during    the  course   of   inliammations,   also  in 
dead  cells,   particularly  renal   epithelium  (Fig.   101,   d,   e),   and  liver- 
cells  (von  Kossa)  that  have  been  killed  as  the  result  of  intoxications 
(mercuric  chloride,  lead,  aloin,  bismuth,  copper  salts,  iodine,  and  iodo- 
form).    A  very  frequent  antecedent  to  the  deposit  of  lime-salts  is  the 
I  occurrence  of  hyaline  degeneration  of  connective  tissue,  ofteu  associated 
I  -with  a  deposit  of  fat.     This  occurs,  for  exaraj)le,  in  the  thickened  intima 
I  of  the  blood-vessels  and  heart-valves,  in  the  media  of  the  mediuni-sizcd 
arteries,  particularly  in  the  extremities,  in  inflammatory  new-formations 
of  connective  tissue  (for  example,  in  the  serous  membranes),  in  the  con- 
nective tissue  of  the  kidney  pyramids  of  old  people  (Fig.  100,  A,  B), 


Fig.  97. — Calcification  of  tlie  media  of  tlie  femoral  artery.      (Silver   i>rei)aratioii. ) 
b,  media;  c,  adventitia. '    X  40. 


Intlma; 


I  and  in  degenerated  thyroid  glands.     In  dying  adipose  tissue  (fat  necrosis 
in  the  neigliWoiJiood  of  the  pancicas)  ciialky  soap  may  be  formed. 

The  hyaline  cliaracter  of  tlie  (h'generated  connective  tissue  shows  avcU 
I  both  in  staining  with  Van  Gieson's  and  with  sim])le  haMnatoxylin.  In 
I  the  case  of  the  latter  stain  the  calcified  connective  tissue  (with  the  excep- 
tion of  that  fully  calcified)  becomes  a  diffuse  dark  blue  color  (Fig.  100,  A, 
I  c).  The  same  staining  reaction  occurs  also  in  the  case  of  calcified  nec- 
!  rotic  cells  (Fig.  101,  d,  e).  This  reaction  holds  good  only  for  the 
I  deposit  of  carbonates  and  phosi)hates,  Imt  not  for  tlie  oxalates  of  lime. 
In  rare  cases  there  may  occur  a  deposit  of  lime-salts  in  organs  Avhich 


228 


THE    RETROGRADE    CHANGES. 


show  but  slight  changes — for  example,  in  the  lungs.  Since  in  part  of 
such  cases  there  is  found  at  the  same  time  a  more  rapid  absorption  of 
the  skeleton  (senile  atrophy  of  the  bones,  destruction  of  the  bones  by 
tumors),  this  deposit  is  regarded  as  metastatic  in  nature,  due  to  the  over- 
loading of  the  blood  with  lime-salts.  Even  under  these  circumstances 
the  immediate  cause  of  the  calcification  is  local,  and  is  dependent  upon 


Fig.  98.— Calcified  vessels  in  the  cerebellum.      (Alcuhul,  ha'iuato.xyliii.)      X  100, 

retrogressive  changes— in  the  lung  tissue  (senile  atrophy,  obliteration  of  i 
vessels,  venous  congestion)  ;  and  the  increased  absorption  of  the  skeleton' 
is  but  a  favoring  factor.  According  to  investigations  of  Kockel  andj 
Kischensky  the  elastic  lamella  of  the  small  and  medium-sized  vessels  iui 
particular  become  calcified,  but  the  elastic  fibres  and  caf)illaries  of  the' 
alveolar  septa  are  also  involved.  ' 

The  calcification  may  affect  either  small  or  large  areas,  and  in  the! 
latter  case  causes  a  hardening  and  white  coloration  of  tlie  tissues.  Oc-j 
casionally  it  appears  in  the  form  of  sharply  circumscribed  spherical,  or, 


1"  ?V.<*^y5,lS.-ft:-:?»:f, 


Fig.  99.- 


-Calcification  of  a  necrotic    luns?  in  the  periphery  of    a    hiemorrhagic    infarct    six  j 
weeks  old.     (Formalin,  silver  treatment.)     X  100.  , 


nodular  (Figs.  102  and  103,  n,  b,  c),  or  long  spicule-like  formatiori 
(Fig.  103,  (1),  or  as  cactnslike  formations,  and  there  arise  in  consequeno 
concretions  lying  within  the  tissue  that  occasionally  may  be  recognize 
even  with  the  naked  eye.  Under  physiological  conditions  such  concr(' 
tions  are  found  in  the  form  of  laminated  chalky  spliernles  in  the  pine;; 
gland  and  the  choroid  plexus,   forming  here  the  so-called  brain-sar 


CALCIFICATTOX. 


229 


(acervulus  cerebri).  xVs  pathological  formations  they  occur  in  different 
regions  of  the  onter  and  inner  meninges;  in  many  tumors  of  the  same 
(psaninionui  or  sand  tnmoi's,  Fig.  102),  also  in  caseous  nnusses  (Fig.  102, 
b)  or  in  indurated  connective  tissue  (Fig.  102,  a').     The  origin  of  these 


::^si?i^?^Si?^<r.v^?^ 


3^^^~V 


Fig.  100. — Hvaline  degeneration  and  calcification  of  the  connective  tissue  of  the  kidney 
papillse.  A,  Stained  with  hematoxylin  and  eosin.  B,  Treated  with  silver  nitrate,  a.  Collecting 
tubules;  b,  blood-vessel;  c,  connective  tissue  showing  hyaline  degeneration  and  calcification.     X  300. 

formations  may  be  best  studied  in  the  jxsammomata  and  is  oixlinarily  to 
be  referred  to  a  transformation  of  tissue  cells  (Fig.  103,  a,  b,  c),  or  of 
fibrous  connective  tissue  (d)  into  a  hyaline  mass  that  inay  at  tirst  still 
contain  nuclei  (a),  and  later  loses  them  (b,  e),  and  then  takes  up  lime- 
salts.  Spherical  concretions  arise 
chiefly  from  hyaline  masses  formed 
from  cells  (a,  b,  c) ;  and  spicules  (d) 
arise  through  the  calcification  of 
hyaline  connective  tissue,  but  spher- 
ical concretions  (e)  may  arise  also  in 
hyaline  connective  tissue.  The  con- 
nective tissue  which  undergoes  de- 
generatidii  and  calcification  is  usually 
ordinary  connective  tissue,  but  cal- 

i  careous  spicules  and  round  concre- 
tious  may  develoi)  also  in  degener- 
ated vessel -walls. 

A   true    formation    of   bone    or 

'  ossification  may  follow  the  calcifica- 
tion of  a  tissue,  either  as  the  result 

I   of  a  new    tissue-fornuition,   or  of  a 

I  metaplastic    dfrH<>p)i>rtd    of    o-ssroiis 

■  tissue.     This  has  been  observed  most 

I  frequently   in   the   media   of  calci- 

1  fied  blood-vessels  of  the  extremities, 

I  but  it   may   occur  also   in  calcified 

i  lymph-glands,  in   the  neighborhood 

i   of  calcitied    necrotic    areas   in    the 

j  lungs,  and  in  thickened  serous  mem- 
branes, etc. 


Fk;.  101.— ralcill."ii 
[11-  kidncy-iiiliulfs  U 


'?*.  Sii' 


epitllfliiim   of 

lilHMll-    iH.iSOll- 

IMIl.'llt    (li.'il 


ruliuli-s;  )i.  Iiilmle  ujlh  (li'S(|ii;irii.il.'(|  i-pillif- 
liuiii :  c,  tulmie  with  ilfsciuiirniiifd  anil  n(irr)tic 
epithfliurn  p<is.>iP.ssinK  no  nuclei ;  W,  r.  tubule 
with    degenerated    and    calclUed   epithelium. 

xyoo. 


230  THE    RETROGRADE    CHANGES. 

According  to  tlie  investigations  of  Gierke,  calcifying  tissues  (fcetal  bones,  the 
enamel  anlage  of  the  dentine,  sand  bodies  of  the  choroid  plexus,  placental  calcifications, 
calcified  ganglion-cells)  contain  more  or  less  iron,  and  there  occur  also  iron-containing 
cell-necroses  (epithelial  casts  in  sublimate  poisoning)  which  stain  like  calcified  tissue, 


^•;!;' 

% 

r;   ;: 

) 

e-^  1.-^'       0, 

-.' 

M         ^'    ^/-^ 

«L^ 

>l 

i^ 

-^#2.^ 

~^ 

,^«^o 

«a  N 

. .  J^  \«» 


Fig.  ] 02.— Calcareous  concretions,    fl.  Concretions  from  an  inflamed  omentum ;   h,  calcareous  masses 
from  a  tuberculous  lymph-gland  which  had  undergone  caseation.    X  200. 

Fig.  103. —Section  from  a  psammoma  of  the  dura  mater,  with  concretions.  (Alcohol,  picric  a(i(], 
haematoxyiin,  eosin.)  a.  Hyaline  nucleated  splnTule  with  enclosed  calcareous  granule ;  h,  calcareous  con- 
cretion with  hyaline  non-nucleated  caiisule,  emin'ildcil  in  fibrous  connective  tissue;  c,  calcareous  concre- 
tion surrounded  by  hyaline  connective  tissue;  (/,  calcareous  spicule  in  connective  tissue;  e,  calcareous 
spicule  containing  three  separate  concretiuus,  eiubedded  in  the  connective  tissue.    X  175. 

but  are  not  calcified.     In  other  cases  (fidlj'  developed  bone  in  extrauterine  life,  calci- 
fied thrombi  and  calcified  vessels)  iron  is  not  present. 

Klotz  (Jour,  of  Exper.  Med.,  1905,  1906)  suggests  that  the  formation  of  calcium 
soaps  is  the  first  step  in  the  formation  of  pathological  masses  of  calcification,  these 
soaps  later  undergoing  a  transformation  into  the  less  soluble  phosphate  and  carbonate, 

M\'lh  {Jour,  of  Ei'per.  Med.,  1905)  found  but  minute  traces  of  calcium  soaps  in  I 
calcifying  matter.     It  is,  therefore,  probable   that  calcium-soap  formation  may  be  an  ' 
important  step  in  the  process  of  pathological  calcification,  but  is  not  an  essential  one. 
The  especial  affinity  of  calcium  for  cartilage,  hyaline  connective  tissue,  etc.,  cannot  at 
present  be  explained. 


Literature. 

{Galcification  of  Tissues,  and  Formation  of  Concretions  in  the  Tissues.) 

Arnold:  Ban  und  Entwickelung  der  Psammome.     Virch.  Arch.,  52  Bd.,  1871. 
Aschoflf:  Ycrkjilkung.    Ergeb.  d.  a.  Path.,  viii.,  Wiesbaden,  1904  (Lit.). 
Diemer:  Kalkublagcrung  in  d.  Serosa  des  Herzens.     Zeit.  f.  Heilk.,  xx.,  1899. 
Ernst:  Ucber  Psaimnome.     Beitr.  v.  Ziegler,  xi.,  1892. 
Friedlander:  Verkalkung  der  Ganglienzellen.     Virch.  Arch.,  88  Bd.,  1882. 
Golg-i:   I5au  und  Entwickelung  der  Psammome.     Virch.  Arch.,  51  Bd.,  1870 
Gottschalk:  Ueber  die  Einwirkung  des  Aloinsauf  die  Niereu.     Inauff.-Diss.,  Leipzig, 

1882. 
Kaufmann:  Die  Sublimatintoxication,  Berlin,  1888;  Virch.  Arch.,  117  Bd.,  1889. 
Kischensky:  Kalkablagerungen  in  Lunge  und  Magen.     C.  f.  a.  P.,  xii.,  1901. 
Kockel:  Kalkincrustalion  d.  Lungemewebes.     Deut  Arch.  f.  klin.  Med.,  64  Bd.,  1899. 
V.  Kossa:  Ki'instlich  erzeugbare  Verkalkungen.     Beitr.  v.  Ziegler,  xxix.,  1901. 
Leber:  ('Diijunctivitis  petrilicans.     v.  Gr?.efe's  Arch.,  li.,  1900. 
Leutert:  Die  Suhlimatiiitoxication.     Fortschr.  d.  Med.,  xiii.,  1895. 
Levi:  Untorsiiclningcn  iilxr  den  Ban  und  die  Entstehung  der  Concretionen  in  Psam- 

momen  der  Dura  mater  u.  der  Kalkplilttchen  in  der  Arachnoidea  spinalis.     Inautr.- 

Diss.,  Freibm-g,  1890. 
Litten:  Der  liilmorrhag.  Infarkt,  1879;  Verkalkungen  in  d.  Nieren.      Virch.   Arch., 

N;5Bd.,  1881. 
Mallory :  Calcareous  Concretions  in  the  Brain.     Journ.  of  Path.,  ii.,  1894. 
Meyer:  Structur  imd  Entstehung  der  Sandkorper.     Virch.  Arch.,  143  Bd.,  1896 


i 


DEPOSITS    OF    I  RIC    ACID. 


231 


Neuberger:  TJcbcr  die  "Wirkuug  iks  Subliinutes  luif  die  Niore.  Beitr.  v.  Zicgler,  vl„ 
1SS!»;  Tebcr  Kalivablagenins  in  den  Nieren.     Arch.  f.  exp.  Path.,  27  Bd.,  1S90. 

Paltauf:  rcb(>r  Pliosphorvergittnng.     Wien.  ivlin.  Woeh..  1SW8. 

Rey :  Ausschcidung  n.  Resorption  des  Kidivs.     Arch.  f.  exp.  Path..  35  Bd.,  189'). 

Bicker:  Vcikalkung  und  Steinbildnng.     Ergebn.  d.  allg.  Path.,  iii.,  lSi)7. 

Roth:  VcrkalknugderPnrkinje'sehen  Zellen.     Virch.  Arch.,  53  Bd.,  1ST!). 

Saikowsky:  Veranderungeu  ini  Orgauismns  durcli  Quecksilber.  Vireh.  Arch.,  37 
15(1..  ISliO. 

SchujeninofF:  :\ruskelverkalkuiig.     Zeit.  f.  Ileilk..  xviii.,  1897. 

Steudener:  Zur  Ktnntiiiss  drr  Sandgeschwiilste.     Vireh.  Arch.,  50  Bd.,  1870. 

Virchow:  Kalknietastascn.  Virch.  Arch.,  8  u.  9  Bd.  ;  Die  krankhaftcn  (Jesclnviilste, 
ii.,  Berlin,  1SG5;  Verkalkung  abgestorbcncr  Gcliirii/.cllcn.  Virch.  Arch.,  5U  Bd., 
1870;  Cyauquecksilbervergiftung.     jMuneli.  nicd.  Woeh.,  1888. 

Werra  :  Folgeu  d.  vorubergeh.  u.  dauernd.  Ver.sehlnsses  d.  Nierenartcrie.  Virch. 
Areh.,  88  Bd.,  1882. 

"Wildbolz  :  Kalkkonkremente  in  dcr  Ilaut.    A.  f.  Derm.,  70  Bd.,  1904 

Zanda  ;  Entwickeluug  der  Osteonie  der  Arachu.  spinalis.  Beitr.  v.  Ziegler,  v.,  1889, 
See  also  §  68. 


§  67.  The  more  common  petrifactions  consist  of  deposits  of  pliosi)hate 
of  lime,  sometimes  of  carbonate ;  Mitli  these  some  majiiiesiuiii  salts  may 
be  mixed.  Under  especial  conditions  there  occur  also  deposits  of  uric- 
acid  salts ;  par- 
ticularly iu  the 
disease  known  as 
gout,  which  is  a 
chronic  disturb- 
ance of  the  gen- 
eral nutrition 
characterized  by 
a  uric -acid  diathe- 
sis leading  to  a 
deposit  of  uric 
acid  in  the  tis- 
sues. 

Gout  is  usually 
inherited,  and  but 
rarely  acquired ; 
it  occurs  most  fre- 
quently in  certain 
regions,  as,  for 
example,  in  Eng- 
land and  in  North  Germany;  and  is  very  rare  in  other  countries,  as  in 
South  Germany.  Of  the  ultimate  cause  of  the  disease  we  have  as  yet  no 
positive  knowledge.  It  is  characterized  chiefly  by  the  deposit  in  the 
body  of  uric-acid  salts,  chiefly  sodium  urate,  with  which  small  quanti- 
ties of  carbonate  and  i)liosi)hate 
of  lime  are  sometinu'S  associated 
(Fig.  104,  I)).  The  deiiosit  of 
these  salts  takes  i)lace  usiuilly 
during  acute,  typical  i)aroxysms 
chaiacterized  by  pain  and  in- 
llammation,  but  very  great  de- 
part uies  from  a  typical  coui.se 
may  occui-.  The  deposits  are 
found  in  the  kidneys,  skin, 
sul)cutaneous  tissue,  t  e  n  d  o  n 
sheaths,      tendon.s,      ligaments, 


Fig.  104.— Deposits  of  urates  in  the 
dyles  of  the  femur;  7>,  urate  deposits 
size. 


niee-jolnt,  in  a  case  of  jrout. 
on  tlie  cartilasc.     Two-thinis 


Tio.10.5.— Deposits  of  needle-shaped  crystals  of  sudi. 
um  urate  in  the  articular  cartilage.   (After  Lancereaux.) 


232 


THE    RETROGRADE    CHANGES. 


bursse,  and  articular  cartilages  (Fig.  104),  but  may  finally  be  present  in 
almost  all  the  organs.  The  metatarsophalangeal  joint  of  the  great  toe 
is  a  favorite  site  of  deposit,  and  often  the  first  part  affected.  The  de- 
posits consist  essentiallj^  of  clusters  of  fine  slender  needles  (Fig.  105),  in 
whose  neighborhood  the  tissues  are  degenerated  or  necrotic ;  and  from 
this  it  may  be  assumed  that  the  urates  entering  the  tissues  in  solution 
give  rise  to  the  necrotic  changes  in  the  latter. 

The  areas  of  necrosis  and  incrustation  are  at  first  of  small  size,  but 
occasion  iufianimation  and  tissue-proliferations  in  their  neighborhood. 
Later,  with  the  occurrence  of 
other  paroxysms  the  deposits 
become  larger,  so  that  large 
nodules  (the  so-called  tophl^ 
are  formed.  These  consist  of 
white,  plaster-like  masses,  and 
under  certain  conditions  may 
form  marked  nodular  thick- 
enings in  the  joints  and  ten- 
dons (Fig.  106). 

In  the  joints  the  articular 
cartilages  at  first  appear  as 
if  sprinkled  over  with  plaster- 
of  Paris  (Fig.  104,  h),  but  later 
the  white  masses  penetrate 
deeper  and  may  i)ermeate  the 
entire  articular  cartilage.  In 
the  kidneys  the  tissue-necrosis 
caused  by  the  uric  acid,  and 
the  resulting  inflammation 
may  lead  to  contraction  and 
induration  of  the  organ.  The 
deposit  affects  chiefly  the 
medullary  pyramids,  but  is 
found  also  in  the  cortex. 

According  to  Garrod  and 
Ebstein  the  acute  paroxysms 
in  gout  depend  upon  an  ex- 
cessive accumulation  of  uric 
acid,  either  as  the  result  of 
deficient  excretion  by  the  kid- 
neys (Garrod)  or  of  local 
changes  (Ebstein).  Accord- 
ing to  Pfeifler  the  gouty  pre- 
disposition is  due  essentially 
to  the  fact  that  the  uric  acid 
in  the  body -fluids  is  i)roduced 

in  a  form  which  is  soluble  with  difficulty,  and  tends  to  be  deposited  in 
the  tissues  where  it  may  collect  in  such  quantity  as  to  cause  a  localized 
necrosis.  The  symptoms  of  the  gouty  paroxysm  are  supposed  to  depend 
upon  an  increased  alkalinity  of  the  body-fluids  caused  by  especial  con- 
ditions, as  a  result  of  which  there  follows  a  partial  solution  of  the  de- 
posited uric  acid,  in  the  course  of  which  process  attacks  of  pain  and 
symptoms  of  inflammation  are  produced.  On  the  other  hand,  von 
Koorden  regai-ds  Ihe  foi-uiation  and  deposit  of  uric  acid  as  a  secondary 
process,  due  to  the  hx-al  action  of  a  special  ferment,  and  quite  iude- 


FiG.  10('.— Gouty  nodes  of  the  hand.     (After  Lancereaux.) 


CONCRETIONS. 


233 


pendent  of  the  an 
the  body. 


nd  coiiditi 


id   ill    ollirr    i»:ir(; 


Literature. 


(Gout  and  (loKti/  l)<j)().sits.) 

Aschoff:  Exper.  Hanisiiuiciibliigerunsion.     Vciii.  d.  jiatliol.  Gesell..  ii.,  Berlin,  1900. 
Berkart:  Path,  of  the  Gouty  Paroxysm.     Brit.  iMed.  .lourii.,  i.,  185)5. 
Cantani:  S|)eeielle  Pathol,  u.  Ther.  der  StolTweehselkraiikheiten,  ii.,  Berlin,  18S0. 
Charcot:    Jlaladies    iles    vieillards,    goutu    et   rheinnatisnies.      (Kuvres   conipl.,    vii., 

Paris.  1890. 
Duckworth:  Traite  de  la  goutte,  Paris,  189:3;  Die  Gicht,  Leipzig,  1894. 
Ebstein:  Die  Natur  u.   Beliandhmg  d.   Gicht,  Wiesbaden,   1883;  Verhandl.   d.   VIII. 

C'ongr.  f.  inu.  Med.,  Wiesbaden,  1889;  Beitr.  z.  Lehre  v.  d.  harusauren  Diathese, 

Wiesbaden,  1891. 
Ebstein  u.  Sprague:  Beitr.  z.  Analyse  gichtiscber  Tophi.     Yireh.    Arch.,    l-J.l  Bd., 


Freudweiler :  Exp.  Uuters.  liber  das  Weseu  d.  Gicht.     Deut.  Areh.  f.  kiln,  ^[ed.,  03 

15(1..  19U0. 
Garrod:  Die  Xatur  und  die  Behandlung  der  Gicht,  Wiirzburg,  1801. 
His:   Wirkuiig  dis  sauren  barns.  Natrons.     Deut.  Arch.  f.  klin.  Med;,  07  Bd.,  lUOO. 
Kolisch:  A\'esL'ii  und  Beliandlung  der  uratischen  Diathese,  Stuttgart,  1895. 
Kionka:  Vogelgidit.     Arch.  f.  exp.  Path.,  4-4  Bd.,  1900. 
Levison:  Die  harn.saure  Diathese,  Berlin,  1893. 

Likhatscheff:  Uratablagerung  naeh  Ureteruuterbiudung.     Beitr.  v.  Ziegler,  xx.,  1890. 
Minkowski:  Phys.  u.  Pathol,  d.  Harnsaure.     Arch.  f.  exp.  Path.,  41  Bd.,  1898. 
Mordhorst:  Eutstehung  der  Uratablagerungen.     Virch.  Arch.,  148  Bd.,  1897. 
V.  Noorden :  Pathologie  des  Stoffwechsels,  Berlin,  1893. 
Pfeiflfer:  Das  Wesen  der  Gicht,  Wiesbaden,  1891. 
Riess:  Gicht.     Eulenburg's  Realencyklop.,  1895. 
Rindfleisch:  Bildung  u.  Riickbildung  gicht.  Tophi.     Virch.  Arch.,  171  Bd..  1903. 

§  68.  Free  concretions  are  formed  in  the  first  place  in  the  various 
ducts  and  cavities  of  the  body  which  are  lined  by  epithelium,  as  in  the 
intestines,  in  tlie  ducts  of  the  glands  pouring  their  secretions  into  the  in- 
testine, in  the  gall-bladder,  urinary  passages,  and  respiratory  tract.  In 
a  certain  sense  the  concretions  formed  in  the  blood-vessels  and  serous 

cavities  might  also  be  included  in 
this  group,  although  they  are  for 
the  greater  part,  lirmly  united  to 
the  surrounding  tissues. 

All  free  concretions  possess  an 
organic  base  or  nucleus.  Thus  en- 
terolitlisyxluch  form  in  the  intes- 
tines have  a  nucleus  of  inspissated 
fteces,  or  foreign  bodies  which 
have  been  swallowed,  sucli  as  liairs 
(hezoar  stones  or  a'f/af/r())>il<r),  or 
indigestible  i)<)rti(nis  of  vrgclalilc 
food,  etc.,  in  and  about  whieli 
l)hosp]jates  (ammonium  -magne- 
sium phos[)hate  and  calcium  phos- 
phate), and  carbonates  are  deposited  in  varying  proportions  accoiding 
to  the  nature  of  the  food  ingested.  In  the  mouth-cavity  incrustations  ot" 
the  teeth,  known  as  dental  cah-uJ i  ov  tartar,  are  foi-med  l)y  tlie  dejxtsit  ot 
lime-salts  in  masses  consisting  of  mucus,  cell-detritus,  and  l)acleria.  In 
the  same  way  there  are  formed  in  th<'  duels  of  the  salirarji  f/hnids  and  pan- 
creas oval  or  .splierical  faceted,  or  ii  regularly  nodular,  glandilonii  conrrr- 
tions,  through  the  calcareous  impregnation  of  a  substance  derived  from 


tU'.d    stoiif.s    from    the 
Natural  size. 


the  epithelium  of  the  gland. 


234 


THE    RETROGRADE    CHANGES. 


m 


-beition   through  a  s>iiiall    chole^ttiiu  &tuiu    aftt 
rnuo\dl  of  the  cholehterin     X  H 


Bronchial  calculi  are  formed  by  the  calcification  of  thickened  bronchial 
secretion  ;  the  stones  found  in  veins  and  arteries  (phleboliths  and  arterio- 
liths)  from  the  calcification  of  thrombi ;  prostatic  calculi  through  the  cal- 
cification of  the  so-called  amyloid  concretions;  navel  stones  i\iYO\\^\\  the 
retention  and  incrustation 
of  desquamated  epithelium, 
hairs,  and  other  substances 
which  may  enter  the  navel - 
depression. 

The  Uliary  calculi  and 
(/all-stones  found  in  the  bile 
passages  and  gall-bladder  are 
in  part  small  granules,  and 
pailly  larger  spherical,  oval, 
or  faceted  stones  (Fig.  107), 
which  on  fracture  appear 
to  consist  purely  of  crystal- 
line masses.  By  the  em- 
ployment of  proper  methods 
it  may  be  shown  that  these 
stones  also  possess  a  nitro- 
genous ground-substance. 

According  to  their  essen- 
tial composition  gall-stones  may  be  classed  as  cholesterin,  cholesteriu- 
pigment,  bilirubin,  biliverdin-calcium,  and  calcium  carbonate  stones. 
The  first  two  varieties  are  the  most  common ;  they  present  a  rayed,  crys- 
talline, often  laminated  fracture ;  and  vary  in  color  and  in  their  mottling 
according  to  the  amount  of  bile-j)igment  present.      When  no  pigment  is 

present  they  may  be  color- 
less and  translucent. 

If  the  cholesterin  be  dis- 
solved out  of  a  cholesterin 
stone  by  some  suitable 
method,  it  will  be  found 
that  the  form  of  the  stone 
is  preserved,  and  a  delicate, 
for  the  greater  part  yellow- 
ish, mass  remains.  This, 
when  carefully  embedded 
and  cut  into  sections,  is 
found  under  the  microscope 
to  consist  of  a  delicate,  ho- 
mogeneous substance  (Fig. 
108)  which  shows  concentric 
stratification  and  radiating 
clefts  or  spaces  which  wore 
fonnerly  occupied  by  the 
crystalline  masses.  A  sim- 
ilar ground-substance  may 
be  demonstrated  in  other 
calculi  after  solution  of 
their  calcium  salts. 
There  can,  llietcforo,  l)c  no  doubt  that  gall-stones  are  also  the  result 
of  the  incrustation  (.f  an  oi-ganic  substratum,  which  is  in  all  probability 
derived  from  the  nuicous  membrane  of  the  biliary  passages  and  the  gall- 


^^0^^^:^:^,^^ 


Fig.  109.— T'ric-Hcid  infarct  of  I  he  new-born.  (Alcoho],  haema- 
toxyhn.  Drawn  from  a  preparation  that  liad  lieen  washed  in 
water.)     Transverse  s.Mtion  thrcuL'h  the  ))vrnmid  of  the  kidnev. 

"•  I  i-ansverse  section  (if  i liaiiLTd  (■oli,.,.tiiiir  tiil)Ule  from  tlie 

IKipilla:   ?..  dilated  collrctiiiL'  tulmle  llll.d  witli  iiric-aeid   con- 
y'ail'"*'    ''  '''""""^  "^  i-oiicretioiis  afirr  washinir  with  water. 


CALCULI. 


235 


bladder.  Gall-stones  occur  especially  in  advanced  years;  stagnation  of 
the  bile  favors  their  formation.  Inlhunniations  of  the  mucous  membranes 
of  the  bilc-passaiivs  (aiii;iocholitis)  lead  to  des(|uaniationand  dcsti-nction 
of  the  epithelium  (^eveiitually  also  to  escai)e  of  lencocytes),  and  in  the 
products  deri\ed  from  these  i)athol(t.i;i('al  chaii.ucs  bilirubin  and  choh's- 
terin  are  (lei)osited.  AVhen  once  a  ccuicretioii  is  formed  it  increases  in 
size  throu<;h  the  deposit  of  new  products  of  cell-disintei;iation  %vhich  be- 
come encrusted  Mith  cholesterin,  pi^inent,  and  calcium.  Accoi'diiii;-  to 
Xaunyu  the  originally  soft  nucleus  of  the  concretion  undei'goes  a  change, 
in  that  it  separates  into  fluid,  and  into  firm,  granular  masses  of  ])iginent- 
calcium  and  crystals  of  cholesterin  which  are  deposited  n])on  the  outer 
crust,  so  that  the  stones  may  at  times  contain  a  cavity  tilled  with  the  lluid. 
In  the  course  of  time  this  cavity  may  again  be  tilled  with  cliolesterin ; 
and  also  the  i)igment  and  calcium  in  tlie  remaining  portions  of  tlie  stone 


Fig.  no.— Coral-sbaped  stone  from  the  bladder    composed  of  calcium   oxalate  and  phosphate.    Natural 

size. 

Fig.  111.— Transverse  section  of  two  stones  from  the  bladder,  closely  fltted  together,  and  consisting  of 
sodium  urate  and  ammonium-magnesium  phosphate.    Natural  size. 


may  be  gradually  replaced  by  cholesterin.     Further,  calcium  caibonate 

may  also  be  deposited. 

The  cholesterin  masses  from  which  the  concretions  are  formed  are 

derived  chiefly  from  the  disintegration  of  epithelial  cells;  likewise,  the 

lime-salts  combining  with  bilirubin  are  also  furnished  by  the  mucous 

membrane. 

The   urinary   calculi,    gravel,    and   stones   are   also   comj^osed   of    an 

organic  ground-substance,  an  albuminous  stroma,  in  which  the  various 
j constituents  of  the  urine  may  become  deposited.  According  to  location 
j  we  may  distinguish  calculi  of  the  kidney  and  those  of  the  descending 
'urinary  ])assages.     In  the  kidneys  the  deposits  may  form  only  small 

granules  lying  in  the  tissue  itself,  or  in  i)art  also  freci  in  the  lumen  of 
:the  urinary  tubules,  in  the  latter  place  lying  in  the  inotluds  deiived 
i  from  the  disintegration  of  necrotic  epithelial  cells.  This  is  true  in  the 
!  first  place  of  the  calcifications  which,  as  mentioned  above,  occnr  In  the 
[necrosed  renal  epithelium  after  j^oisoning  with  corrosive  sublimate,  bis- 
'muth,  aloin,  coi)per-salts,  iodine,  phosphorus,  potassium  chromate,  and 
j  oxalic  acid.  The  same  thing  is  true  of  some  of  the  gouty  deposits. 
I  Finally,  belongs  here  the  so-called  uric-acid  infarct  of  the  new-born,  a  con- 


236 


THE    RETROGRADE    CHANGES. 


dition  characterized  by  the  appearance  of  yellowisli-red  stripes  in  the 
medullary  pyramids.  The  condition  is  not  infrequently  seen  in  children 
dying  during  the  first  five  weeks  after  birth.  The  epithelium  of  the 
tubules  is  usually  well  preserved,  but  in  places  desquamation  and  disin- 
tegration of  single  cells  may  be  found.  The  lumina  of  the  tubules  are 
filled  with  very  small,  colorless  or  yellow  granules  of  urates  or  uric  acid, 
which  at  times  show  fine  radiating  lines  (Fig.  109,  &).  On  solution  of 
these  granules  a  delicate  stroma  remains  (c).  If  as  the  result  of  the 
presence  of  the  infarct  further  changes  in  the  epithelium  of  the  tubules 
are  produced,  leading  to  the  formation  of  albumi- 
nous material  in  the  tubules,  single  granules  may 
under  certain  conditions  develop  through  accretion 
into  large  stones,  but  this  occurrence  is  rare. 

In  the  pelvis  of  the  kidney,  ureters,  urinary 
bladder,  urethra,  and  under  the  prepuce  concre- 
tions may  be  formed,  either  as  sand,  gravel,  or 
stones.  The  last-named  are  oval  or  spherical,  and 
may  be  smooth  or  rough  and  nodular,  not  infre- 
quently resembling  a  mulberry  or  mass  of  coral 
(Figs.  110  and  111).  When  several  stones  lie  close- 
ly together,  their  surfaces  may  become  faceted 
(Fig.  111).  Those  found  in  the  kidney  pelvis 
may  form  casts  of  the  cavity  and  of  the  calyces. 

When  examined  in  section,  urinary  calculi  are 
sometimes  homogeneous,  at  other  times  distinctly 
stratified  (Fig.  Ill)  or  show  radiating  lines.  Not 
infrequently  there  may  be  seen  a  nucleus  and 
several  zones  of  different  appearances.  The  crys- 
talline masses  lie  partly  in  the  spaces  of  the 
stroma,  and  partly  in  the  latter  itself;  and  it  may, 
therefore,  be  assumed  that  the  stroma  is  a  product 
of  the  mucosa  of  the  urinary  passages,  and  that 
its  formation  follows  catarrhal  inflammations  or 
toxic  necroses  of  epithelium  when  these  lead  to  the 
collection  of  mucus  or  cell -detritus  in  the  tubules. 

What  substances  are  deposited  in  a  given  case 
in  tlu;  products  of  the  mucous  membrane  depends 
upon  the  existing  conditions.  When  the  condi- 
tions favoring  stone-formation  are  associated  with 
a  uric-acid  diathesis,  or  if  the  excretion  of  uric- 
acid  salts  by  causing  tissue-necrosis  has  at  the 
same  time  produced  the  conditions  favoring  the 
development  of  concretions,  the  deposits  in  the 
organic  gr(»und  sul)stance  will  consist  chiefly  of 
urates.  Decomposition  of  the  urine  with  forma- 
tion of  anuuonium-niagnesium  phosphates  leads  to  the  production  of 
calculi  consisting  chielly  of  this  substance.  Cystin  calculi  may  be 
foi-med  M-hen  cystin  is  excreted  by  the  kidneys,  as  the  result  of  pe- 
culiar metamorphoses  of  albumin  in  the  intestine,  due  to  the  action  of 
bacteria  (Baumann,  von  Udransky,  Brieger).  When  once  a  stone  is 
fonned,  tlie  irritation  which  it  causes  upon  that  portion  of  the  mucous 
meml)i'ane  with  which  it  comes  in  contact,  as  Avell  as  the  decomposition 
of  the  retained  urine,  favors  its  further  growth  by  accretion.  Likewise, 
forcifpi  bodies  (Fig.  112),  which  have  in  any  way  entered  the  bladder 


Fig.  112.  —  Incrusted  lead- 
pencil,  13  cm.  long,  taken  from 
the    male    urinary 
Reduced  j'o. 


bladder. 


I 


CALCULI.  2.37 

from  without,  may  lead  to  the  fonnafion  of  ealcuU,  tlironuli  1  lie  irritation 
wliicb  tliej-  excite  in  the  mucous  membrane  of  the  bladtU'i-. 

Int(>stin;il  calculi  iire  much  uiorc  coiuiuou  in  liorscs  and  caltic  Mian  in  man;  since 
undigested  vegetable  material  and  hairs  wliicli  liavc  been  licked  oil"  are  of  freciuent  oc- 
ciirreuce  in  the  intestinal  canals  of  these  animals  and  t'onn  the  starting  |>oint  of  such 
concretions.  The  true  stoues,  -which  occur  especially  in  horses,  are  rather  lianl  masses 
consisting  chiefly  of  magnesium  phosphate ;  the  false  stoues  consist  of  hairs  and  vege- 
table fibres  which  are  nu)re  or  less  encrusted.  Occasionally  balls  are  foiuid  wliich  con- 
sist almost  wholly  of  liair  {mjagropiU  or  hezonr  stoncx).  In  ruminatiug  animals  they  are 
fouud  chiefly  iu  the  ruiuen  or  reticulum  ;  in  hogs,  more  fretjuently  in  the  small  intestine. 

According  to  Schuberg,  the  enteroliths  of  herbivorous  animals  consist  chiefly  of  car- 
bonates; those  of  carnivorous,  of  phosphates.  The  composition  of  those  found  in  man 
varies  according  to  the  food  ingested. 

Urinary  calculi  are  classitied  according  to  their  composition  as  follows: 

1.  Calculi  composed  cliicfy  of  nn'c  arid  or  uraten. 

Pure  uHc-ncid  ca\c\i\\  are  usually  small,  yellow,  reddish,  or  brownish  in  color,  and 
hard. 

StoiuxoDifiixtiiifi  of  //riftis  arc  rarely  pure.  They  are  usually  covered  ou  the  surface 
with  a  coatiiii;-  of  ("ilciuni  oxalate  and  annuonium-maiinesium  phosphate. 

2.  r<i/rin'i  roiniiosxl  rhiijlji  nf  jihosphatcs  and  car/ionafcx. 

To  this  class  belong  stones  composed  of  calcimn  /i/iox/j/aitf,  ninmonium-mnfinrxium 
pjwspluite,  and  calcium  carbonate.  The  last  two  varieties  are  rare.  Ail  these  calculi  are 
white  or  grayish-white.  The  triple  phosphate  stones  are  soft  and  friable,  the  others 
hard. 

3.  Stones  composed  of  calcium  oxalate. 

These  are  hard  and  rougli,  and  of  a  brown  color. 

4.  Cystin  calctdi. 

These  are  soft,  waxy,  and  of  a  brownish-yellow  color, 

5.  Xantliin  calculi. 

These  are  cinnabar-red  iu  color,  smooth,  and  have  an  earthy  fracture. 

ElMeia  and  A  /'•«?«/(>/■  succeeded  in  experimentally  producing  urinary  calculi  by  feed- 
ing animals  with  oxamide,  an  ammonium  derivative  of  oxalic  acid.  The  greenish-ycilow 
concretions  thus  produced  in  the  urinary  passages  of  dogs  and  rabbits  consisted  essen- 
tially of  oxamide;  on  section  they  presented  a  concentric  laminated  structure  showing 
radiating  striations.  They  were  found  likewise  to  possess  an  albuminous  stroma,  which 
was  derived  from  the  necrosis  and  desquamation  of  epithelium  caused  by  the  action  of 
the  uxamide  during  excretion. 

Literature. 

{Free  Concretions. ) 

Baumann  u.  v.  TJdransky:  Ueber  das  Vorkommen  von  Diaminen,  sog.  Ptoniainea 

bei  Cystinurie.     Ber.  d.  Deutsch.  chem.  Ges.,  xxi. ;  Zeitschr.  f.  phys.  Chem.,  1889. 
Brieger  u.  Stadthagen:  Ueber  Cvstiiiurie.     Berl.  klin.  Wocii.,  1889. 
Gushing:  (Call  stones  Lit.)     Bull."  Johns  Hopkins  IIosp.,  1898. 
Ebstein;   Die  Xatur  u.  Behandlung  der  Ilarnsteine,  Wiesbaden,  1884. 
Ebstein  u.  Nicolaier:  Kiinstl.  Dar.stellung  von  harnsauren  Salzcn  in  der  Form  v. 

Spliiirolithen.     Virch.  Arch.,  123  Bd. ;  Exper.  Erzeugung  von  Harnsteinen,  Wies- 

l)aden.  IH'JI. 
Fauconneau-Defresne :  Traite  de  raffection  calculeuse  du  foie  et  du  pancreas,  Paris, 

1S.-31. 
Fiirbringer:  Nephrolithiasis,  Calculi  renum,  Nierenconcremente.     Deut.  med.  Woch., 

181)0. 
V.  Genersich:  Harte  der  Concremente.     Virch.  Arch.,  131  Bd.,  1893. 
Hahn:  Nabelconcremente.     Beitr.  v.  Bruns,  xxvi.,  1900  (Lit.). 
Leube:  Darnisteine.     Ziemssen's  Ilandb.,  vii. 

Lewis  and  Simon:  Cystinuria  with  Diaminuria.     Amer.  Journ.  of  ]\Ied.  Sc,  1902. 
Mayer;  (Jalleiisteiidjildung.     Virch.  Arch.,  136  Bd..  189",. 

Master:  Beitr.  /..  Kenntniss  der  Cystinurie.     Zeitschr.  f.  phys.  Chem.,  xiv.,  1889. 
Moreigne;   La  evstinurie.     Arch,  de  med.  exp.,  xi.,  1899. 
Naunyn:   Die  (iallensteinkranklieiten.     Verb.   d.  X.  Congr.  f.   inn.  Med.,  Wiesbaden, 

1S91;  Klinik  der  Cholelithiasis,  Leipzig,  1892. 
Posner;  IStudien  uber  bteiubildung.     Zeitschr.  f.  klin.  Med.,  ix.  and  xvi. 


238 


THK    RETROGRADE    CHANGES. 


Bibbert:  Path,   Anat.  d.  Wurmfortsatzes  (Bildung  v.  Kothsteinen).     Virch.  Arch., 

132  Bd.,  1893. 
Schuberg:  Bun  u.  chem.   Zusammensetzung  v.  Kothsteinen.     Viich.   Arcii.,  90  Bd., 

isso. 
Shattock;  Calculi  of  Calcium  O.xalate  from  a  Cyst  of  the  Pancreas.     Jouru.  of  Path., 

iv.,  1896. 
Smith:  Concretions  and  Calculi.     Ref.  Handb.  of  Med.  Sc,  1901. 
Solger.   Ahlagerungen  im  Knorpel.     Arch.  f.  mikr.  Anat.,  34  Bd.,  1889. 
Spiegelberg:  llarusaureinfarkt  d.  Neugeboreuen.     Arch.  f.  exp.  Path.,  41  Bd.,  1899. 
Steinmann :  Schalen- und  Kalksteinbildung.     Ber.  d.  Naturf.  Gcs.  zu  Freiburg,  iv., 

ISS!). 
Stroebe:  Arbeiten  liber  Bildung  freier  Concreniente.     Cbl.  f.  allg.  Path.,  i.,  1890  (Lit.). 
Studensky:  Zur  Lehre  von  der  Bildung  der  Harnsteiue.     Deut.  Zeitschr.  f.  Chir.,  vii., 

ISTT. 
Tross:  Facettirte  Speichelsteine.     Beitr.  v.  Zicgler,  viii.,  1890. 

XIV.  The  Pathological  Formation  of   Pigment. 

§  GO.  Both-  counective  and  epithelial  tissues  in  various  parts  of  the 
body  coutaiu  normally  an  autochthonous  pigment,  which  lies  tvithin  the 
cells,  and  consists  either  of  yellow,  brown,  or  black  granules,  or  forms  a 
diffuse  yellow  or  brown  coloration  of  the  cells.  These  autochthonous  pig- 
ments are  known  as  melanin,  lipochrome, 
and  haemofuscin.  In  the  epithelial  tis- 
sues the  pigment  is  found  particularly 
in  the  lowest  layers  of  the  rete  Malpighii, 
which  contains  j)igment  in  all  the  pig- 
mented portions  of  the  skin,  also  in  the 
hairs,  iu  the  pigment-epithelium  of  the 
retina,  and  in  many  ganglion-cells.  In 
the  pigment-cells  of  the  skin  the  granules 
are  chiefly  yellow  and  brown;  in  the  epi- 
thelium of  the  retina  they  are  black.  In 
marked  pigmentation  of  the  skin  other 
cells  besides  those  of  the  rete  Malpighii 
contain  pigment.  Among  the  connective- 
tissue  cells,  which  most  frequently  con- 
tain yellow  or  brown  pigment-granules, 
are  the  cells  of  the  choroid,  sclera,  co- 
rium,  lieart-muscle,  muscularis  of  the  in- 
testine, and  pia. 

Tl:e  normal  autochthonous  pigments 
may  be  increased  under  various  physiol- 
ogical and  pathological  conditions.  For 
example,  during  pregnancy  the  pigmeyit  of 
the  skin  is  usually  more  or  less  increased 
(chloasma  uterinum),  particularly  in  bru- 
nettes. In  Addison^s  disease,  a  general 
disease  leading  to  cachexia  and  which  is 
(leiMMulcnt  upon  pathological  cxmditions 
of  the  adrenals  (see  §  20),  there  occurs  a 
decided  pigmentation  of  the  skin  as  a  re- 
sult of  an  increase  of  the  normal  pigment. 
Not  infrequently  spots  of  a  bronze  coloi- 
appear  in  the  mucous  membranes  of  the 

mouth.     Further,  iu  atrophic  conditions  of  the  heart  there  is  usually  an 
increase   of  the  normal  heart-pigment.      Yellow  pigmeut-grauules   also 


I 


Fig.  113.— Large  hairy  pigmented  mole 
over  tlie  back  and  buttocks,  with  scattered 
spots  of  pigmentation  over  trunk  and  j 
shoulders.     (After  Rohrlng.) 


1/ 


THE    PATHOLOGICAL    FORMATIOX    OF    PIGMENT.  239 

appear  in  the  xiolunlary  musdcn  in  oomlitions  of  atropliy ;  and  in  old  per- 
sons tlie  smooth  nni.sch'  of  the  iittrstiiic  always  contains  more  or  less  of  a, 
yellow  <i;rannlar  pigment,  so  that  stimetimes  the  onter  snrface  of  tiie  in- 
testine may  show  a  yellow  or  yellowish-brown  coloration. 

The  most  intense  grades  of  i)ath()logical  pigmentation  are  met  with 
in  firchles,  Jcntifiincs,  pkimentcd  moles  (Fig.  113)  -AMd  j)if/iiic)itcd  wart.s,  and 
in  hhick  meJdiiotic  /(n»or,s  (see  Chapter  \' III.).  'J'lie  amonnt  of  i)igment 
may  be  so  gicat  as  to  give  the  tissnes  a  pnrt^  black  color. 

The  pigment  lies  for  the  greater  i)art  inside  of  tissne-cells  {rltrotnato- 
phorcs),  more  rarely  in  the  intercellnlar  sid)stance.  Jt  is  eomi)osed  of 
yellow,  brown,  or  black  grannies;  not  infreqnently  individual  cells  may 
l)e  diffusely  pigmented.  In  Addison's  disease  the  pigment-giannles  are 
found  partly  in  epithelial  cells,  especially  in  those  lying  directly  ui)Ou 

the  connective  tissue  (Fig.  11-1, 
/  A,    a,   h,  and  B,  a),  and  part- 

"^T^*^  ly  in  branched  connective-tis- 

^         y^       sue  cells    (A,    e,   c,,   (/),    from 
i  which  pigmented  processes  ex- 

^M-  L        W        V      T'  tend  up  between  the  epithelial 

\^     ^   /^^  cells  (B,  c). 

In  the  pigmented  spots  of 
the  skin  and  in  melanotic  sar- 
conmta  the  pigment  is  })aitly 
contained  in  especially  differ- 
entiated connective-tissue  cells 
of  large  size,  and  partly  in  ap- 
parently normal  cells  of  the 
B  given  tissue,  very  often  in  the 

connective-tissue    cells   in  the 
neighborhood    of    the    vessels 

Fig.  114.— ^,  and  B,  Pigmented  cells  of  the  skin  from  oiwl    i.i    fl.ck  /^./illc;    r.f   -^li^  Trooo^l 

a  case  of  Addison's  disease  with  caseous  tuberculosis  of  auu    lU    llie   CeUS    OI    lUe  VeSSei- 

both  adreuals.     (Alcohol,  carmine.)     c,  Piiruieutcd  epi-  -walls 
theliuin  cells  from  the  deepest  layer,  in  a  seitldii  cut  at  '      '  ' 

right  angles  to  the  surface.    ^,  b,  Piguicnttd  t]iitliclial  lu     the     gangllOll-cells     the 

Sn,H;;:r  n:;';r;":;\t;?i;5i^'^:;'Sg,;^.!rr  ^t^^J^  pigment  is  composed  of  broNN-n 

pigrni-ntiil  ((pniiHrtivf-tissue  cells,  the  processes  of  which,        p-i-innlAc 

HI  yi.  im>h  li.tu.M-n  the  epithelial  cells;    (/,  pigmented       fe*  <^«"'»'»c>'>-    _  _  ,  .,      , 

icii-prn(cs.s(s.    ,.  :ij().  The  pigments  just  dcseiibed 

are  products  of  a  specific  cell- 
activity ;  and  we  must  suppose  that  many  connective-tissue  cells,  gan- 
glion-cells, and  muscle-cells  are  able  to  form  pigment  from  the  material 
[brought  to  them.  In  the  majority  of  cases  the  pigment  ap])eai's  to  be 
'formed  in  tlu^  places  where  it  is  found;  yet  different  investigations  make 
it  pi(tl)al)le  that  the  pigment  may  at  times  be  transixiited.  The  jtig- 
jiieiit  of  the  ei)idermis  and  of  the  liaii's,  at  least  in  i>art,  is  not  foiined 
lin  the  epithelial  cells  themselves,  but  in  branched  connecti\e-ti.ssue  cells 
!(Fig.  114  A,  c,  d,  and  B,  e)  which  lie  just  beneath  the  I'cte,  and  send 
iproces.ses  between  tlie  epithelial  cells,  through  which  the  ])ignient  is 
[transferred  to  the  latter. 

Tlie  fact  that  the  ]>igment  is  often  found  ])articulaily  about  the  l)lood- 
yessels  Avould  seem  to  indicate  that  the  matei-ial  from  which  it  is  foi-med 
is  derived  fi-om  the  blood,  and  many  authors  acce])t  without  (ju«'stion  the 
view  that  the])igmeiit  is  a  derivativeof  the  coloriiig-matlei-  of  the  blood. 
Against  this  view  is  the  fact  that  neither  in  the  blood  nor  in  the  neigh- 
horhood  of  the  blood-vessels  ai'e  there  present  evidences  of  an  escape  of 
the  red  blood-cells  or  of  a  disintegration  and  solution  of  the  same.     It 


240  THE    RETROGRADE    CHANGES. 

is,  therefore,  very  probable  that  the  pigment  is  formed  either  from  the 
circuhiting  albumin  or  from  the  albumin  of  the  cells. 

The  attempt  has  been  made  to  solve  this  problem  by  means  of  chemi- 
cal investigations;  and  the  results  obtained  up  to  the  present  time  favor 
the  theory  that  the  pigment  is  a  product  of  cell-activity,  and  is  formed 
from  albuminous  bodies.     The   different  forms  of  melanin,   in  which 
group  the  pigments  of  the  skin  and  choroid  are  usually  placed,  are,  ac- 
cording to  the  investigations  of  von  Xencki,  Sieber,  Abel,  Davids,  and 
Schmiedeberg,  nitrogenous  bodies  rich  in  sulphur,  but  a  ary  greatly  in 
composition.     According  to  Schmiedeberg  these  differences  depend  upon 
their  mode  of  origin,  inasmuch  as  these  pigments  represent  thejinal  prod- 
uct of  a  Jong  series  of  metamorphoses  of  album i n  ;  and  in  their  formation 
may  be  compared  to  the  develoj)nient  of  humus.     The  genuine  albu- 
minous bodies  do  not  furnish  the  material  for  the  building  up  of  this 
final  product  (Schmiedeberg),  but  it  is  derived  from  sulphur-containing  , 
bodies  formed  by  the  splitting-up  of  the  albumins,  and  from  which  cer-  , 
tain  carbon-containing  groups  have  already  been  split  off,  so  that  there  i 
arise  combinations  which  in  proportion  to  their  carbon-content  are  very  ! 
rich  in  sulphur,  and  from  these  the  melanins  are  formed. 

Iron  may  be  present  in  small  amounts  in  masses  of  melanotic  pig- . 
ment,  but  is  usually  absent  and  is  not  necessary  to  the  j)i*oduction  ofi 
melanin. 

In  the  case  of  a  very  abundant  formation,  melanin  may  be  excreted 
in  the  urine. 

Lipochrome  is  the  term  applied  to  the  coloring-matter  of  adipose 
tissue,  corpora  lutea,  ganglion-cells  (Eosin),  and  of  the  greenish  tumorsi 
known  as  chloromata  (Krukenberg).  Of  the  origin  and  nature  of  thisl 
pigment  nothing  definite  is  known. 

Haemofuscin  (von  Recklinghausen,  Goebel)  is  the  iron-free,  yellow- 
ish granular  pigment  found  in  heart-muscle,  smooth  aud  striped  muscle,! 
in  tlie  cells  of  the  glands  of  the  stomach  and  intestine,  in  the  lachrymal,| 
mucous,  and  sweat  glands,  the  seminal  vesicles,  and  adrenals.  Accord- 
ing to  von  Kecklinghausen,  this  pigment  is  derived  from  the  blood,  but 
it  has  not  yet  been  established  that  it  is  a  haemoglobin-derivative.  Th( 
sulpluir-content  (Rosenfeld)  makes  it  not  unlikely  that  the  haiuiofuscii- 
granules  belong  to  the  melanin  group.  It  is  a  striking  fact  that  whei 
treated  M'ith  "  fat -stains  "  the  hsemofuscin -granules  are  found  to  be  fat 
containing  just  as  lipochrome  stains  as  fat  (Lubarsch). 

According  to  von  EdlUker,    "the  pigment  of  the  hair  and  epidermis  is  derivec 
from  pigmented  connective-tissue  cells  which  lie  just  beneath  the  deepest  layers  o 
the  epithelium  of  the  hair-bulbs  and  of  the  rete,  and  send  processes  between  the  del, 
icate  cells  of   these  layers.     These  processes  divide  into  long  tine   raniitications  whiei 
lie  in  the  intercellular  spaces  and  may  even   penetrate   into  the    cells   themselvesl 
and  in  this  way  transfer  their  pigment  to  the  latter."     The  pigment  of  the  ganglioj 
cells  and  of  the  cells  of  the  retina  arises,  on  the  other  hand,  in  the  ectodermal  cell) 
themselves.    Jii(  hi  and  EJtrmann  agree  with  von  Kolliker.    AVn-// observed  that,  follow^ 
ing  the  transplantation  of  white  skin  on  to  the  surface  of  a  leg-ulcer  in  a  negro,  tL 
white  grafted  portions  became  wholly  black  in  from  twelve  to  fourteen  weeks;  and  1 
concludes  that,  in  the  pigmentation  of  the  epidermis,  pigmented  connective-tissue  eel 
penetrate  between  the  epithelial  cells  and  convey  pigment  to  the  latter.     Jlicroscopic; 
examination  showed  the  presence  of  such  pigmented  processes  between  the  epitheli: 
cells  at  a  time  when  the  latter  had  not  yet  become  pigmented.      Von   Wild  has  show 
tliatin  melanosarcomata  of  the  skin,  pigmented  connective-tissv.e  cells  may  penetra 
lictwccn  tlie  epiliiclial  cells.     Similar  pigmented  connective-tissue  cells  are  found  in  tl 
l)igniented  portions  of  the  skin  or  mucous  membranes  in  cases  of  Addison's  diseas 
usually,  however,  in  certain  areas  only  and  not  everj^where. 

Histological  studies  of  the  mode  of  formation  of  the  normal  pigment  in  vario 


I 


THE   AUTOCHTHONOUS    PIGMENTS.  211 

animals,  cliiefly  in  fishes,  amphiliia,  anrl  reptiles,  have  led  to  different  conclusions. 
Thus  Jariscfi  is  of  the  opinion  that  the  ])i,<;nicnt  of  the  skin  and  teeth  of  tadpoles  is  not 
!  derived  from  the  Idood,  but  is  a  product  of  the  ]>rotoplasni,  while  List,  on  the  other 
i  hand,  believes  that  the  pifjment  of  the  skin  of  fishes  and  amphibia  is  formed  from 
I  hiemoglobin.  Ehrmann  holds  that  the  melanotic  pigment  of  all  vertebrates  is  a  hafino- 
i  globiu-ilerivative.  Accordinji  to  Kromaycr,  the  pigment  of  the  skin  of  mammals  is 
j  derived  from  the  protoplasmic  fibrillffi  of  epithelial  cells  and  represents  a  degeneration- 
product  of  the  same. 
I  According  to  von  Fiirth,  neither  sulphur  nor  iron  is  necessary  to  the  formation  of 

melaniu.  The  melanin-molecule  contains,  however,  active  atom-groups  which  enalde 
it  to  combine  with  certain  com])lexes  rich  in  suli)hur  or  iron.  The  investigations  of 
Bcrtranil.  Bicdcrniann,  Schneider,  von  Fiirth .Gcssard,  and  others  make  it  very  i)robal)le 
{von  Fiirth)  that  theformation  of  melanotic  j)igment  depends  u|)on  the  action  of  an  ox- 
idative ferment  (tyrosinase)  upon  tjn-osin  or  other  hydroxylizetl  substances  of  an  aro- 
matic nature.  In  the  abimdant  formation  of  melaniu  in  tumors,  melanin  or  melanogen 
■  may  be  excreted  in  the  urine,  so  that  this  at  the  time  of  discharge  is  black  or  gradually 
1    becomes  black  when  exposed  to  the  air  and  light. 

[  According  to  Spieijkr,  the  results  of  the  chemical  investigation  exclude  the  deri- 

I    vation  of  melanin  from  hsematin.      He  has  also  demonstrated  the  existence  of  a  white 

i    chromogen  which  is  the  cause  of  color  of  white  sheep's  wool  and  of  gray  hairs. 

'  In  domesticated  animals  there  occurs  a  peculiar  melanosis  of  the  internal 

organs,    occasionally    associated   with  melanosis  of    the  subcutaneous  tissue.     The 

affected  organs  (heart,  lungs,  intestines,  etc.)  present  in  varying  munbers  grayish  or 

black  spots,  looking  like  ink-spots,  which  are  produced  by  the  deposit  of  pigment  in 

I    connective-tissue  cells  which  otherwise  a])pear  normal. 

I  Under  the  term  ochronosis  of  cartilage,  Virchow  described  a  peculiar  iron-free 

i  pigmentation  of  cartilage,  in  which  the  different  cartilages  of  the  body  show  a  brown 
or  black  color.  Besides  the  cartilages,  the  tendons,  capsules  of  the  joints,  the  perios- 
,  teum,  and  intima  of  the  aorta  and  the  heart  may  show  black  spots.  The  pigmen- 
'  tation  is  dependent  in  part  upon  a  diffuse  imbibition  of  the  tissue  and  in  part  upon 
the  deposit  of  iron-free  brownish  granules  in  the  cells  and  ground-substance.  The 
I  cartilage-tissue  shows  at  the  same  time  retrograde  changes,  fibrillation,  and  softening, 
i  The  pigment  probably  belongs  to  the  group  of  ■melanins.  During  life  the  urine  may 
:  have  a  brown  or  black  color.  The  condition  has  nothing  to  do  with  alkaptonuria 
;    (Langstcin). 

Literature. 

(AutochfJionons  Pif/menfs. ) 

Abel:  Hoinerk.  fiber  thier.  Melanine  u.  das  Hiimosiderin.     Virch.  Arch.,  120  Bd.,  1890. 

Askanazy :  Schwarze  Kristalle.     Ver.  d.  D.  path.  Ges.,  v.,  1903. 

Baumel:  Capsules  surrenales  et  melanodermie,  Paris,  1889. 

Bonnet:  UeberEingeweidemelanose.    Ver. d.phys.-m.  Ges.  zuWiirzburg,  24Bd.,1890. 

Bostrom:  Ueber  d.  Ochronose  der  Knorpel.     Internat.  Beitr.,  Festschr.  f.  Virchow, 

ii..  isni. 
Brandl  u.  Pfeiffer:  Farbstoff  melanotischer  Sarkome.    Zeitschr.  f.  Biol.,  26  Bd.,  1890. 
Caspary:   ('chcr  d.  Ort  d.  Bildungd.  Hautpigmentes.     Arch.  f.  Derm.,  xxiii.,  1891. 
Ehrmann:   Physiol,  u.   Pathol,  d.  Hautpigmentes.     Vierteljahrsschr.   f.  Derm.,  188.5, 

Js^^i);    j-.iit wickel.  u.  Wanderung  d.  Pigmentes  Ix'i  Ani))liil)ien.     Arch.  f.  Derm., 

xxi\-.,  1S'.I2;    Das  melanotische  Pigment,  t'assel,  ISiHi;    Biol.  C'bl.,  xix.,  1899. 
Pick:   Pigiiieiitierte  Xaevi.     A.  f.  Derm.,  59  Bd.,  1902. 

von  Furth:    Pliys.  u.  chem.  Unters.  lib.  melanot.  Pigment.     C.  f.  a.  P.,  xv.,  1904  (Lit.). 
Goebel:   I'igmentablagerung  in  der  Darmmuskulatur.     Virch.  Arch.,  136  Bd.,  1894. 
Halpern:  Feb.  d.  Verhalten  d.  Pigm.  in  d.  Oberhaut.     Arch.  f.  Derm.,  xxiii.,  1891. 
Hansemann:  Feber  Ochrono.se.     Berl.  klin.  Woch.,  1892. 
Heile:  ( )clironose.     Virch.  Arch.,  160  Bd.,  1900. 
:    Jarisch.:  llerkunft  des  Oberhautpigmentes.     Arch.  f.  Derm.,  xxiii.;    ilrgiinzh.,    b891, 
:  xxiv..   1892. 

V.  Kahlden:  Beitr.  z.  oath.  Anat.  d.  Addison'schen  Krankhcit.     Virch.  Arch.     114 

Hd.,  1888. 
Kaposi:   Pathogenese  der  Pigmentirungen.     Arch.  f.  Derm.,  xxiii.,  1891. 
'    Karg:   Fcher  Hautpigment  u.  Ernahrung  der  Epidermis.     Anat.  Anz.,  ii.,    1887,  p. 

^'77;   Studien  iiher  transplantirte  Haut.     Arch.  f.  Anat.  u.  Phys.,  1888. 
V.  Kolliker:  Woher  stammt  d.  Pigment    in  d.   I';pi(lermisgel)il<len?     Anat.   Anz.,  ii., 

1887;  Die  Entsteh.  d.  Pig.  in  d.  Uberhautgebilden.     Zeit.  f.    wi.ss.  Zool.,    xlv., 

1887. 
16 


242  THE    RETROGRADE    CHANGES. 

Kromayer:  Oberhautpigment.    Arch.  f.  nukr.  Anat.,  42  Bd.,  1893;  Zur  Pigmentlr:ie;e. 

Derm.  Zeit.,  vi.,  1897. 
Krukenberg-:  Grundziige  der  vergl.  Physiol,  der  Farlistoffe   u.  d.    Farben,  Heidel- 

lierg,  1887. 
Langstein:  Ochronose.     Hofmeisters  Beitr.,  iv.,  1903. 

List:   Herkunft  d.  Pigmentes  d.  Oberhaut.     Anat.  Anz.,  iv.,  1889,  Biol.  Cbl.,  x.,  1890. 
Lubarsch:   Fettlialtige  Pigmente.    C.  f.  a.  P.,  xiii.,  1902. 

Mackenrodt:   Unters.  iiber  das  Chloasma  uterinum.     In.-Diss.,  Halle-a.-Saale,  1885. 
Mertsching:  Studien  iiber  Keratohyalin  u.  Pigment.     Virch.  Arch.,  116  Bd.,  1SS9. 
Meyerson:   Zur  Pigmentfrage.     lb.,  118  Bd.,  1889. 
Miura:  Beitrag  zur  Kenntniss  des  Melanins.     lb.,  107  Bd.,  1887. 
V.  Nencki:  Farbstoffbild.  im  thier.  Korper.     Correspbl.  f.  Schw.  Aerzte,  xx.,  18!»(). 
V.  Nencki  u.  Berdez:  Farbstoffe  der  melanotischen  Sarkome.     Arch.  f.  exp.   Path., 

XX.,   188(j. 
V.  Nencki  u.  Sieber:  Weitere  Beitr.  z.  Kenntniss  d.  thier.  Melanins.   lb.,  xxiv.,  1SS8. 
Oppenheimer :  Pigmentbildung  in  melanotischen  Geschwulsten.     Virch.  Arch.,   106 

Bd.,  1886. 
Pforringer:  Entsteh.  d.  Pigmentes  bei  Morb.  Addisonii.     Cbl.  f.  allg.  Path.,  x.  1900. 
Philippson :  Ueber  Hautpigment.     Fortschr.  d.  Med.,  viii.,  1890. 
Post:   Pigmentirung  der  Oberhaut.     Virch.  Arch.,  135  Bd.,  1894. 
Raymond:  Pigmentation  dans  la  maladie  d'Addison.     Arch,  de  phys.,  iv.,  1892. 
V.  Recklinghausen:  Hamochromatose.     Tagebl.  d.  Naturforschervers.,  Heidelberg 

1889. 
Riehl:   Zur  Pathologic  des  Morbus  Addisonii.     Zeitschr.  f.  klin.  Med.,  x.;   Zur  Kennt- 
niss der  Pigmentbildung  im  menschlichen  Haar.     Vierteljahrsschr.  f.  Demi,  u 

Syph.,  1885. 
Rcihring:   Pigmentnaevus.     Deutsch.  med.  Woch.,  1893. 
Rosenfeld:    Das  Pigment  der  Hamochromatose  des  Darms.     Arch.  f.  exp.  Path.,   4> 

Bd.,  1900. 
Rosin:    Bau  der Ganglienzellen.     Deutsch.  med.  Woch.,  1896. 
Schmiedeberg:   I'cber  die  Elementarfonneln   einiger   Eivveisskorper  xmd   fiber    d'u 

Zusammensetzung  u.  d.  Natur  d.  Melanine.     Arch.  f.  exp.  Path.,  39  Bd.,  1897 
Sehrt:  Fetthaltige  Pigmente.     Virch.  Arch.,  177  Bd.,  1904. 
Senator:   Ueber  schwarzen  Urin  u.  schwarzen  Ascites.     Char.-Ann.,  xv.,  1890. 
Sieber,  N.:  Pigmente  der  Chorioidea  u.  der  Haare.     Arch.  f.  exp.  Path.,  xx.,  1886 
Spiegler :  Ueber  das  Haarpigment.     Beitr.  z.  chem.  Phys.,  iv.,  1903. 
Tietze:   Beobacht.  an  einem  Falle  v.  Melanosarkom  mit  Melanurie,  Cassel,  1894. 
Virchow:  Allgem.  Ochronose  der  Knorpel  u.  knorpelahnlichen  Theile.     Virch.  Arch, 

37  Bd.,  1866. 
Vuilleumier:  Pigment  de  la  peau  dans  quelques  cas  de  melanosarc.     Beitr.  v.  Zieg 

ler.  xxiii.,  1898. 
"Wagner:  Beitr.  z.  Kenntn.  d.  Ochronose.     I.-D.,  Freiburg  i.  B.,  1904. 
Wallach:   Beitr.  z.  Lehre  v.  d.  Melano.sarkomen.     Virch.  Arch.,  119  Bd.,  1890. 
V.  Wild:  i:in\vaiiilerung  v.  Pigment  in  d.  Hautepithei   bei  Melanosarkom.     Inaug 

Diss.,  Stras.sburg,   1888.     '  ^      ^   , 

Winkler:  Ursj)rung  des  Pigmentes.     Arb.  a.  d.  embryol.  Inst,  in  Wien,  1892. 

§  70,  Haematogenous  pigments— that  is,  the  pigments  wJwse  oiig 
from  the  coJor'nuj-uuitter  of  the  blood  maij  he  demonstrated  beyond  any  doiu 
— are  derived  usually  from  blood  whicii  bas  escaped  from  the  blood-vef 
sels,  or  has  undergone  coaguhition  within  the  vessels,  and  are,  tlierefor< 
dependent  upon  heal  changes.  In  other  cases  they  may  be  caused  by 
taking-up  of  blood-pigment  into  the  blood  or  by  a  change  in  the  bloo 
itself,  wliereby  granular  pigment  is  either  formed  in  the  blood,  or  litem* 
globin  ])asses  into  the  blood-plasma,  so  that  pigmentation  of  the  tissu«|j 
results  from  m.rtastatie  deposits  of  pigtnent.  Such  pigmentations  are  know'i 
as  h£emachromatoses.  jl 

liolii  large  and  small  extravasates  of  blood  very  soon  undergo  ce 
tain  changes  which  are  visible  to  the  naked  eye,  Extravasates  in  tl 
skin  become  tirst  brown,  then  blue,  followed  by  green,  and  finally  yt 
low.  Small  luemorrhages  into  the  tissues,  as  in  the  peritoneum,  pleup 
and  lungs,  may  show  for  a  long  time  as  reddish-brown  spots;  in  d 
composing  cadavei's  their  color  may  be  slate-colored  or  black.  Larj 
luemorrhages  into  tlie  tissue,  as  in  the  brain  or  lungs,  assume  after  a  ce 
tain  time  a  rust-brown  color,  which  later  changes  to  an  ochre-yello 


H.EMATOGEXOl'S    PTCMEXTS. 


243 


.1 


C  ?*  vT- J?^ 


'^ 


Fio.  115.—^,  Cells  containiiiff  amorphous  blood-pigment:  n, 
those  witb  few  large  fragments  of  red  blood-cells ;  /j,  c,  tbose 
containing  great  numbers  of  small  disintegration-products  of  red 
blood-cells;  B,  rhombic  plates  and  needles  of  haematoidin. 
X  500. 


yellow,  yellowish-browu,  or  brown  pigmeiitiition.  All  these  ehiinucs  of 
color  correspoiul  to  eertaiu  ch;iiij;es  in  the  luenio<»lobin  and  in  the  iron 
which  it  contains. 

Whene\  t'l-  a  hiemorrhaffe  occurs  in  the  tissues  or  into  a  body-cavity, 
a  certaiiA  portion  of  the  bh)t)(l-plasina  and  of  the  rr<Z  hlood-cvlls  maybe 
taken  up  unchanged  through  the  lyinph-vessels.  Another  portion  of  the 
corpuscles  gradually  loses  its  lurmoglobin,  the  ])ale  stroma  of  the  corpus- 
cles remaining.     The  escaped  lucmoylobin  diJ^Kses  through  the  surrounding 

tissues,  and  from  it  there 
aie  foiined  the  ditiferent 
products  which  gi\e  i-ise 
to  the  changes  of  color  in 
the  neighl)orhood  of  the 
extravasate.  A  pa  it  of 
the  absorbed  ha'niogh>l)in 
may  be  excreted  as  nrohi- 
lin  (urohdinuria) ;  another 
part,  on  the  other  hand, 
may  be  precipitated  in 
the  tissues  in  the  form  of 
granules  or  crystals.  The 
latter  are  yelloiri.sh-red  or 
ruhij-red  iliombic  plates  and 
needles  of  hcematoidin  (Fig. 
115  B)  ;  and  represent  a  freciueut  residuum  of  htemorrliages.  A  portion 
of  the  diffused  hsemogiobiu  may  also  be  taken  up  by  cells,  the  latter 
thereby  acquiring  iu  part  a  diffuse  yellowish  j)igmentation,  or  iu  i^art 
showing  the  presence  of  yellow  and  brown  pigment-granules. 

A  third  portion  of  the  blood-corpuscles  disintegrates  at  the  site  of 
the  extravasation,  and  forms  yelloic  and  brotvn  granules  and  lunqys.  Tlie 
pigment-granules  and  lumps  which  arise  either  directly  from  the  disinte- 
gration of  red  blood -corpuscles,  as  well  as  the  crystals  and  granules  pre- 
cipitated from  the  dissolved  hfemogiobin,  are  often  taken  up  by  cells, 
partly  leucocytes  and  partly  cells  derived  from  proliferating  tissue;  and 
these  foi-m  the  so-called  Nood-corpuscle  cells  and  pigment-containing  cells 
(Figs.  115,  A,  and  116,  a,  h). 

At  the  beginning  of  the  disintegration  of  the  red  corpuscles  the  color- 
ing-matter present  is  htemoglobin,  but  this  cjuickly  undergoes  changes; 
and  the  yellow  and  rusty  masses  and  granules  which  are  found  both  in  the 
cells  and  lying  free,  and  which  become  changed  in  the  course  of  time  into 
darker  pigment,  are  rio  longer  lieemoglobin  itself,  but  i-ei)i-esenl  diffei-ent 
derivatives  of  hcemoglobin.  According  to  their  chemical  composition 
these  derivatives  maA'  l)e  divided  into  two  groups,  one  iron-free,  the  other 
containing  iron.  The  former  is  known  as  lueinatoidin,  the  latter  as  hamo- 
Hiderin  (Xeumann). 

Haematoidin  ( identical  with  bilirnhin)  is  a  ruby-red  (Fig.  115,  P,)  or 
reddish  yellow  (Fig.  IHJ,  b)  pigment  occuning  either  in  ciTstalli:ie  form, 
or  as  granules,  which  may  be  amorphous,  but  often  show  a  somew  hat 
angular  shape  (Fig.  116,  b),  suggesting  rudimentary  and  imperfect  crys- 
tals. Hsematoidin  is  soluble  in  chlor-oform,  carbon  disuli)hi(le,  and 
absolute  ether;  and  insoluble  in  water  and  alcohol.  It  would  appear  to 
be  formed  especially  when  haemoglobin  is  but  slightly  expose<l  to  the 
action  of  living  cells,  as  is  especially  the  case  in  the  centre  of  large  ex- 
travasates  and  in  htemorrhages  into  the  body-cavities,  as,  for  example. 


244  THE    RETROGRADE    CHAXGES. 

into  the  pelvis  of  the  kidney-  or  the  subdural  space.  It  may  be  pro- 
duced aitilicially  by  the  iutroductiou  of  glass  capsules  coutainiiig  blood 
beueath  the  skiu  or  into  the  peritoneal  ca\ity  in  such  a  way  that  the 
blood  within  the  capsules  may  be  exposed  to  the  action  of  the  tissue- 
fluids  but  not  of  the  cells. 

The  granules  and  crystals  of  hrematoidin  are  found  in  the  tissues 
either  free  (Fig.  115,  B),  or  enclosed  in  cells  (Fig.  116,  b).  In  the  lat- 
ter case  the  granules  and  crystals  are  usually  taken  up  by  phagocj'tes 
after  they  have  been  formed ;  though  occasionally  it  may  happen  that 
the  hfematoidin  while  in  solution  is  taken  up  bj"  fixed  couuective-tissue 
cells,  for  example,  cartilage  or  fat-cells,  and  then  precipitated  in  solid 
form. 

Haemosiderin,  the  derivative  of  the  red  blood-cells  which  contains, 
iron  in  demonstrable  quantity  microscopically,  is  usually  found  in  the; 
tissues  as  yellow,  orange,  and  brown  granules  and  lumps  which  become' 
darker  in  the  course  of  time.  They  are  for  the  greater  j)iirt  contained; 
within  cells,  and  in  part  are  formed  within  the  cells.  : 

When  treated  with  potassium  ferrocyauide  and  dilute  hydrochloric, 
acid  h?emosideriu  becomes  deep-blue  through  the  formation  of  Berliu| 
blue  (ferric  oxide  salt  of  hydroferrocyanic  acid)  (Fig.  116,  a).  When 
treated  with  ammonium  sulphide  there  is  formed  a  black  sulphide  ot; 
iron. 

Haemosiderin  appears  to  be  formed  particularly  (Xeumann)  when  the 
blood  in  an  extravasate  or  in  a  thrombus  is  subjected  to  the  action  ol- 
cells ;  and  it  is  consequently  seen  more  frequently  in  small  extravasate;; 
and  at  the  periphery  of  larger  ones.  The  formation  of  hoemosiderin  majj 
take  place  either  within  the  cells  or  free  in  the  tissue.  The  pigment  eui 
closed  within  cells  (sideroferous  cells)  nuiy  have  been  formed  from  th*' 


/:m 


^'^ 


Fig.  110.— Cells  containing  hfemosiderin  and  hsematoidin  from  an  old  haemorrhagic  foeus  in  the  braM 
(Alcohol,  Berlin-blue  reaction.)  a.  Cells  containinR  hi¥iiK)siderin ;  ?>.  cells  containing  haeuiatoidin ;  c,  L-i 
granule  cells  which  have  become  clear;  d,  newly  formed  connective  tissue.     X  SOU.  ' 

remains  of  disintegrated  red  blood-cells  which  have  been  taken  up  l'{ 
the  cells,  or  from  dis.solved  luemoglobiii  which  has  been  absorbed  by  ti 
cells.  In  favor  of  the  latter  mode  of  formation  is  the  diffuse  yellow  col  j 
seen  in  both  wandering  and  fixed  cells,  which  becomes  blue  when  t| 
Berlin-l)lne  reaction  is  applied.  Fnrther,  when  Imemoglobin  is  excretf 
through  tlie  kidneys,  iron-containing  ])igment-granules  form  in  the  rer 
epithelimn;   and  moreover  fixed  cells,  as  cartilage-cells,  for  exampj 


H.EM  ATOG  EXO  IS    I'lG  .M  EX  TS. 


which  could  hardly  be  supposed  to  act  as  phagocytes  and  take  uj)  fiag- 
iiionts  oi  red  cells,  often  eontaiii  uranules  of  hieniosideriii,  e\eii  when 
lying  outside  of  the  immediate  neighWoihood  of  the  exlravasate. 

The  free  pigment  and  the  pigmentetl  cells  cause  a  distinet  ])igmenta- 
tion  of  the  exti'a\asate  ;nid  its  immediate  neighborhood.  Tlie  pigmented 
cells  soon  pass  into  the  lymph-vessels  and  a  )iirf(ist<i.sis  of  the  pit/ in  cut  takes 
place,  as  a  result  of  which  the  pigment  is  found  in  the  iymph-vessels  and 
their  neighborhood,  and  in  the  lymph-glands  where  it  is  found  first  in  the 

free  cells  of  the  lymi)h- 


-C 


)^^'ti- 


■^'I®'' 


t 


w. 


h 


'M;m 


sinus  (Fig.  117  ).  Later 
it  may  be  taken  up  by 
the  tix*'d  tissue-cells.  In 
the  coui'se  of  time  the 
hicmosideriu  is  de- 
stroyed and  disai)pears. 
The  view^  which  is  held 
by  many,  that  luemosi- 
derin  is  changed  into  a 
black  melanin,  is  not 
supported  by  the  actual 
facts.  The  brownish- 
black  graiudes  in  the 
lungs,  which  luive  been 
explained  as  due  to  such 
a  change,  are  found 
through  high  magnitica- 
tion  (Xeumanu)  to  consist  of  one  or  several  minute  particles  of  carbon 
surrounded  by  a  coating  of  hfemosiderin. 

If  htemosiderin  is  brought  into  contact  with  hydrogen  sulphide  it  be- 
comes black ;  and  as  the  result  of  such  reaction  there  may  be  produced 
in  the  cadaver  black  and  green  spots  or  a  more  diffuse  discoloration, 
which  are  known  as  pseudomelanosis.  It  is  observed  most  often  in  the 
intestine,  peritoneum,  and  in  suppurating  wounds,  since  in  these  regions 
hydrogen  sulphide  is  more  likely  to  be  formed  in  the  course  of  i)ut refac- 
tion. 


Fig.  U7.— Accumulation  of  pignipnt-eontaininff  cells  In  the 
lymph-glands  after  resorption  of  an  extra vasate  of  l)loo(i.  (Miiller's 
fluid,  caruiine.)  «.  Cortical  node;  h,  lymph-sinus;  c,  cells  con- 
tainiug  pigment-granules.    X  100. 


Arnold  lias  recently  declared  that,  both  in  hfematogenous  and  exogenous  siderosis 
(see  §7l>,  the  iron-gram/les  of  the  sideroferoua  cells  (leucocytes,  connective-tissue  cells, 
liver-cells,  etc.)  are  not  iron-granules  wliich  have  been  taken  up  from  without  througli 
phagocytosis,  or  which  have  been  precipitutt-d  witliin  the  cells,  but  an-  ciianncd  ccll- 
plasmosonics  which  have  taken  up  the  iron,  converted  it,  and  combined  it  witii  them- 
selves. The  statements  made  in  the  main  text  (ii^^  70  and  71)  as  to  the  genesis  of  a  por- 
tion of  the  sideroferous  cells  harmonize  wit li  Arnold's  view,  but  it  must  be  allirmed 
that  a  formation  of  sideroferous  cells  through  phagocytosis  also  occurs,  both  in  case  of 
extravasates  and  hajmachromatoses  due  to  intravascular  destruction  of  the  red  bh^od- 
cells. 

Pseiidomelniiosis  is  not  produced,  as  man3^  authors  l)elieve,  by  the  action  of  hydro- 
gen sulphide  upon  the  blood,  but  is  formed  by  the  action  of  hydrogen  sulphide  upon 
hajmosideriu.  According  to  the  investigations  of  .?^e/Zer,  Arnold,  and  Errntt,  black  pig- 
ment may  also  be  formed  during  life,  through  the  action  of  bacteria  which  ]iro(luce 
hydrogen  sulphide  Pseudomelanosis  of  tlie  human  hiumolympli-nodes  (  Warthin)  may 
occur  in  coion-l)acillns  infections  as  the  result  of  the  action'of  II.S  in  the  blood  upon 
the  ha-raosiderin  deposited  in  the  glands  following  an  excessive  hawnolysis. 


246  THE    RETROGRADE    CHANGES. 

Literature. 

{Hcematogenous  Pigments.') 

Arnold:  Siderofere  Zellen.     Anat.  Anz.,  xvii. ;  Virch.  Arch.,  161  Bd.,  1900. 

Borst:    Melanose  des  Pericardiums  (Epithelpigmeatirung).     Virch.  Arch.,   147  Bd., 

1S9T. 
Cordua:  Ueber  den  Resorptionsmechanismus  von  Blutergilssen,  Berlin,  1877. 
Diirck:    Veranderungen   d.   Blutungen  im  Centralnervensystem.     Virch.   Arch.,   13( 

r,(l..  1892. 
Ernst:  PsL-udonielanose.     Virch.  Arch.,  153  Bd.,  1898  (Lit.). 

Gabbi:  Lc  celluk'  globulifere  nel  loro  rapporti  alia  tisiologia  del  sangue,  Firenze,  1891 
Lang-hans:  lie-sorptiou  der  Extra vasate  u.  Pigmeutbildung.     Virch.  Arch.,  49  Bdi 

1870. 
Milner  :  Pigmentbild.  inc.  cxtraduralen  Hiimatome.     Virch.  Arch.,  174  Bd.,    1903, 
Miihlmann :    Pigmeutmetamorphose  der  rothen  BliUkorpercheu.      Virch.   Arch.,   121 

Bd.,  1S91. 
Neumann,  E.;  Beitrage  zur  Kenntniss  der  pathologischen  Pigmente,  ih  ,   111  Bd.  j 

1888,  177 Bd., 1904;  Das  Pigment  der  braunen  Lungeninduration,  ib.,  161  Bd.,  1900 
Perls:  Nachwcis  von  Eisenoxj'd  in  gevvissen  Pigment  en,  ib.,  39  Bd.,  1867. 
Q,uincke:  Dent.  Arch.  f.  klin.  Med.,  25,  27,  and  33  Bd.  ; 

Schmidt:  Vcrwaudtschaft  d.  hamatogeueu  u.  autochthoneu  Pigmente.     Virch.  Arch., 

115  Bd..  1SS9;  ilainonhagie  u.  Pigmcntbilduug.  Ergebn.  d.  allg.  Path.,  iii.,  189';! 
Skrzeczka:  Ueber  Pigmcntbildung  in  Extra va.saten.  Beitr.  v.  Ziegler,  ii.,  1888. 
Virchow:  Die  pathologischen  Pigmente.  Virch.  Arch.,  1  Bd.,  1847. 
Vossius .  Griudiciie  Fiirbnng  der  Cornea  nach  Traumen.  Graefe's  Arch.,  35  Bd.,  188J' 
Warthin  :  Psendomelanosis  of  the  Hiemolymph   Glands.     Anier.  Jour,  of  3Ied.  So 

1904. 
Zeller  u.  Arnold:  Pseudomelanotische  Abscesse.     Virch.  Arch.,  139  Bd.,  1895 
Ziegler:  Uiitersiichungeu  iiber  die  Herkunft  der  Tuberkelelemente,  Wilrzburg,  187.' 

^  71.  When  large  numbers  of  red  blood=celIs  break  down  in  tb 
circulating  blood,  a  i)oition  of  the  dissolved  luTBinogiobiii  or  iiietlieeui(j 
globin  may  pass  into  the  phisuia,  or,  on  the  other  hand,  fragments  of  re 
cells  may  be  carried  about  in  the  circulation.  Such  a  destruction  of  re 
cells  occurs  to  a  marked  degree  in  poisoning  with  arsenic,  toluylendi 
niin,  potassium  chlorate,  and  morels;  to  a  lesser  degree  in  other  diseases 
such  as  many  infections,  malaria,  pernicious  antemia,  and  in  overheatin 
of  the  body.  The  passage  of 
haemoglobin  or  methtemoglobin 
into  the  blood-plasma  leads  to 
the  condition  of  hcemoglobin- 
cemia,  in  which  the  blood- 
plasma  is  colored  red.  When 
the  amount  of  dissolved  hae- 
moglobin in  the  blood  is  large, 
a  portion  may  be  excreted 
througli  tlie  kidneys,  giving 
rise  to  hwmoglohinuria  or  meth- 
ccmoglohinuria,  in  which  con- 
ditions the  urine  may  present 
a  bloody  appearance,  or  a  color 
Aiirying  from  a  clear  brownish - 
rod  to  a  dark  reddish-black. 
This  occurs  particularly  in  the 
case  of  the  first-named  poisons, 

but  also  occasionally  after  the  action  of  other  injurions  influences,  as,  f 
example,  after  exposure  to  cold  (periodical  haemoglobiuuria). 

When  formed   jyroducts    arise    from    the    disintegration   of  the  r 
cells,    as,   for  example,  after  extensive    burns,   they  collect  first  in  t 


i  ii0i>^ 


Fig.  lib.— Iiiiliii 
yellow  lipiiiosidi  1 
anaemia      (omiik 
state  of  fittv  lit^'i. 


of  the  livei-rods  w 
I  a  rase  of  pernici 
sideiiii,  /),  (ells  11 


H.F.MATOGKXOTS    T'TGMEXTS. 


capillaries  of  the  liver,  spleen,  lympb-glaiuls,  and  bone-marrow,  and  to 
a  less  extent  in  other  oigans;  and  are  sooner  or  later  taken  nj)  by  cells. 

As  the  lesnlt  of  an  increased  sni)ply  of  luenio^lobin  to  the  li\(M'  the 
funetional  activity  of  this  organ  is  increased,  so  that  the  (imount  of  hilr- 
pif/ment  hi  the  hilc  man  ^^^  much  greater  than  normal;  and  under  certain 
conditions  oxylui'nioglobin  may  appear  in  the  bile  (Stern).  Wlien  the 
blood-destruction  is  very  great,  the  liver  may  not  be  able  to  disi)osc  of 


Tig.  119.— Hfemoohromatosis  of  tbe  liver.  (Alcohol,  cannlue.)  a.  Acini;  h.  peritoneum;  c,  branches 
of  the  portal  vein ;  (Mntiltrated  periportal  connective  tissue ;  e.  pigment  lying  within  the  liver-acini ;  /, 
ceniral  veins.    X  20. 


all  the  blood-pigment  brought  to  it ;  and  in  consequence  derivatives  of 
hsmoglobin  are  deposited,  partly  in  the  liver  and  partly  in  other  organs, 
or  may  l)e  in  part  excreted  by  the  kidneys.  In  tliis  way  thci'e  may  arise 
a  more  or  less  extensive  hasmochromatosis  of  diflerent  organs,  the  cells 
of  which  show  au  ochre-yellow  or  l)rown  color. 

The  derivatives  of  haemoglobin  deposited  in  this  way  are  partly  iron- 
free  pigments  and  partly  hcemomderin  ;  but  the  latter  is  particularly  a 
frequent  cause  of  pigmentation  of  tissues,  and  it  is,  therefore,  proper  to 
speak  of  a  pigmentation  by  hasmatogenous  siderosis. 

These  deposits  of  iron-containing  pigment  are  chielly  in  the  lixcr, 
where  they  api)ear  paitly  in  the  form  of  yellow  granules  and  lunii»s, 
which  are  for  the  greater  ])art  enclosed  in  leucocyt(^s  lying  within  the 
liver-capillaries.  Further,  they  are  found  also  in  the  form  of  tine  yellow 
granules,  which  give  the  iron-reaction,  in  the  endothelial  cells  of  the 
capillaries  (to  which  the  stellate  cells  of  Kui)fl"er  belong),  and  in  the 
liver-cells  (Fig.  118,  a).  In  many  diseases,  as,  for  example,  i)ernicions 
malaria  or  pernicious  anaemia,  tlie  majority  of  the  liver-cells  contain 
such  pigment,  so  that  the  liver  througli  the  presence  of  so  much  iron 
takes  on  a  characteristic  yellowish-broMii  color. 

When  large  quantities  of  the  prodncts  of  the  disintegiati(jn  of  red 


248 


THE    RETROGRADE    CHAXGES. 


blood-cells  are  broiigbt  to  tlie  liver,  they  accumulate  particularly  in  the 
periportal  couuective  tissue  aud  in  the  periphery  of  the  acini  (Fig.  119. 
d,  e).  The  lumps  or  granules  of  iron-containing  pigment  lie  either  froe 
in  the  capillaries,  or  in  the  tissue ;  or  are  enclosed  within  leucocytes, 
liver-cells,  connective-tissue  cells,  or  the  capillary  endothelial  cells. 
The  infiltrated  area  presents  to  the  naked  eye  a  reddish -brown,  rusty 
color. 

The  iron-pigment  which  is  carried  to  the  S2)le€n  is  deposited  chietly 
in  the  pulp  within  free  cells ;  but  granules  are  also  found  in  the  fixed 
cells.  In  the  lymph-glands  the  iron  granules  are  found  chiefly  in  the  free 
cells  of  the  lymph -channels.  In  the  hone-nuurow  retained  hiemosideriu 
(Fig.  120)  is  found  partly  in  free  cells  lying  within  the  capillaries,  and 
partly  iu  the  endothelium,  also  partly  in  the  marrow-cells ;  the  number 
of  iron  containing  cells  may  be  very  marked. 

In  the  Ikhieys  the  hemosiderin  granules  are  most  abundant  in  the ; 
epithelium  of  the  convoluted  tubules  (Fig.  121,  «),  but  they  are  also; 
found  in  the  lumina  of  the  urinary"  tubules  (&),  in  the  epithelium  of  j 
Bowman's  capsule  {e),  and  in  the  endothelium  of  the  capillaries.  If' 
small  particles  of  hsemosideriu  are  present  in  the  circulating  blood,  they ' 
will  usually  be  found  in  the  kidney-vessels.  When  haemoglobin  is  ex-. 
creted  by  the  kidney,  drops  of  this  substance  will  be  seen  lying  iu  the| 
tubules.  In  cases  of  marked  deposit  of  pigment  the  kidney  may  show  a; 
distinct  pigmentation  even  to  the  naked  eye. 

The  hsemosiderin,  which  is  found  in  the  different  tissues,  has  been 
brought  to  them  in  the  form  of  small  lumps  or  granules,  and  is  containeil 
chiefly  in  leucocytes.     On  the  other  hand,  another  part  of  the  iron-gran- 


FiG.  120.— Hsemosiderin  deposit  in   the  hone-marrow  (mixed  fatty  and  lymphoid  maiTow),  in  ictei 
lAlcohol,  carmine,  Berlin-blue  reaction.)     X  300. 


ules  is  precipitated  in  solid  form  within  the  cells  from  substances  broug" 
to  them  in  solution.  Since  the  cells  (liver-cells,  kidney  epithelium,  e 
dothelium  of  the  blood- \e.ssels,  and  the  cells  of  the  lymph-glands,  bou 
marrow,  and  spleen)  not  infrequently  show  a  diffuse  blue  color  after  t ) 
iron-test  has  been  ai)i)lied,  the  iron  must  be  diffused  throughout  tliece- 
piotoplasm,  aud  is  probably  converted  later  into  the  granular  form.  ,5 
is  also  possible  that  the  diffuse  coloration  may  arise  iu  part  from  a  sol^ 


H.EMATOGEXOrS    PIGMENTS.  240 

tion  of  iron  within  the  cells.  Aocoidino-  to  the  observations  of  different 
authors  it  is  assnnied  that  besides  the  colored  dejxjsits  of  pigment,  color- 
less granules  of  an  iron-albuniiuate  maybe  present  in  ll'.r  cells.  This 
theory  is  supported  by  the  observation  that  more  ])i,i:iiicnl  .uranules  arc 
visible  after  the  iron  reaction  has  been  ap])li('(I.  Iliaii  could  be  seen 
before. 

The  deposit  of  iron=free  pigments,  hicmaloidin  or  hilinihiu  is  not  of 
freiiuent  occurrence  in  luemoclwomatosis,  l)ut  occasionally  yellow  .urau- 
ules  wliich  do  not  give  the  iron  reaction  are  found  in  the  organs  named 
alwve;  audit  may,  therefore,  be  assumed  that  the  pigment  iupait  may 
he  constantly  free  from  iron. 

]]y  the  majority  of  authors  (sec  Oei/er,  Inc.  cK.),  tlu'  mottled pif/m('iitiiti"ii  of  the  s/,iii 
■nliicli  develops  in  clirouic  arsenic  jyn'.<<o/iun/.  and  wiiicli  is  due  to  tlie  dejiosit  of  small 
yellowish-brown  pigment  granules  in  the  eoiium  and  epidermis  (similar  to  tlie  pig- 
mentation of  Addison's  disease),  is  to  be  classed  with  the  luenuicliromatoses.  It  is  to 
be  referred  to  the  degenerative  influence  of  arsenic  upon  the  bone-marrow  and  the 


FifJ.  121.— Hjematogenous  deposits  of  iron  in  tlie  kidney  in  pernicious  rnahiiia  (((intracted  in  Baga- 
mayoi.  fAlcohol,  carmine,  Berlin-lilm-  rcactiim.)  <(,  ('(invdliitcil  tiiiuilt-s,  wIkis.-  cpiiiifiial  cells  contain 
iron  yrranules  and  are  stained  diffusely  liUie;  //,  iroii-f-Miiiiuli-s  in  the  lumen  of  the  tubules;  c,  straight  tub- 
ules; (/,  glomerulus  ;  e,  epithelium  of  the  capsule,  cnutaiiiin^  irou-<:ranules.         l.")(l. 

tlood.  It  should  be  noted,  however,  tliat  the  jiigment  does  not  give  the  iron  reaction, 
and  that,  according  to  other  observations,  pigment  in  epithelium  which  is  derived  fiom 
haemoglobin  is  not  permanent:  and  that  no  increased  destruction  of  the  red  blood-cells 
occurs  in  the  affected  individuals  {Muir). 

The  organism  supplies  its  need  for  iron  through  the  assimilation  of  the  iron 
compounds  fdund  in  the  iron-containing  articles  of  food.  The  iron  coiuained  in  tlie 
iron  pre])arations  used  for  medicinal  purposes  is  absorbed  from  the  small  intestine,  in 
partieidar  from  the  duodenum.  Iron  absorbed  in  excess  is  in  part  stored  up  as  haino- 
siderin  in  the  spleen,  bone-marrow,  and  lymph-glands,  or  temporarily  in  the  liver;  and 
in  part  excreted  through  the  kidneys,  liver,  and  large  intestine. 

Ill  malaria  tin,  pifiim nts.  are  fof-med  as  a  result  of  tlie  destruction  of  the  red  cells  by 
the  malarial  iiaiasifc.  One  of  these  is  formed  by  the  malarial  i)lasmodiuin  itself,  is 
contained  within  the  parasite,  is  black,  and  gives  no  iron  reaction.  Its  nature  is  not 
known. 

The  second  pigment  is  ha?mosiderin,  which  passes  into  the  blood-plasma  as  the  re- 
sult of  the  destruction  of  the  red  blood-cells,  and  is  deposited  in  the  liver,  spleen,  and 
bone-marrow.  In  cases  of  marked  destruction  of  the  blood  tliere  may  occur  also  a  side- 
rosis^of  the  kidneys  (Fig.  131),  and  an  excretion  of  iron  in  the  urine. 

The  (jreen  color  ichich  is  observed  in  the  neidlihorhood  of  blnod-contditu'tiri  resselx  in  de- 
cadavers  is  to  be  referred  to  a  formation  of  sulphur-methtemoglobin  through 


250  THE    RETROGRADE    CHANGES. 

the  action  of  HjS  on  oxyhaemoglobin  {Hoppe-Seyler,  Earnack).     In  the  absence  of  oxy- 
gen, sulphur-bitmoglobiu  is  formed,  which  possesses  a  dark -red  color  {Earnack). 


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Afanassiew:  Toluylendiaminvergiftung.     Zeitschr.  f.  klin.  Med.,  vi. ;  Mit  Hamoglo- 

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(Lit.). 
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I 


ICTERUS.  251 

Stadelmann:  Der  Ikterus,  St'itt.irart,  tS91. 

Stern:  Ueber  das  Auftreteu  von  Oxyliiiinoglobiu  ia  der  G:ille.     Virch.  Arch.,  123  Bii... 

isi)l. 
Stiihlen:  Eiseugchalt  versch.  Orgaue  bei  Aiulmie.     Deut.  Arch.  f.  klin.  Med.,  54  Bd., 

18!)."). 
Tedeschi :  Das  Eisen  in  d.  Organen  normaler  u.  entmilzter  Thicre.    Beitr.  v.  Zicgler, 

Nxiv.,  1S9S. 
Weidenreich. :  Schicksal  d.  r.  Bhitkorperchen.     Anat.  Anz.,xxiv.,  1908. 
Wyss:  I'cbcr  Ansuniuelauose.     Correspbl.  f.  Schweizer  Aerzte,  xx.,  1890. 
Zahn:  Ueber  Piginentiiililtratiou  der  Knorpel.     Vn-ch.  Arch.,  72  B(i.,  1878. 
Zaleski:  Eisengelialt  der  Leber.     Zeitr.  f.  phys.  Chem.,  x.,   188(5;   Zur  Eisenfrage. 

Virch.  Arch.,  104  Bd.,  188G;  Ausscheidung  des  Eisens.     Arch.  f.  exp.  Path.,  xxiii., 

1887. 

§  72.  Icterus  or  jaundice  is  a  pathological  pigmeutation  of  the  tissues 
due  to  the  preseuce  of  bile-pigment.  Icterus  is  a  symptom  which  occur.s 
in  tlie  course  of  numerous  diseases  of  the  liver,  and  is  of  frequent  occur- 
rence even  in  the  first  days  of  life  {icterus  neonatorum). 

The  pathological  pigmentation  which  characterizes  icterus  is  axiparent 
during  life,  particuUirly  in  the  skin,  conjunctiva,  and  in  the  urine;  in 
the  cadaver  the  internal  organs — the  serous  membranes,  lungs,  kidneys, 
liver,  the  subcutaneous  and  intermuscular  tissues,  the  blood-plasma, 
clots  lying  in  the  vessels,  etc. — may  show  an  icteric  coloi-ation.  In 
recent  cases  the  icteric  color  is  yellow;  in  long-standing  cases  the  skin 
takes  on  an  olive-green  or  dirty  grayish-green  color,  while  similar  color- 

-x,   -^-^^  i^pMxc^    ^^:.--^:^  •^-•v:* 


t 


pc: ..  j»5^^«kJil. 


•"\>^.-:.*>^-:.cS<'.4:i:>.i'         ^;^'Mi"^      ^ ...sD  ^ 

Fig.  122.— obstnictive  icterus  of  the  liver,  due  to  fompn'ssion  of  the  (iiidiis  clioleilochiis  liy  a  cancer 

of  the  pall-hladder.     (Sublimate,  aluin-cariiiine.)     <f,  Iiitra-aciii.Mis  hilr-.ai.illari.'s,  i Iciat.-ly  dilateil  and 

tilled  with  bile;  /*,  widely  dilated  intra-acinous  bile-capillary,  cniitainiiitr  lart,n-  mass  of  pitriiniii  ;  c,  bilc- 
pigmenl  in  the  liver-cells  d,  t(,,  endothelium  stained  with  bile-pij,'iiit'nt ;  c.  dc.si)uaniatcd  cnddtbclium 
stained  with  bile-pif,'ment ;  /,  pifi^ment  mass  surrounded  by  cells;  (/,  rupture  of  the  pigment  contained  in  a 
bile-capillary  into  a  blood-capillary,  with  bile-stained  cells  In  th(!  neighborhood.      X  *i5. 

ations  occur  in  the  internal  organs,  particularly  in  the  liver,  and  occa- 
sionally in  the  kidneys. 

Icterus  results  from  the  entrance  of  bile — that  is,  of  bile-pir/ment  (bih'ruh'n) 

-into  the  blood  and  fluids  of  the  bod]/.     During  such  a  condition  the  urine 

excreted  contains  elements  of  the  bile,  particularly  the  bile  pigments. 


252  THE    RETKOGRADE    CHANGES. 

Icterus  is  a  hepaiogenons  disease,  inasmuch  as  the  bile-pigments  have  their 
source  iu  the  liver.  As  the  result  of  disease  processes  in  the  biliary- 
passages  or  in  the  liver  itself  the  normal  oiittiow  of  the  bile  is  liindered, 
and  the  bile  is  then  taken  up  into  the  lymphatics  and  blood-vessels  of 
the  liver.  Such  a  damming  back  of  the  bile  may  be  caused,  for  exam- 
ple, by  a  narrowing  or  closure  of  the  large  bile-ducts  through  the  forma- 
tion of  scar-tissue,  through  gall-stones  wedged  iu  the  lumen,  or  through 
tumors  developing  in  the  bile-ducts  themselves,  or  arising  outside  of  the 
ducts  and  compressing  them;  or  through  inflammatory  processes,  ab- 
scesses, connective-tissue  growths,  or  tumors  of  the  liver  which  compress 
or  pull  upon,  or  comj)letely  obliterate  the  smaller  bile-ducts,  and  iu  this 
way  hinder  the  outflow  of  blood  from  the  smaller  bile-ducts  and  capil- 
laries. 

In  the  case  of  a  stasis  of  bile  within  the  liver-lobules  the  iutercellulai- 
bile-cupillaries  first  become  dilated  and  may  become  filled  with  large  bile- 
thrombi  (Fig.  122,  a,  b).  The  dilatation  affects  also  the  blind  side 
branches  extending  toward  the  capillaries,  and  these  finally  may  be 
broken  through,  leading  to  a  separation  of  the  liver-cells  (Fig.  122,  g  i, 
also  to  cell  necrosis,  so  that  the  bile  eventually  gains  entrance  into  the 
perivascular  lymph-channels  and  thence  also  directly  into  the  blood. 
Further,  the  bile-pigment  is  heaped  up  in  granules  within  the  liver-cells 
themselves  (c),  and  the  endothelium  of  the  blood-capillaries  (d,  d^,  e  \ 
also  becomes  stained  with  bile. 

Since  there  occurs  in  the  liver-cells  a  double  secretion,  an  externalii 
one  through  the  bile-ducts  of  bile-acids  and  bile-pigment,  and  an  internal' 
one  into  the  blood-vessels  of  sugar  and  urea,  it  appears  reasonable  that  a 
passage  of  bile  into  the  blood  may  occur  not  only  through  stasis  of  the 
bile,  but  also  as  the  result  of  pathological  conditions  of  the  liver-cells  due< 
to  infections  and  intoxications.  We  may  therefore  distinguish,  in  addition' 
to  icterus  due  to  bite  stasis  or  stasis  parapedesis  (^Minkowski),  other  forms 
of  icterus  due  to  toxic  and  infectious  parapedesis  of  the  bite  (parachotia,  Pick) 
and  there  are  probably  many  forms  of  icterus  formerly  referred  to  a^ 
catarrh  of  the  bile-passages  that  may  be  explained  in  this  way. 

It  is  also  possible  that  disturbances  of  innervation  and  of  the  circula 
tion  of  the  liver  may  be  sufficient  to  bring  about  an  escape  of  bile  intc 
the  intra-acinous  lymph-channels  or  into  the  blood,  so  that  a  nervous 
parachotia  may  also  be  distinguished. 

When  bile-pigment,  either  in  solution  or  iu  the  form  of  granules  anc 
lumps,  obtains  entrance  to  the  blood,  the  tissues  of  the  bodij  become  grad- 
uitUij  permeated  with  bile-stained  lymph,  and  thereby  acquire  an  icterir 
coloi".  If  phagocytes  containing  granules  or  lumps  of  bilirubin  ar' 
present  in  the  circulating  blood,  they  may  accumulate  here  and  there 
particularly  in  the  spleen  and  the  bone-marrow.  After  a  time  th 
bile-pigment  held  iu  solution  within  the  tissue-lymph  may  become  pre 
cipitated  as  solid  particles  of  bile-pifpnent,  chiefly  in  a  granular  form,  bn, 
i-arely  in  a  crystalline  (the  latter  form  occurs  almost  entirely  in  th 
new-born,  in  whicli  the  crystals  are  found  in  the  fixed  and  wanderin 
cells  of  tlie  connective  tissue,  in  the  liver-cells,  and  in  the  renal  epith( 
linm).  The  crystals  are  in  the  form  of  rhombic  plates  and  needier 
similar  to  those  of  ha-matoidin  (Fig.  115).  In  severe  cases  of  icteri 
very  many  of  the  tissue-cells  contain  pigment,  and,  as  a  result  of  th 
metastasis  of  cells  containing  pigment,  accumulations  of  the  latter  in  th 
lymph-glands  may  occur.  ^ 

In  the  kidneys  in  which  bile-pigment  is  being  excreted  there  likewif 


ICTERUS. 


25:1 


ofcurs  ail  excretory  pigmentation,  particnlarly  of  (lie  ei^illielinin  of  jlio 
urinary  tnbules  (Fig.  12;>,  a,  d),  wjiich  in  eonsecinence  may  become 
(lesqnamated.  If,  as  tlie  result  of  the  damage  done  I0  the  secreting  cells 
through  the  excretion  of  the  bile-pigment,  Ihere  are  fornuHl,  as  is  usually 
the  case,  hyaline  casts — that  is,  hyaline  coagula  in  the  aibumin-contain- 
iug  urine  iu  the  tubules — these  likewise  become  colored  by  the  bile-i)ig- 
nient  (Fig.  12,3,  h,  c). 

Associated  with  the  deposits  of  bilirubin  in  icterus  there  is  always  a 
depoait  of  Jncmosidcrin  which  may  become  so  abundant,  ])articnlarly  in  the 
bone-marrow  (Fig.  120),  spleen,  and  lymph-glands,  and  occasionally  also 
in  the  liver,  that  the  pigmentation  of  the  organs  named  is  dependent  in 
part  upon  irou-pigmeut. 


Tig.  123. -Icterus  of  the  kidney  in  obstructive  jaundice.  (Sublimate,  carmine.)  a.  Tubular  epi- 
Uielium  containiug  yellowisti-brown  granules  ;  /»,  large  casts  stained  yellowish-green  ;  c,  cast  containing 
pigmented  oells  ;  (I,  desquamated  epithelium  containing  bile-pigment  granules.     X  201). 


When  an  increased  destruction  of  red  Uood-celh  takes  i)lace  within  the 

blood-vessels,  haematoidiu  or  bilirubin,  in  addition  to  iKemosiderin,  is 

formed  indifferent  parts  of  the  body  (see  §  71);  but  the  formation  of 

\   l)ilirul)iii  outside  of  the  liver  is  very  slight  and  is  not  suflicieiit  to  cause 

,   any  extensive  icteric  coloration  of  the  tissue,  so  that  a  purc/i/  li(rnt(fli>f/r- 

\    nomjuuiidicc  does  not  occur.     The  liver  is  the  great  elaborator  of  bilirubin, 

.;   and  in  cases  of  increased  destruction  of  the  blood-cells  the  liver-function 

j    is  increased  and  there  is  an  increased  production  and  excretion  of  bile- 

j    pigment.     An  icterus  due  to  increased  destruction  of  hJood-ccUs  can  occur 

ouly  when  at  the  same  time  there  are  present  in  the  liver  such  changes 

as  cau.se  ix  passage  of  the  bile  into  the  blood. 

[  The  (luestion  as  to  whetlier  there  is  a  liacmatoffcnous  as  well  as  a  liepato^';enoiis 

I    jaundice  lias  long  been  an  object  of  discussion,  and  remains  unsettled  at  the  i>resent 
I    time,  in  spite  of  numerous  experimental  investigations  directed  toward  its  solution. 
Since,  as  a  matter  of  fact,  bilirubin  may  be  formed  in  the  most  dilTerent  kinds  of  tissue 
from  extravasated  blood,  the  occurrence  of  a  lia'iiiatogenous  icierus  would  a  jirion  n])- 
\     pear  very  probable.     Experimental  investigations  as  to  the  results  of  the  destruction  of 


254  THE    RETROGRADE    CHANGES. 

red  cells  in  the  circulating  blood,  particularly  through  the  action  of  arsenic,  tnluylen. 
diamin,  and  potassium  chlorate,  have  shown  that  the  derivatives  of  blood-pigment 
which  are  formed  in  the  tissues  and  there  retained  for  a  long  time  are  essentially  iron- 
containing  pigments  (hoemosiderin),  while  the  production  of  bilirubin  is  practically  con- 
fined to  tiie  liver,  which  for  the  time  being  secretes  an  increased  amount  of  richly  pig- 
mented bile. 

According  to  the  investigations  of  J/««^wrsA-i  and  JVaunyn,  the  urine  of  geese  and 
ducks  after  removal  of  the  liver  contains  no  bile-pigmenl — a  fact  which  would  indicate: 
that  the  transformation  of  blood-pigment  into  bile-pigment  is  ordinarily  coulined  to  the! 
liver.  The  inhalation  of  arseniureted  hydrogen  for  a  few  minutes  is  sufficient  to  produce; 
in  geese  in  a  very  short  time  an  intense  polycholia  and  hamiaturia,  the  urine  containing 
ha-moglobin  in  solution,  disintegrating  red  cells  and  biliverdin.  If  the  liver  from  suclii 
a  goose  be  removed,  the  biliverdin  quickly  disappears  from  the  urine,  and  no  trace  of- 
bile-pigment  can  be  demonstrated  in  the  blood.  It  is  tlierefore  evident  that  in  arsenict 
poisoning  the  formation  of  the  bile-pigment  is  confined  to  the  liver,  in  which  organs 
leucocytes  enclosing  iron-containing  fragments  of  broken-down  red  cells  are  found  tci 
be  present.  i 

In  so  far  as  it  is  possible  to  judge  from  the  experimental  investigations  which  havej 
been  made  up  to  the  present  time,  a  pure  htematogenous  jaundice  does  not  appear  tci 
occur.  The  mere  fact  of  the  occurrence  of  jaundice  after  intoxications,  inhalation  oi! 
ether  and  chloroform,  transfusion  of  blood,  snake-bite,  septicaemia,  typhoid  fever,  yel- 
low fever,  paroxysmal  haemoglobinuria,  etc.,  cannot  be  taken  as  proof  of  the  existence 
of  a  hematogenous  jaundice.  There  is,  indeed,  in  these  conditions  an  increased  destruc-j 
tion  of  red  blood-cells;  but  bilirubin  is  essentially  a  product  of  the  liver,  and  if  jaundicfi 
occurs  it  can  be  due  only  to  the  fact  tliat  a  portion  of  the  bile-pigment,  which  is  proj 
duced  in  excess,  has  found  its  way  into  the  blood.  J 

According  to  von  Kupffer  and  Pfeiffer,  the  bile-capillaries  terminate  in  intracellulaij 
secretorv  vacuoles;  from  these,  according  to  Nauu-erck,  Stroebe,  and  Brou-icz,  dcVicnU 
intracellular  secretory  canaliculi  are  given  olf,  forming  a  network  around  the  nucleus; 
According  to  Nauwcrck,  the  internal  secretion  of  the  liver  also  takes  place  into  ver^j 
delicate  intracelhilar  canaliculi.  Schci/er  describes  small  nutritive  canaliculi  withii 
the  liver-cell  communicating  with  the  blood-capillaries.  Arnold  opposes  the  viev! 
that  any  preformed  sy.stem  of  canals  exists  within  the  liver  cells. 

In  the  icterus  occurring  so  frequentlj^  in  the  new-born  (Schmorl)  there  occurs  hot/ 
a  difl'use  and  a  scattered  yellowish  coloration  of  the  brain  limited  to  the  neighborhood 
of  the  nuclei,  while  in  later  life  the  brain,  even  after  a  long-continued  icterus,  remain 
free  from  pigment.  With  the  nuclear  icterus  there  are  also  found  ganglion-cellj 
stained  with  bile.  j 

Literature. 

(Icferus.) 

Abramow  u.  Samoilowicz:  Pathogenese  d.  Ikterus.     Virch.  Arch.,  176  Bd..  1904.    I 
Arnold:  Feincre  .Struktur  der  Leberzellen.     Virch.  Arch.,  166  Bd.,  1901. 
Auld:  H;ematogenous  Jaundice.     Brit.  Med.  Journ.,  i.,  1896. 
Birch-Hirschfeld:  Die  Entstehung  der  Gelbsucht  neugebor.   Kinder.    Virch.  Arch^ 

S7  Bd.,  18S2. 
Browicz:   Intracelluliire  Gallengange,  etc.     Deut.  med.  Woch.,   1897;    Chi.   f.  all;' 

Path..  1898;  Lebercapillaren.     Bull,  de  I'Ac.  des  sc.  de  Cracovie,  1900. 
Biirker:  Ort   d.  Resorption  d.  Galle.     A.  f.  Phys.,  83  Bd.,  1901. 
Dastre  ct  Florescvi:  Pigments  liiliaires.     Arch',  de  phys.,  ix.,  1897. 
Epping-er,  H. :   Pathogenese  des  Ikterus.     B.  v.  Ziegler,  xxxi.,  1902,  und  xxxiii..  190 
Halter  u.  Lauterbacher:  Resorptionsikterusbeim  Frosch.   Beitr.  v.  Ziegler,  x.,  189 
Harley :  Pathology  of  Obstructive  Jaundice.     Brit.  Med.  Journ.,  1892;  Leber  u.  Gal; 

\\;ihrenddauernden  VerschlussesvonGallen-undBrustgang.    Du  Bois-Reymond' 

Arel...   1893.  I, 

Hofnieier:  Die  Gelh.sucht  der  Neugeborenen.  Zeitschr.  f.  Gebh.  u.  Gvn.,  viii.,  ISSJm 
Ivannovics:  Kxp.  Tenters,  lib.  Ikterus.     Z.  f.  Heilk.,  25  Bd.,  1904.      "  ] 

Kiener  ct  Engel:  Pathogenie  de  I'ictere  et  ses  rapports  avec  I'urobilinurie.     Arch.  0,^ 

phvs..  X..  1887. 
Kuukel:  Teller  fins  Auftreten  verschiedener  Farbstoffe  im  Harn.     lb..  79  Bd..  188^ 
Lesage  ct  Demelin:  L'ictoredu  nouveau-ne.     Rev.  denied.,  1898. 
Lowit;  Bil.iim-j:  des  Gallenfarbstoffs  in  d.  Froschleber.     Beitr.  v.  Ziegler,  iv..  1889.  ' 
Minkowski:   Die  Storungen  der  Leberf unction.     Ergebn.  d.  allg.  Path.,  Jahrg.  i' 

1897. 


I 


EXTRINSIC    PIGMENTS.  25") 

Minkowski  u.  Naunyn:  Pathologie  d.  Leiior   u.  d.  Tktoru.s.     Arch.   f.   oxp.  T^itli., 

xxi..   1SS(). 
Nauwerck:  i-ehcrzelk'n  ii.  C.elbsucht.     Miiiich.  luod.  Woch.,  1S!»7. 
Neumann:   Ahscheidiuii!;  von   BilirubiiikrystalhMi   aus  d(>in    Hlulo  in   don  (Icwclx'ii. 

Arcli.  d.  Ileilk.,  viii.,  l.SGT;   Bilirubiiikiy.stalle  iin  Blutc  dcr  Noiijioliori'iicii  u.  todt- 

faulerFriichte.     lb.,  ix.,  ISGS;  ib..xvii.,  187(1;   Ikferusiiooiiatoriiin.    N'ircli.  Arch., 

114  Bd.,  1888. 
Orth:  Ueb.  d.  Vorkomnien  v.  Bilinibinkrystallcnbei  noiifid).  Kiiid<Mn.     Aircli.  Arcli., 

(•.:^Bd.,  1875. 
Pick:  Eiitstohung  d.  Iktenis.     Wien.  khii.  Woch.,  1894;    Wesoii  d.  Ikt.      Pnajr.  iiicd. 

Woch..  1895. 
Guincke:  Beitrage  zur  Lehre  voin  Ikterus.     Vircli.  Arcli.,  95  Bd.,  1884;    l'el)or  die 

Jjitstohuns;  der  Gelbsucht  Neugeborener.     Arch.  f.  exp.  Path.,  xix.,  188."). 
Roger:  Pliysiol.  norm,  et  pathol.  du  foie,  Paris,  189.3. 
Runge:  Die  Krankheitcn  iler  orsten  Lolienstage,  Stuttgart,  1893. 
Schafer:   Nutritive  Channels  within  the  Liver  Cells.     Anat.  Anz.,  xxi..  1902. 
Schmorl:    Ikterus  neonatorum.    Verb.  d.  D.  path.  Gcs.,  vi.,  1904. 
Silbermann:  Die  Geihsuclit  der  Neugeborenen.     Arch.  f.  Kinderheilk.,  viii.,  1887. 
Stadelmann:  Der  Iktenis.  Stuttgart,  1891. 
Stern:   Uel)erdie  norm.  Bildungsstatte  desGallenfarbstoffs.     Arch.  f.  exp.  Path.,  xix., 

1S8.-). 
Szubinski:  Structur  der  Leberzellen.     Beitr.  v.  Ziegler,  xxvi.,  1899. 
Wertheimer  e*, "Lepage:  Absorption  des  pigmentes dans  le  foie.     Arch,  ile  phys.,  1897. 

§  7;>.  Pigmentation  of  the  tissues  through  substances  introduced 
into  the  body  from  without  occurs  when  substances  possessing-  a  coU)r 
of  tlit'ir  o\vn  gain  entiance  in  some  manner  to  the  tissues,  where  they  are 
able  to  remain  for  some  time  without  suffering  changes.  The  mnnber  of 
such  substances  is  large,  and  the  manner  of  entrance  varied.  Tlie  most 
common  avenues  of  entrance  are  the  lungs,  wounds,  an<l  intestinal  tract.     The 


mWw 


-Deposit  of  cinaabar  ia  tattooed  skin.     (Alcohol,  alum  caniiiue.)    a.  Epithelium  ;  h,  corium; 
c,  cinnabar.    X  80. 


I  most  familiar  pigmentation  through  wounds  is  tattooing  of  t tie  sl'in,  which 

j  is  fre(iiiently  practised  by  individuals  of  civilized  as  well  as  of  uncivil- 

;  ized  nations. 

I         Tlie  method  of  tattooing  colored  figures,  etc.,  consists  inliic  iiitr(»- 

,  ductioii  of  insohdjle  granular  i)igm(Mils,  such  as  carbon,  india-iiik,  ciii- 

1  nabar,  sei)ia,  burnt  sienna,  nltiamarine,  cliioniatcof  lead,  elc.,  inloslight 

\  wouiuls  of  the  skin.     The  pigments  ai-e  iubl>ed  into  tlie  wounds,  wiiciice 

^  they  penetrate  and    intiltiate    tint   tissue  in  their  immediate  neighbor- 
hood.    A  portion  of  the  pigment  it'inains  in  Ww  corinni  (Fig.   ll!4,  c)  : 


256 


THE    RETROGRADE    CHANGES. 


another  portion  is  carried  to  the  lymph-glauds,  ^vhich  thereby  become 
pigmented. 

The  lungs  and  their  lympli-glands  may  become  intensely  pigmented 
through  the  inhalation  of  colored  dust,  sucli  as  coal-dust,  soot,  iron-dust, 
etc.  Through  the  inhalation  of  coal-dust  the  lungs  may  become  wholly 
black. 

When  coal-dust  is  taken  into  the  lungs  in  the  respired  air  a  portion 
of  the  pigment  is  carried  to  the  peribronchial  lymph-glands,  which  in 
consequence  may  become  black.  When  the  deposit  is  very  abundant 
the  lymph -glands  may  undergo  softening  and  give  off  the  pigment  into  the 
lymph-stream.      If    the     glands    are 

situated  in   the   neighborhood   of    a  ^  ^  , 

vein,  the  pigment-deposit  and  the 
softening  may  involve  the  vein- 
wall,  so  that  finally  particles  of 
coal-dust  may  pass  into  the  blood- 
stream, and  be  carried  to  other  or- 
gans, the  si^leen,  liver,  and  bone- 
marrow  (see  §  21). 

From  the  intestine  only  soluble  sub- 
stances are  absorbed,  and  a  perma- 
nent pigmentation  can  therefore  oc- 
cur, only  when  these  are  precipitated 
in  the  tissue  in  a  solid  form,  which 
is  at  the  same  time  either  black  or 
possessing  some  color.  The  most  fre- 
quent of  such  pigmentations  is  that 
known  as  arr/j/ria,  w4iich  is  due  to  the 
long-continued  use  of  silver-prepara- 
tions. In  this  condition  the  skin  may 
show  an  intense  grayish-brown  discol- 
oration, and  the  internal  organs  may 
also  present  more  or  less  pigmenta- 
tion. The  silver  is  deposited  in  the 
ground-substance  of  the  tissues  in  the 
form  of  fine  granules,  more  especially 
in  tiu;  glomeruli,  and  the  connective 
tissue  of  the  medullary  pyramids  (Fig. 
125,  b),  the  intima  of  the  great  ves- 
sels, adventitia  of  the  smaller  ones,  in  ' 
the  neighborhood  of  the  mucous  glands,  the  papilke  of  the  skin,  con 
nective  tissue  of  the  intestinal  villi,  and  in  the  choroid  plexus  of  th(i 
latei-al  ventricles.  Deposits  may  occur  also  in  the  serous  membranes,  bui 
tlie  epithelial  tissues,  the  brain,  and  the  cerebral  vessels  escape.  Exten' 
sive  deposits  of  silver  pigment  in  the  medullary  i)ortion  of  the  kidney 
may  lead  to  the  foi-mation  of  hyaline  connective  tissue,  which  ma;, 
undeigo  calcification. 

Under  especial  conditions  iron,  when  taken  into  the  body  in  excessiv 
amounts,  may  be  deposited  in  the  bone-marrow,  spleen,  and  lympli 
glands;  but  the  ])igmentation  thus  produced  is  only  rarely  visible  to  tli 
naked  eye.  In  had-poisoninfi  there  maybe  seen  a  grayish-black  discoloi 
at  ion  of  the  gums,  wliich  is  due  to  the  deposit  of  granules  of  sulphide  c 
lead  in  the  connective  tissue  of  the  mucous  membrane.  They  are  pre 
duced  through  the  action  of  liydrogen  sulphide  upon  the  lead,  which  i 
present  in  solution  in  the  mucous  membrane. 


Fig.  135.— Deposits  of  silver  In  the  pyramidal} 
portion  of  a  rabbit's  liidney,  after  seven  months'; 
arlininistration  of  silver  salts  (experiment  by  von 
K:ililili'ii.)  (Alcohol,  haamatoxylin.)  a,  Epithe-| 
liiiiii  (if  till'  <ollectinK  tubes;  b,  connective  tissiu 
witli  bniwn  silver  granules.    X  500.  ' 


tmp:  PATii()i.(xnc.\L  ahsexck  of  im(;.me.\t 


Literature. 


(A  >•(/>/)•!<(.) 


Behrend:  Argyrie.     Eulouburg's  Realencyklopiidic,  1894. 

Frommann:  Ein  Fall  von  Argyria.     Virch.  Aic;h.,  17  IJd.,  ISnO. 

Jacobi:  Aufiiahnic  der  Silberprilparate  in  dvn  Orgaiiismiis.     Arch.  f.  t'xp.  Path.,  viii 

is:s. 

Jahn:  Aiuyiic     Beitr.  v.  Ziegler,  xvi.,  1894. 

V.  Kahlden:  Altlagciuiig  dcs  Silbers  in  den  Niorcn.     Beilr.  v.  ZicultT,  xv.,  1S94. 

Robert:  Uiber  Argyric  u.  Sidcnisis.     Arch.  1'.  Derm..  2.")  Bd.,  \Hm. 

Levin:  I'cbcr  locale  Gcwclx'-.Vrgyric.     Berlin,  klin.  Woch.,  188(5. 

Riemer:  Ein  Fall  von  Argyrie.  ""Arch.  d.  Ilcilk.,  Ifi  Bd.,  is?."). 

Ruge:  Ucber  den  Bleisaum.     Dent.  Arch.  f.  klin.  3[ed.,  58  Bd.,  1898. 

Warthin:  Argvria.     Kef.  flandb.  of  Med.  Sc,  1901. 


XV.  The  Pathological  Absence  of  Pigment. 


4,   The  absence  of  pigment 


t;il  condition,  and  i.^ 


in  the  tiist  ])hu'e,  as  a  con^eni- 


Fio.  126.— Vitiligo  enderaica  (after  a  photo- 
graph received  from  Professor  Munch.) 

17 


tlien  termed  albinism  or  leucopathia  congenita. 

In  a  part  of  sneh  cases  the  absence  of 
pigment  extends  over  the  entire  body 
(alhinismus  universalis,  Kakerlaken,  albi- 
nos) ;  in  other  cases  it  is  restricted  to  cer- 
tain portions  of  the  skin  {(ilhinismits  par- 
tialis). In  tho.se  parts  of  the  skin  wiiich 
are  destitute  of  jjigmenttlie  hairs  likewi.se 
may  contain  no  pigment,  and  appear 
white  or  yellowish-white  { poliosis  ov  Uu- 
cotrichia  congenita  universalis,  et  circum- 
scrij)ta).  In  universal  alV)inism  the  pig- 
ment of  the  retina,  choroid,  and  iris  may 
also  be  wanting,  so  that  consecinently  the 
choroid,  from  the  amount  of  blood  which 
it  contain.s,  appears  red,  and  the  iri.s,  ac- 
cording to  the  angle  of  observation  and 
the  degree  of  illujiiination,  will  ai)pear 
either  blui.sh- white  or  red.  On  micro- 
scopical examination  no  pigmented  cells 
can  be  found, 

A  second  foim  of  absence  of  pigment 
is  that  condition  which  is  known  as  vitil- 
igo or  leucopathia  acquisita.  This  <tc- 
eurs  later  in  life,  either  as  a  .secinela  to 
certain  well-known  disea.ses  (scarlet  fever, 
typhus,  recuii-ent  fever),  or  as  a  symptom 
of  an  ei)idemic  disease  of  unknown  «'ti- 
ology  (vitiligo  endemica),  or  finally  with- 
out any  i-ecogni/ablc  canse.  The  forma- 
tion of  white  s])nls,  within  which  tlu-  hairs 
are  also  white  (Ictirotricliia  acipdsita  cir- 
cmnsrripta),  takes  place  n.snally  .symmet- 
rically, and  may  extend  o\er  the  greatei- 
part  "of  the  body  (Fig.  r2<i).     The  white 


258  THE    RETROGRADE    CHANGES. 

areas  are  siirrouuded  by  a  border  of  more  deeply  pigmented  skin ;   and  I 
this  suggests  that  with  the  disappearance  of  the  pigment  at  one  point  the 
pigment  is  transferred  to  adjacent  parts.     Tlie  loss  of  color  in  the  hairs 
(even  as  in  old  age)  begins  always  in  the  root,  no  more  j)igmeut  being 
transferred  from  the  hair-papilla  to  the  hair-bulb.     Finally  the  pigment-  i 
cells  of  the  papilla  disappear  altogether.  i 

A  third  form  of  loss  of  pigment  is  associated  with  traumatic  or  infec-  j 
tious  inflammations  of  the  skin,  particularly  in  syphilitic  exanthemata  ' 
and  in  leprosy ;  this  condition  is  known  as  leucoderma. 

In  scars  of  the  skin  which  remain  white,  the  newly  formed  tissue  ' 
replacing  the  defect  does  not  ]30ssess  the  power  of  producing  pigment; 
and  consequently  rei)resents  a  colorless  cicatrix  covered  by  ei^ithelium. 
Not  infrequently  such  a  scar  may  be  surrounded  by  a  pigmented  border.  : 
In  mild  forms  of  inflammation,  in  which  the  tissue  of  the  skin  suffers  jig 
loss  (syphilis),  the  disappearance  of  color  may  immediately  follow  the  j 
inflammation,  or  not  until  later,  in  which  case  there  may  occasionally  j 
occur  a  preceding  stage  of  increased  j)ignientatiou.     According  to  Ehr- ' 
maun  the  lack  of  pigment  in  such  cases  is  to  be  explained  either  by  the! 
fact  that  no  chromatophores  are  present  in  the  coriuni  to  furnish  pigment! 
to  the  eijithelium,  or  the  changed  epithelium  is  not  able  to  take  up  the! 
pigment  from  the  latter  when  present.     The  pigment  which  still  remains' 
in  the  cutis  may  then  be  absorbed.  , 

! 
According  to  Miinch,  vitiligo  is  of  common  occurrence  in  Turkestan,  and  is  consid-j 
ered  by  the  natives  (Sarts)  to  be  contagious,  so  that  they  isolate  the  individuals  affected^ 
with  this  disease  and  couiiue  them  with  lepers  in  enclosed  courts.  It  is  probable  that! 
in  the  literature  vitiligo  endemica  has  been  many  times  mistaken  for  lepra  maculosa, 
and  has  been  described  under  the  designation  "  white  leprosy  of  the  Jews. "  ! 

Literature. 

{Absence  of  Figment. )  '■ 

Behrend:  Canities  (Poliosis).     Eulenburg's  Realencyklop.,  1894  (Lit.). 
Beigel;  Beitr.  z.  Gesch.  d.  Albinismus  part.  u.  d.  Vitiligo,  Dresden,  1864. 
Ehrmann:  riautentfilrbuug  durcli  syph.  Exantheme.     Arch.  f.  Derm.,  Ergzh.,  1891,: 
Jadassohn:  Hautentfilrbung.     Vierteljahrsschr.   f.  Derm.,   1880;   Pigmentverscmejf 
pung.     Arch.  f.  Derm.,  1892.  ' 

Landois:  Plotzliches  Ergrauen  der  Haupthaare.     Virch.  Arch.,  35  Bd.,  1866.  I 

Marc:  Pathogenese  der  Vitiligo.     Virch.  Arch.,  136  Bd.,  1894.  '. 

Miinch:  Lepra  u.  Vitiligo  im  Sliden  Russlands,  Kiew,  1884-86.  ' 

Worris  :  An  Extensive  Case  of  Vitiligo.     Univ.  of  Penn.  Med.  Bull.,  1902.  I 

Schmorl:  Pigment verschleppung.     Cbl.  f.  allg.  Path.,  v.,  1894. 

XVI.  The  Formation  of  Cysts. 

§  75.  A  cyst  is  a  circumscribed  cavity  which  is  shut  off  from  the  su 
rounding  tissues  by  a  connective-tissue  membrane  or  by  tissue  of  a  mo 
complex  structure,  and  possessing  contents  difl'ering  in  nature  from  tl 
capsule.  Cysts  may  occur  in  any  tissue.  AMien  composed  of  l)ut  a  si 
gle  cliamber,  the  cyst  is  called  a  si  in  pie  ei/st :  m  Ikmi  divided  into  a  numb 
of  coMi])aitnienls,  it  is  known  as  a  imiltilocniar  ci/st. 

The  most  common  form  is  the  so-called  retention=cyst,  u-hieh  arit^ 
from  the  accumulation  of  secretions  in  preexisting  spaces  which  are  lined  u 
epithelium  or  endotheliwn. 

In   glands    provided    with    an    open    duct,   retention-cysts  will 
formed  as  the  result  of  the  obstruction  of  the  duct,  provided  that  active^ 


CYST-FOHMATIO.V. 


2o«) 


secreting  epithelium  still  exists  behind  the  point  of  obstrnetion.     Such 
cysts  are  of  frequent  occurrence  in  the  sehaceous  glands,  liair-follieU's, 

uterine  glands,  mucous  glands  of  the 
intestinal  tract,  tubules  of  the  e])idi- 
dymis  (Fig.  127,  c),  urinary  tubuh-s; 
less  frequent  in  the  biliary  passagei>, 
in  tlie  breast,  pancicas  (Fig.*  12S.  />  i.  in 
the  glands  of  the  month,  etc.  Larger 
open  canals,  sucli  as  the  uivters,  vermi- 
form apixMidix,  and  tubes  (Fig.  120,  r), 
may  also  undergo  cystic;  dilatation  as  the 
result  of  the  collection  of  secretions. 
The  obstruction  of  a  given  duct  may 
be  due  to  accumulation  of  secretion,  to 
the  formation  of  adhesions  (Fig.  129,  e), 
cicatricial  ol)literation,  compiession,  or 
constriction  of  its  lumen. 
^\^  /  Closed  glandular  cavities  and  tubes, 

^.  .'  such  as  the  follicles  of  the  thyroid  and 

the  glandular  tubes  of  the  parovarium, 
may  also  become  cystic  wlien  tlieir  walls 
produce  an  abnormal  amount  of  secre- 
tion. Likewise,  the  remains  of  fetal 
passages  and  clefts,  as,  for  exam])le,  re- 
urachus,   ^Miiller's  ducts,    etc.,  may  also 


Fig.  127.— Section  of  the  testicle  and 
epididymis,  with  multiple  cvsts  in  the  head 
of  the  epididymis,  o.  Testis;  h,  epididy- 
mis; c,  multilocular  cysts.  Slightly  reduced. 


!  mains  of  the  branchial  clefts, 
[  become  cystic. 

Small  cysts,  such  as  those  developing  in  mucous  glands,  \avy  in  size 
,  from  a  millet  seed  to  that  of  a  pea.     Larger  cysts,  such  as  occur  iu  the 

liver  and  ovaries,  may  attain  the  size  of  a  list  and  even  larger. 
[  The  contents  of  cysts  depend  ui^ou  the  nature  of  the  tissue  in  which 
1  they  aie  formed.  Thus  the  cysts  of  the  sebaceous  glands  and  hair-folli- 
'  cles  (atlirroma)  contain  a  ijultaceous,  white,  or  grayish-Avhite,  more  rarely 
!  brown,  mass,  which  consists  essentially  of  squamous  cells,  in  iiart  show- 
'  ing  cornitication,  and  also  of  fat-globules  and  cholesterin.  The  cysts  oc- 
icurring  in  mucous  glands  contain  a  mucous  fluid  which  is  either  clear, 

or  white  and  cloudy,  as  the  result  of  the  j)reseuce  of  cellular  elements. 


Fig.  128.-Pancreaa  cyst,  due  to  dilatation  of  branches  of  Wirsnncr's  duct.    a.  Gland-tlssue  ;  /j,  cysts ;   c , 
I  transverse  section  of  artery ;  (f,  longitudinal  section  of  vein.    Natural  size. 


' HjEmorrhage  into  a  cyst  from  the  cyst-wall  gives  a  red  or  brow  ii  color  to 
jthe  contents.  When  great  numbers  of  cells  are  present  in  the  cyst-con- 
^tents,  this  may  become  couverted  into  a  semi-solid  fatty  mass,  which 


260  THE    RETROGRADE    CHANGES. 

may  undergo  calcification.  Cysts  of  the  thyroid  and  kidneys  contain 
colloid  masses,  or  a  clear  though  occasionally  cloudy  fluid. 

Retention=cysts  lined  with  endothelium  may  develop  from  blood 
and  lynipli-\  essels,  lymph-spaces,  bursic,  and  tendon-sheaths.  Here  also 
the  content  of  the  cyst  is  dependent  upon  its  place  and  mode  of  origin. 

As  retention-cysts  increase  in  size  the  stretching  of  the  cyst-wall 
would  idtimately  lead  to  a  defect  in  the  continuity  of  the  wall  if  no  new 
fonnaiion  of  tissue  took  place.  Cyst  formation  is,  therefore,  not  purely 
a  dege^erati^"e  i^rocess;  such  a  new  formation  of  tissue  takes  place  firtst 
in  the  epithelial  or  endothelial  lining  of  the  cyst,  but  the  connective- 
tissue  elements  of  the  wall  also  increase,  so  that  in  spite  of  the  stretching 


Fk;.  129.— Hydrops  of  the  Fallopian  tube,  with  perisalpingitic  and  periovarian  adhesions,  rt,  Uterus; 
?*,  utftiiie  portion  of  the  tube;  l\  abdominal  end  of  tube,  showing  cystic  dilatation  and  adhesions  with  the 
neighboring  parts;  </,  ovarium  ;  c,  membranous  adhesion.     Two-thirds  natural  size. 

the  wall  of  the  cyst  becomes  no  thinner,  and  under  certain  condition; 
may  even  increase  in  thickness.  Moreover,  cyst  formation  is  ofter: 
associated  with  a   pathological  formation  of  new  glandular  tissue, 

and  in  this  way  constitutes  a  secondary  change  in  hypertrophic  or  tumor; 
like  growths.  It  is,  therefore,  sometimes  impossible  to  draw  a  sharjilim 
between  the  simiDle  cystic  dilatations  of  preexisting  gland-canals  anc 
gland-spaces,  and  those  tumors,  the  cystomata,  which  are  characterize* 
by  cyst  formation  (see  Cystoma).  Endothelial  cysts  may  also  develop  o% 
of  neivly  formed  lymph-spaces  and  lymph-vessels. 

A  second  form  of  cyst  is  the  degeneration=cyst,  which  arises  throng 
the  partial  disintegration  and  liquefaction  of  a  tissne.  Cysts  formed  i; 
this  manner  occur  in  the  brain,  hypertrophic  thyroids,  and  in  tumon 
They  may  contain  a  clear  or  cloudy,  or  at  times  haemorrhagic  exudate. 

A  thiid  form  of  cysts  i-esults  from  the  formation  of  a  connective 
tissue  capsule  aiound  foreign  bodies,  which  have  found  entrance  to  tls 
tissnes,  as,  for  e.\am]»le,  about  a  bullet;  or  also  about  necrotic  areas,  ( 
hsemorrhagic  extravasates. 

A  fourth  \ariety  of  cysts  is  formed  by  parasites  which  pass  thro 


i 


C  Y.ST-F< )  K  MAI'  I  < )  \ .  'if  i  1 

a  cystic  stage  iu  the  course  of  their  (h'Vt'ln])iiu'iit   in  tJie  body,  and  aic 
likewise  suiTOunded  by  a  co)i)icc1irr-tissiif  capsitlr. 

Literature. 

(Brtc)iti(>)i-('i/.sfs.') 

Aschoff:  Cysten.     Ergebuisso  d.  nUg.  Palh.,  11.  Jaliig.,  Wieshadon,  181)7  (Lit.). 
Bard  it  Lemoine:   De  la  maladie  kystique  essentiflle  des  oigaues  gland u la irt-s,  Paris, 

ISilO, 
Chiari:  Gcuise  der  sog.  Atheromcysten.     Zeitschr.  f.  Hcilk.,  xii.,  1891. 
Franke:  Blutcyste  der  seitlicheu  HalsacijciKl.     Dvut.  Zcitsclir.  L  C'liir.,  'Js  Bd.,  1S88 

(Lit.). 
Hennes:  Augeb.  Auswlichse  am  Halse.     Arch.  f.  Kiiuk-rlieilk.,  i.\.,  1888  (Lit.). 
Hess:   Leber  eiue  subcutane  Fiiminercystc.     Beitr.  v   Ziegler,  viii.,  1890. 
Kiihne:  Pathol.  Histologie  der  Cystenliilduug.     Virch.  Arch.,  158  Bd.,  1899. 
Marchand:  Cysteu.     Eulenburg's  Realencyklop.,  1894  (Lit.). 
Nordmann:  Galaktocele.     Virch.  Arch.,  147  Bd.,  1897. 
Philippson:    Auatomische    Untersuchungeu  liber   Nierencvsteu.     Virch.   Arch.,    Ill 

i'.d..  isss. 
V.  Recklinghausen:  Ueber  die  Raniila,  die  Cyste  der  Bartholin'schen  Druse  uiid  die 

FlininuTcx  stc  der  Leber.     Virch.  Arch.,  84  Bd.,  1881. 
Richard:  Gcsclnvlilste  der  Kiemenspalteu.     Beitr.  v.  Brims,  iii.,  1888. 
Sabourin:  La  dt'iicnerescence  kystique  du  foie  et  des  reins.     Arch,  de  phys.,  x.,  1882. 
Sasse:  Cysten  der  .■\Iamma.     Arch.  f.  klin.  Med.,  54  Bd.,  1897. 

Terburgh:  ICbcr  Leber-  und  Niereucysten.     Inaug.-Diss.  v.  Freiburg,  Leiden,  1891. 
Torok:  Kutsttliuiii:  der  Atheromcysten.     Monatssclir.  f.  prakt.  Derm.,  xii. 
Virchow:  Die  kraukhaften  GeschAvulste,  i.,  Berlin,  1863. 


CHAPTER  VI. 


Hypertrophy  and   Regeneration.     Results  of  Tissue^ 
Transplantation.     Metaplasia. 

I.  General  Considerations  Concerning  the  Processes  Known  as 
Hypertrophy  and  Regeneration,  and  the  Accompanying  Cellular 
Changes. 

§  76.  In  a  general  sense,  hypertrophy  is  an  increase  in  the  size  of  a 
tissue  or  organ,  due  either  to  an  increase  in  the  size  or  in  the  number  of  the  in- 
dividual elements,  in  snch  a  way  that  the  structnre  of  the  hypertrophic 
tissue  is  like  that  of  the  nor- 
mal, or  at  least  does  not  differ 
essentially  from  it. 

In  a  more  limited  sense  hy- 
pertrophy  is  an  increase  in  size 
due  to  an  enlargement  of  the  in- 
dividual elements  alone;  the  en- 
largement due  to  an  increase  in 
the  number  of  the  individual  ele- 
ments being  designated  as  hy- 
perplasia. 

Hypertrophy  may  result 
from  morbid  impulses  inherent 
in  the  germinal  cells,  or  from 
influences  acting  during  the 
life  of  the  individual. 

If  an  abnormal  tissue-in- 
crease occurs  during  the  period 
of  embryonal  development,  or 
of  extra-uterine  growth,  and  if 
no  influences  are  recognizable 
that  would  account  for  the  in- 
creased growth,  the  condition 
may  be  explained  as  the  result 
(tf  a  congenital  predisposition, 
and  may  be  designated  as  a 
hypertrophy  due  to  a  con= 
genital  anlage.  If  the  en- 
largement affects  the  entire  body,  for  example,  if  a  newly  born  chil-; 
weighs  5-8  kgm.,  or  if  an  individual  should  reach  the  height  of  180-20; 
cm.,  tlie  condition  is  called  a  general  giant  growth.  When  the  ei 
UirgenuMit  affects  only  individual  parts  of  the  body,  as,  for  example,  tb 
entire  head  or  one-half  of  it,  or  one  extremity,  or  a  finger,  or  the  vuh'f' 
it  is  called  a  partial  giant  growth.  The  giant  growth  of  several  pan 
of  one  side  of  the  body  is  designated  a  half  giant  growth  ;  one  involvir 

2G3 


Fig.  1'^'\ —Elephantiasis  femonim  neuromatosa 


HYPERTROPHY    AND     1 1  Y  I>KI{1'LASIA. 


208 


all  the  body-parts  is  very  rare.     Hypeitrophic  orowths  of  the  skin  and 
subcntaueous  tissues,  leading  to  a,  disfioinvinent  suggesting  the  ai)i)ear- 

anee  of  the  skin  of  the  ]faehyd«'rniata, 
are  known  as  elephantiasis  (Figs,   l.to, 

In  hypertrophic  growth  of  an  ex- 
tremity or  of  Ji  tinger  all  the  elements 
of  the  same  are  uniformly  enlarged. 
In  elephantiasis  of  the  extremities  the 
connective  tissue  of  the  skin  and  sul)- 
cutanecms  structures  is  especially  likely 
to  become  increased;  but  the  develop- 
ment and  structure  of  these  gi'owths 
vary  greatly.  In  one  case  all  tlu^  <'on- 
uective-t issue  elements  may  be  uniform- 
ly increased,  iu  another  case  oidy  indi- 
vidual elements;  as,  for  example,  the 
connective  tissue  of  the  nerves,  blood- 
or  lymph-vessels ;  or  at  least,  the  path- 
ological new-formation  takes  its  start 
from  these.  It  is  therefore  possible  to 
distinguish  different  forms  of  elephan- 
tiasis according  to  the  structure  of  the 
hyi>ei-trophic  part:  eleplanitiasis  neuro- 
matosa (Fig.  I'M)),  angiomatosa,  Jymphan- 
f/iectatica  (Fig.  131),  Jipomatosa,  fibrosa, 
etc. 

If,  as  a  result  of  some  peculiar  pre- 
disposition of  the  skin,  there  occurs  a 
hypertrophy  of  the  horny  layer  of  the 
epidermis  (Fig.  i;>2,  c),  so  that  the  skin 

becomes  covered  with  horny   plates,   scales,   or  even  with   spines,   the 

condition  is  designated  ichthyosis. 


Fii,.  lil.— Lkpli.uitiaM^  truiib  Ijmphau 
piectatiea. 


'"4 


Fig.  l.J^  — l(htli\f)sis  (onfrcnita.  Sertion  throufrh  the  skin  of  the  truni  of  the  body  (alro^ol,  plcrocar- 
mine.)  a.  <  oriuin,  with  frlainK,  /*,  papillarv  ho(h,\\ith  rHe  MalpiKhii ;  r,  h\pei trophic  horny  layer  of 
lue  epidermic ,  (/,  dilated  hair-follicles,  lined  with  horny  epithelium  ;  c,  hair?      x  4<», 


264 


THE    PROGRESSIVE    CHAXGES. 


This  change  may  be  present  even  at  birth  (ichthyosis  congenita)  ;  and 
the  new-born  child  (Fig.  133)  may  be  wholly  covered  with  hard  horny 
plates,  which  ha\  e  been  split  open  at  different  points  as  the  resnlt  of  the 
growtli  of  the  underlying  tissues. 
The  pathological  cornification  af- 
fects chietly  the  surface  (Fig.  132, 
c),  but  may  extend  also  into  the 
hair-follicles  (Fig.  132,  d). 

In  other  cases,  at  a  later  period 
of  development,  as  during  the  first 
years  of  life,  localized  thickenings 
of  the  horny  layer  may  develop, 
consisting  of  either  small  scales  or 
plates,  or  larger  ones,  giving  the 
skin  a  rough  and  checkered  ap- 
pearance. The  corium  and  the 
papillte  are  usually  not  involved  in 
the  ichthyosis ;  but  occasionally  the 
papillary  bodies  may  be  hypertro- 
phic and  enlarged,  thus  increasing 
the  rough  and  nodular  appearance 
of  the  surface  {ichthyosis  hi/.sfri.r). 
When  the  excessive  cornification 
is  sharj^ly  limited  to  areas  of  small 
size,  there  are  formed  circum- 
scribed warts  with  rough,  epithelial 
covering,  which  are  known  as  ich- 
thyotic  warts.  In  rare  cases  there 
may  be  developed  a  more  exten- 
sive horn^"  layer  over  the  hyper- 
trophic papillae,  whose  scales  are 
arranged  at  right  angles  to  the 
surface  of  the  skin ;  and  these  oc- 
casionally may  attain  to  such  size 
that  they  are  called  cutaneous 
horns  (Figs.  134,    135). 

The  hypertrophic  development  of  hair  over  those  parts  of  the  body 
where  only  downy  hair,  or  even  no  hair  at  all,  should  be  found  is  known 
as  hypertrichosis.     Such  an  abnormal  hairiness  may  cover  a  larger  or 

smaller  area  of  the  body, 
and  depends  either  upou' 
a  persistence  and  abnor-' 
mal   development  of  thej 
lanugo    (hypertrichosis 
lanuginosa  foetalis)  (Fig.j 
13()),   or  upon  a  patholo- 
gical de^•elopment  of  the 
secondary  hairs.     An  ex- 
cessive growth  of  the  nailsj 
leads    to     the    condition; 
known    as     hyperonychia, 
followed  by  a  claw-like  deformity  of  the  same   desig. 
It  is  to  be  noted,  however,  that   the  patholog 


Fig.  1J4  — Corau  cutanenm, 
from  back  of  hand.  (Natural 
size.) 


Fig.  13.5.— Corau  cutaneum, 
fnjin  arm.     (Natural  size.) 


which    is    often 

iiated   onychof/ryphosis 

ical  over-growths  of  the  nails  aie  usually  acquired, 


TISSrE-IlYPIOHTKOPIIIKS    OF    CONGENITAL    OHKJIN. 


2G5 


Kext  to  the  enliirg-eiuonts  associated  Avith  geneial  or  ])ailial  ^iaiilism 
the  bones  most  frequently  undeij;o  a  form  of  hyperlroi)hY  eoirespoiidiiin- 
to  the  congenital  eU'phantiasis  of  the  skin.  Tlie  head  is  usually  affected, 
the  bones  of  Avhich  may  uiidere,o  a  veiy  marked  enlargement  (l^'ig.  1.'>T), 
leading  to  a.  deformity  in  which  the  i>atient\s  head  comes  to  resemble  that 
of  a  lion,  hence  the  name  leontiasis  ossea.  Fuither,  theie  ol'ten  develoj) 
upon  the  skull  or  other  bones  of  the  ])ody  circumscribed  bony  giowt lis 
known  as  exostoses,  Avhich  are  inherited  and  not  depentUMit  ui)on  extiin- 
sic  inlluences. 

In  the  internal  organs  hypertrophic  processes  dependent  purely  upon 
iutriusic  causes  are  rare;  but  the  brain,  for  example,  may  reach  an 
abnormal  size. 

It  cannot  always  be  definitely  stated  to  what  extent  hypertrophy  of 
the  tissues  is  to  be  attributed  to  a 
congenital  predisposition,  inas- 
much as  many  exti'insic  intluences 
are  able  to  produce  proliferations, 
of  tissue  similar  to  those  due  to 

I 


Fig.  13C.— Heart  of  a  hairy  individual,  a  Wduian. 
(After  Hebra.) 


Fig.  ]37.— Lt'ontiasis  ossea.  occurrinp  in  a  boy  af- 
fected with  general  giant-growth.  U)bser\'ed  by 
liiihl.) 


intrinsic  causes.  For  example,  cutaneous  horns  and  elc]>hantiasis-like 
thickenings  of  the  skin  may  develop  as  the  result  of  inllanimat  ion. 
i  In  general,  the  early  ai:>pearance  of  a  hypertro]»hic,  growth,  the 
!  hereditary  nature  of  the  pathological  peculiarity,  and  tlu^  absence  of  any 
j  external  etiological  factoi',  speak  for  the  congenital  natiiieof  the  condi- 
j  tion.  The  fact  that  later  influences  may  apparently  cause  the  gi'owth 
1  does  not  i)reclude  the  existence  of  a  congenital  predisposition.  Thus  the 
I  excessive  bony  growths  of  the  head  above  mentioned  may  follow  trauma 
j  or  acute  inflammations.  External  influences  may  therefoi-e  be  the  excit- 
I  ing  cause  of  the  proliferation,  but  not  tlu^  pi-iinary  cause  of  the  same; 
j  since  M-e  know  by  experience  that  the  gi\<Mi  injuiious  intlnenccs  ai'<'  able 
.  to  produce  such  changes  only  in  tissues  possessing  a  s])ccial  ]»rcdisposi- 
tion. 

N'ot  infrequently  an  abnormal  tendency  to  excessive  growth  may  sho\v 


266  THE    PROGRESSIVE    CHANGES. 

itself  iu  a  premature  development  of  certain  organs,  the  structure  remaining 
normal.  The  exterual  aud  iuternal  sexual  organs  are  most  frequently 
affected.  Girls,  even  in  the  first  years  of  life,  may  show  a  development 
of  breasts  and  external  genitals  and  a  growth  of  hair  corresponding  to 
that  of  the  sexually  ripe  woman ;  aud  menstruation  may  be  established 
at  this  early  period. 

The  size  of  tlie  entire  body  as  -well  as  of  its  separate  parts  and  organs  sliows  con- 
siderable variation  within  physiological  limits,  accoi-ding  to  the  race,  family,  and  indi- 
vidual. The  variation  in  the  relation  of  the  size  of  single  parts  aud  organs  to  that  of 
the  entire  body  is  less  marked. 

The  average  height  of  the  body  in  well-built  individuals  is,  according  to  Vierordt 
("Daten  n.  Tabellen  fiir  Med.,"  Jena,  1893),  as  follows:  INlen  173  cm.,  women  160  cm. ; 
of  the  new-born,  males  AIA  cm.,  females  46.75  cm.  The  average  body-weight  in 
Europe  is  for  men  about  6.j  kgm.,  that  of  women  about  55  kgm.,  that  of  the  new-born 
about  3,250  gm. 

The  averasre  weight  of  the  internal  organs  is  as  follows,  the  figures  in  parentheses 
being  for  the  new-bora:  Brain  1,397  (385)  gm.,  heart  304  (24)  gm.,  lungs  1,172  (58) gm., 
liver  1,612  (118)  gm.,  spleen  201  (11.1)  gm.,  right  kidney  131,  left  kidney  150  gm.,  both 
kidneys  299  (23.6)  gm.,  testicles  48  (0.8)  gm.,  muscles  29,880  (625)  gm.,  skeleton  11,500 
(445)  gm.  E.xpressed  in  percentages  of  tlie  body-weight  the  figures  for  adults  and  new- 
born are  (the  latter  in  parentheses):  Heart  0.52(0.89),  kidneys  0.48  (0.88),  lungs  2.01 
(3.16),  stomach  and  intestines  2.34  (2.53),  spleen  0.346  (0.41),  liver  2.77  (4.30),  brain  2.37 
(14.34),  adrenals  0.014  (0.31),  thymus  0.0086  (0.54),  skeleton  15.35  (16.17),  muscles  43.09 
(23.4).  ^ 

Literature. 

{Tissue- Ilypertroxjhy  of  Congenital  Origin.) 

Arnheim:  Cougen.  halbseitige  Hvpeitrojihie.     Vircli.  Arch.,  154  Bd.,  1898  (Lit.). 

Baas:  Das  Hornhauthorn.     Cbl.  f.  allg.  Patli.,  viii.,  1897. 

Bartels:  Abnorme  Behaarung.     Zeit.  f.  EthnoL,  viii.,  1896;  Affeumenschen,  ib.,  xvi., 

18S4. 
Behrend:  Hypertrichosis.     Eulenburg's  Realencyklop.,  1896  (Lit.). 
Brandt:  Hundemenschen.     Biol.  Cbl.,  xvii.,  189^ 

Bruns:  Ueber  Rankenneurom.     Virch.  Arch.,  50  Bd. ;  Beitr.  z.  klin.  Cliir.,  1891. 
Busch:  Riesenwuchs  der  Extremitateu.     Arch.  f.  klin.  Chir.,  vii.,  1866. 
Carbone:  Ictiosi  congenita.     Arch,  per  le  Sc.  Med.,  xv.,  1892. 
Caspary:  Ichthyosis  congenita.     Vierteljahrsschr.  f.  Derm.,  xiii.,  1886. 
Chiari:  Ueber  Hypertrichosis.     Prag.  med.  Woch.,  1890. 
Demme:  Halbs.  Muskelhypertrophie.     37.  Jahresber.   d.  Jenner'schen  Kiuderspitals, 

Bern,  1890. 
Ecker:  Ueber  abnorme  Behaarung  des  Menschen,  Braunschweig,  1878. 
Esmarch  u.  Kulenkampff:  Die  elepluintiastischeu  Formen,  Hamburg,  1885. 
EsofF:  Iclithyosis.     Yircli.  Arcli.,  60  Bd.,  1877.  ' 

Ewald:  Hyix-rtrophie  der  Hand.     Virch.  Arch.,  56  Bd.,  1872.  ! 

Fischer:  Rii-scnwuchs  der  Exticmitntcn.     Dcut.  Zeitschr.  f.  Chir..  xii..  1880. 
Friedrich:   Ilalhscitige  congcnitale  Koiilliypcrtn.pliie.     Virch.  Arch.,  28  Bd.,  1863. 
Fuchs  :  Riesenwuchs  bei  Neugeb.  (6100  und  7550  gm.).     Mlinch.  med.  Woch.,  1908.    ' 
Hornstein  :  Halbscitiger  Riesenwuchs.     Virch.  Arcli.,  133  Bd.,  1893. 
Hiirthle  u.  Nauwerck  :  Fibroma  mollusc,  u.  congen.  Elephantiasis.     Beitr.  v.  Zieg- 

Icr,  i.,  issfi. 
Jacobson:  Universeller  Riesenwuchs.     Virch.  Arch.,  139  Bd. ,  1895. 
Jordan:  Pathol. -anat.  Beitr.  z.  Mcpliantiasis  congenita.     Beitr.  v.   Ziegler,  iii.,   1890. 
Kiwull:    Zur   Casuistik   der  lialbseitisien   Gesichtshj'pertrophie.     Fortschr.   d.   Med..i 

viii.,  1890. 
Klein:  Pubertas  praecox.     Dcut.   med.  Woch.,  1899.  ' 

Kussmaul :  Geschlechtliche  Friihreife.     Wiirzb.  med.   Zeitschr.,  1863. 
Lesser:  Hypertrichosis  anomalis.     Z.  f.  klin.  Med.,  41  Bd.,  1900. 
Mitwalsky:  Hauth()rner  der  Augenadnexa.     Arch.  f.  Derm.,  27  Bd.,1894. 
Nonne:  Elephantiasis  congenita  hereditaria.     Virch.  Arch.,  125  Bd..  1891. 
Poisson:  lIy]M'rostose  dill'use  des  maxillaires  superieures.     Sem.  med.,  1890. 
Poumayrac":  Et.  sur  riiypertrichosis,  Bordeaux,  1893. 
V.  Recklinghausen:  DiC  innltijden  Fibrome  der  Haut,  Berlin,  1882. 
R6na:   Iclithyosis  im  .liiiiglingsalter.     Arch.  f.  Derm.,  xxi.,  1889. 
Spietschka:"  Ueber  Elephantiasis  congenita.     Arch.  f.  Derm.,  xxiii..  1891. 


I 


ACQUIRED     llVl'KUTKOl'HY. 


2g: 


Trelat  (  t  Monod:  De  i'liypi'i-tidpluL'  uniliitorale.    ^\rcli.  gcii.  de  ined.,  1869. 
Unna:  Kcratonia  palmare  ct  plant,  congen.     Vicrtt'ljulirsschr.  f.  Derm.,  x..  1883. 
Virchow:   llaiull)uch  dcr  spec.  Putliol.,  i.,  1804:  Die  krankliaften  Geschwiilste,  1865. 
Wiedersheim :  J)er  Ban  des  3Ieiiseiieii,  Freihurii;,  18i»:i. 

>j  77.  The  hypertrophies  of  the  tissues  due  wholly  to  extrinsic 
influences  without  the  aid  of  a  congenital  predisposition  owe  llicir 
origin  either  to  au  increase  in  the  activity  of  the  tissne,  to  diniini.shcd 
use,  defective  retrograde  change,  or  finally  to  prolonged  or  fi'eiinently 
repeated  mechanical,  chemical,  and  infections  irritations  of  the  tissues. 
Under  certain  conditions  the  removal  of  pressure  may  also  give  rise  to  a 
localizi'd  hypertrophy. 

Hypertrophy  from  overwork  is  most  frequently  observed  in  the  case 
of  muscles  and  (jlands,  but  may  occur  also  in  other  tissues.  If  the  heart  is 
called  upon  to  do  an  extra  amount  of  work  as  the  result  of  diseased  con- 


FiG.  138,— Transverse  section  of  a  heart  stiowiiiir  liypertrophy  of  the  left  ventricle,  resulting  from  aortlc 
stenosis  and  insufMciency.    d,  Left,  /<,  the  rij-'ht  ventriele.     ra'diiccil  ,'„. 


ditions  of  the  valves,  aorta,  or  kidneys,  and  if  such  conditions  exi.st  for 
some  time,  that  part  of  the  heart-museh^  upon  which  the  exti-a  work  falls 
suffers  a  more  or  less  pronounced  hyi)ertrophy  (Tig.  1-38),  so  that  as  a 
result  the  mass  of  the  heart  may  reach  threefold  that  of  the  normal. 

In  a  similar  manner  the  striated  mnsdes,  and  the  unstriped  muscle  of  the 
bladder,  ureters,  uterus,  intestine,  and  ItJood-vesseJs  may  become  hypertrojjhic 
as  the  residt  of  persistent  increase  in  their  activity. 

As  the  result  of  an  increase  of  the  sup])oiting  strain  from  whatever 
cau.se  the  hones  may  become  thickened,  tind  the  bony  trabecuhe  of  the 
medullary  portion  become  increased  in  size. 

Of  the  glands,  the  Iddneys,  and  liver  in  particuhir  are  able  to  change 
their  size  according  to  the  functional  denmnd.s,  and  may  consequently 
pre.sent  a  marked  hypertrophy.  Should  one  kidney  be  destroyed  the 
remaining  one  may  become  so  eidarged  that  it  may  i-each  approximately 


2GS 


THE    PROGRESSIVE    CHANGES. 


Fig.  139.— Hypertrophy  of  an  incisor 
tooth  of  a  white  rat,  the  result  of  an 
oblique  position  of  the  jaw.     (Natural 


the  same  weight  that  the  two  kidneys  together  originally  possessed. 
Likewise  the  liver  after  a  destriictiou  of  a  part  of  its  parenchyma 
through  disease  may  make  good  its  loss  by  a  hypertrophy  of  the  remain- 
ing tissue.  Since  in  this  way  a  compensation  for  the  defect  and  a 
restoration  of  the  normal  function  is  brought 
about,  such  a  tissue-increase  may  be  ap- 
propriately designated  compensatory  hy- 
pertrophj'.  The  same  term  may  also  be 
applied  to  muscle-hypertrophy,  if  through 
it  functional  disturbances  are  compensated. 
A  similar  compensatory  hypertrophy  is  said 
to  occur  also  in  the  case  of  adrenal  tissue. 
In  the  case  of  other  glands,  such  as  the 
salivary  glands,  ovaries,  testicles,  and  mam- 
mary glands,  such  a  C(^mpensatory  hyper- 
trophy either  does  not  occur  at  all,  or  takes  place  only  during  the 
jDcriod  of  development.  The  loss  of  an  ovary  or  testis  in  adult  life  can 
hardly  result  in  an  increased  activity  or  hypertrophy  of  the  remaining 
organ.  Extirpation  of  the  larger  part  of  the  thyroid  gland  is  not  fol- 
lowed by  any  pronounced  hypertrophy  of  the 
remaining  portion ;  but,  on  the  other  hand,  the 
hypophysis  undei'goes  an  enlargement  m  hich 
must  be  regarded  as  compensatory.  In  the 
case  of  the  lungs,  an  increase  in  the  activity  of 
one  portion  after  the  loss  of  other  x)arts  re- 
sults usually  in  a  permanent  overdistention 
which  may  lead  eventually  to  atrojihy.  On 
the  other  hand,  if  during  embryonic  life  a  de- 
fective development  of  one  lung  takes  place, 
the  other  lung  may  undergo  a  comi)ensatory 
growth,  which  in  the  case  of  total  agenesia  of 
one  lung  may  reach  a  very  pronounced  degro(\ 
For  the  other  organs  the  general  jiriiHiplc 
maybe  applied  that  compensatory  hypertro- 
phy is  the  more  perfect  the  younger  the  indi- 
vidual. In  the  case  of  the  brain  a  compen- 
.satory  growth  of  one  part  after  the  loss  of 
another  is  possible  only  during  the  early  stages 
of  devel()i)ment. 

Hypertrophy  from  lessened  use  occurs  in 
the  case  of  tissues  which  aj-e  subjected  to  a> 
constant  use.  Thus,  for  example,  a  dimin- 
ished desquamation  of  the  horny  layer  of  the 
epidermis  leads  to  its  pathological  thickening. 
If,  as  the  result  of  the  destruction  of  an  op- 
posing tooth  or  an  oblique  position  of  the 
t€eth,  the  incisor  teeth  in  rodents  are  not 
worn  down  by  use,  they  may  grow  out  into 
long  and  carved  liisks  (Fig.  1.39).  Likewise 
Ihe  finger-  and  toe-nails  may  reach  an  ab- 
normal size  either  from  lack  of  wear  or  fnmi 
being  left  uncnt.      Hypertrophy  due  to  de= 

fective    retrograde   change  occnrs   in  organs   which    after   a   definite, 
period  of  physiological  growth  undergo  a  diminution  in  size.     For  ex- 


Fi(i.  I4n.-?;iriiiiatiasis  scroti  in  a 
Saiiiuan  niiieti't'ii )  ears  of  age.  tht- 
ter  Uthemann,  DcKfst/ic  mcd.  Wi>- 
vhcnschr.,  1895.) 


ACQilHKI)     HVPKirrHOl'llV 


2(39 


ample,  the  uterus  after  ])ivunaiu'y  may  rciiKiin  aSiioinmlly  lai'j;'e  as  llie 
result  of  a  failure  of  involution.  The  tli>  niusiilaiul,  wliich  should  be^in 
to  atiMiphy  aftei-  the  tenth  year  of  life,  may  persist  for  a  much  longer 
period  than  normally.     In  bones  whose  conligu rat  ion  lias  been  brought 

aitout  UM(U'r  the  inlhnMU'(i  of 
the  suri'onndings  by  means 
of  nil  allciualioii  of  bnild- 
iiig-ui*  ;ind  tcariiig-dowii,  a 
lessening  of  pressure  may 
be  t'oihtwcd  by  li_\  jxTt  i(»]ihy. 
In  idiots  uhose  brains  are 
/'  -.         ^*^'''''^'^^^  deficient  in  size  there  is  very 

often  seen  a  hyperostosis  of 
the  inner  surface  of  the  base 
of  the  skull  (Chiari).  A 
unilateral  hyperostosis  of 
the  skull  is  associated  with 
a    unilateral    hypoplasia    of 


Fig.  Ul.-^cioinejral.v 
artliri)putliv,  aeci 


iicc(ii-diii>r  t(i  Ei'l)and  Arnold.    (Osteo- 
ding  to  Marie  and  Souza-Leite.) 


the  brain. 

Frequently  repeated  or 
long=protracted  mechani= 
cal,  thermal,  chemical,  or 
infectious  irritations  give 
ris(i  to  proliferativ(^  proc- 
esses leading  to  tissue-hy- 
pertrophies, which  accord- 
ing to  their  etiology  and 
course  must  be  regaided  as 
clu-onic  inhainmations;  and 
luicli  new-formations  of  tissue 
may  therefore  be  regarded  as 
an  inflammatory  tissue=hy= 
pertrophy.  They  are  char- 
acterized very  often  by  the 
fact  that,  in  the  enlargement 
of  the  oi'gan,  not  all  of  its  parts  are  equally  involved  in  the  hypertroi)hy  ; 
but  certain  individual  elements,  usually  the  conuective  tissue,  occasion- 
ally also  the  epithelium,  undergo  hypertrophy  to  an  especial  degree,  so 
that  the  drudure  of  the  organ  (skin,  gland,  etc.)  is  no  lonf/cr  u-liol/i/ 
ilipical. 

If  the  skin  is  frequently  subjected  to  mechanical  irritation  and  i)ress- 
ure,  as,  for  example,  the  toes  through  an  iil-litting  boot,  there  may  arise 
in  coiise(|uence  thickenings  of  the  liorny  layer  of  the  epidermis,  known 
US,  cnllii.s  i)v  corn  (clavu-s).     Prolonged  irritation  of  the  skin  in  tiie  neigh- 
borhood of  the  genital  openings,  caused  by  gonorrho'al  discharges,  may 
cause  a  marked  elongation  and  l)ranching  of  the  pai)illie  with  an  accoin- 
paiiyiiig  thickening  of  the  epithelium,  leading  to  the  formation  of  the 
warty,  caulitlower-like  growths  knowu  as  vennral  mais  or  condi/lontoto 
I  acuminata.     Chronic  iutiammations  of  the  corinm  and  subcutaneous  tis- 
I  sue,  due  to  infection  or  to  animal  ])arasites  ( Fi/aria  JUincrofti),  not  infie- 
i  queutly  give  rise  to  extensive  librous  liyperti'oi)liies  of  the  tissue  known 
t  ^ elcphantkmfi  (Fig.  140).     Such  elephant iasic  hyix-rt  i()i)hies  of  the  1  issue 
j  may  attain  extraordinary  proixnt ions.     In  a  similar  maniK'r  there  may 
I  ocnur  in  the  bones,  as  the  result  of  chronic  infectious  ](rocess«'s  (syphilis, 


270 


THE    PROGRESSIVE    CHANGES. 


for  example),  extensive  hypertrophies  characterized  by  an  increased 
formation  of  bone-substance. 

In  the  majority  of  cases  of  those  tissue-hypertrophies  which  appear 
during  the  course  of  life  as  acquired  formations  caused  by  external  influ- 
ences, the  causa  efficiens  may  be  recognized  with  more  or  less  certainty; 
but  theie  are  also  many  cases  in  which,  at  the  present  time,  this  is  either 
wholly  impossible  or  possible  only  to  a  limited  extent.  For  example, 
there  occur  enlargements  of  the  spleen,  and  of  the  Jymphadenoid  tissue  of  thC; 
lymiDh-glands  and  of  the  lymph-nodes  in  the  mucous  membranes,  which 
are  of  the  nature  of  hypertrophies,  whose  causes  we  are  unable  to  recog- 
nize. Very  imperfect,  also,  is  our  knowledge  concerning  the  etiology  of 
the  enlargements  of  the  distal  portions  of  the  extremities  (Fig.  14:1),  resem-! 
bling  partial  giant-growth,  which  have  been  described  as  acromegaly 
(Marie),  pachyakria  (von  Eecklinghausen),  and  osteoarthropathie  hyper- 
trophiante  (Marie).  In  a  part  of  these  cases  there  are  an  associated  en 
largement  of  the  bones  of  the  face  and  deformities  of  the  spinal  columu.S- 
These  changes  api^ear  usually  in  youth  or  middle  age,  rarely  in  old  age, 
and  show  a  gradual  develoi^ment.  | 

So  far  as  anatomical  investigations  have  been  able  to  throw  light! 
upon  this  question,  the  pathological  change  consists  in  an  increase  of  all) 
the  tissues  of  the  terminal  i)ortions  of  the  extremities  and  of  the  face,  iu  I 
particular  of  the  bony  parts,  in  that  the  bones  become  thicker  (Fig.  142  j| 
and  at  the  same  time  become  the  seat  of  rounded  or  pointed  exostoses.;  ^ 
On  the  other  hand,  an  increase  in  the  length  of  the  bones  has  not  yei[ 
been  demonstrated  with  certainty  in  this  disease  (von  Eecklinghausen.;  > 


Fig.  1J2.— Skeleton  of  tho  hand,  with  \\y\M 


i-tropliie  hones,  from  the  case  of  acromegaly  pictured  i!i  FiR.  1 
(After  Arnohl.) 


Arnold).     The  disease  suggests  those  changes  which  are  seen  as  the  r< 
suit  of  certain  intoxications  or  infections,  for  example,  syphilis,  but 
is  not  possible  at  the  i)resent  time  to  assign  to  it  any  definite  cause. 

The  cause  and  nature  of  these  pathological  phenomena  are  as  yet  obscure;  andtl 
terms  mentioned  above  are  not  used  by  allauthors  with  the  same  meaning.  In  Ge 
many  the  designation  acromegaly  is  applied  to  all  forms  of  enlargement  of  the  ends 


ti 


ACQUIRED    IIYPEKTHOPIIV.  271 

the  extremities  which  lead  to  a  paw-shaped  deformity  of  the  hands  and  a  gigantesque 
appearance  of  the  feet,  while  Marie,  v>ho  first  described  these  conditions,  attempts  to 
draw  a  sharp  line  between  acromegaly  and  ostc''oartiiropatliie  hyperlrophiante.  He 
lioliis  that  in  acromegaly  the  hands  and  feet  aio  not  defornu'd.  l)Ut  are  synnnetricaily 
enlarged,  the  thickening  and  broadening  dinunisiiing  toward  tiie  tips  of  the  extremities, 
'so  that  the  terminal  phalanges  of  the  fingers  and  toes  are  l)ut  slightly  thickeneii,  while, 
on  the  other  hand,  in  osteoarthropathie  hypertrophiante  the  terminal  phalanges  are 
enlarged  so  as  to  resemble  drumsticks,  ;<nd  the  articular  ends  of  the  bones  are  irregularly 
thickened.  In  the  first  affection  the  lower  jaw  is  lengthened,  in  the  latter  it  is  thick- 
ened. Marie  believes  that  in  manj^  cases  osteoarthropathie  hypertrophiante  is  a 
sequela  of  inflammatory'  affections  of  the  lung-  and  pleurte,  and  designates  the  con- 
dition accordingly  as  osteoarthropathie  hypertrophiante  pneumique,  and  holds  that 
the  connection  between  these  processes  is  to  be  foimd  in  the  taking  up  into  the  body- 
:  fluids  of  poisonous  products  from  the  inflannnatory  foci  in  the  lungs,  so  that  the  affec- 
'  tion  of  the  bones  is  to  be  regarded  as  an  infectious  toxic  hypertrophic  infianunation. 
!  By  other  authors  the  causes  of  acromegaly  and  osteoarthropathie  hypertrophiante 
are  to  be  sought  in  a  congenital  predisposition  (^'il'chou■),  in  disturbances  of  the  sexual 
function  (Freiaul),  in  a  diseased  condition  of  the  hypophysis  {Ilenrol,  Klebs,  Tumhurini, 
von  Hunscmann,  Benda,  Stevens),  in  persistence  of  the  thymus  {Krh,  Klrhf^),  or  in 
'nervous  influences  (co?!-  Bechlinyhausen);  but  none  of. these  hypotheses  is  adetpiately 
'  supported  by  anatomical  and  clinical  observations.  The  frequent  association  of  acrome- 
galy v.ith  tinnors  of  the  hypophysis  of  different  kinds  has  been  definitely  determined, 
I  but  the  character  of  the  tumors  in  some  cases  would  indicate  an  increase  of  function, 
1  in  other  cases  a  diminution  or  loss  of  the  same.  Cagnettu  is  therefore  of  the  oj)inion  that 
a  primarj' disturbance  of  metabolism  underlies  the  condition  of  acromegaly,  so  that  both 
''  the  bones  and  the  hypophysis  are  stimulated  to  hyperplastic  proliferation.  Although 
the  investigations  made  up  to  the  present  time  do  not  permit  a  positive  conclusion  as 
;  to  the  nature  of  these  conditions,  they  show  that  they  do  not  represent  an  excessive 
,  growth  similar  in  nature  to  a  partial  giant  growth,  but  are  acquired  diseased  conditions, 
'  which  develop  either  as  independent  diseases  (acromegaly,  pachyakria),  or  as  sec- 
:  ondarj'  phenomena  in  the  course  of  other  diseases  (osteoarthropathie  hypertrophiante 
pneumique). 

The  cause  of  the  nodular  hj^pertrophy  of  the  thyroid  gland,  occurring  so  fre- 
j  quently  in  many  regions,  is  wholly  unknown. 

Literature. 

{Compensatory  Hypertrophii  of  Glands  and  of  the  Heart.) 

Beresowsky:  Compensatorische  Hypertrophic  d.  Schilddriise.     Beitr.  v.  Ziegler,  xii., 

1892. 
Bizzozero:  Accrescimento  e  rigenerazione  nell'  organismo.      Arch.  p.  le  8c.    Med., 

xviii.,   1894. 
Bostrom:  Beitr.  z.  path.  Anat.  d.  Niere,  Freiburg,  1884. 
Bozzi:  Untersuch.  iJber  die  Schilddriise.     Beitr.  v.  Ziegler,  xviii.,  189.5. 
Eckhardt:  Compensat.  Hypertrophie  der  Nieren.     Virch.  Arch.,  114  Bd.,   1888. 
Galeotti  u.  Villa-santa:  Komp.  Hypertrophie  d.  Niere.     B.  v.  Ziegler,  xxxi.,   1902. 
Grawitz  u.  Israel:  As  above,  ib.,  77  Bd.,  1879. 
Hodenpyl:  Apparent  Absence  of  the  Spleen  with  General  Compensatory  Lymphatic 

llyjifrplasia.     Med.  Rec,  1898. 
Horwath:  Die  Hypertrophie  des  Herzens,  Wien,  1897. 
Krahe:   ('om]j.  Hyp.  d.  Speicheldriisen.     Inaug.-Diss.,  Bonn.,  1888. 
Leichtenstern:  Comp.  Nierenhypertrophie.     Berl.  klin.  Woch.,  1881. 
Nothnagel:   I'eber  Anpassungen  u.  Ausgleichungen  bei    pathologi.schen  Zustiinden. 

Zfilschr.  f.  klin.  Med.,  x.,  1885;   xi..  1886;   xv.,  1888. 
Perl;  Coiup.  Nierenhypertrophie.     Virch.  Arch.,  .50  Bd.,  1872. 
Podwyssozky:  Exp.    Unters.    lib.    die    Regeneration    d.    Driisengewebe.     Beitr.    v. 

Ziegler,  i.,  1886. 
Ponfick:  Zur  Pathologie  der  Leber.     Virch.  Arch.,  118,  119,  and  138  Bd.,  1889-1894. 
V.  B-ecklingliausen:  Pathologie  des  Kreislaufes  u.  d.  Ernahrung,  Stuttgart,  1887. 
Ribbert:  Comp.  Nierenhypertrophie.     Virch.  .\rch.,  88  Bd.;    Compens.    Hypertr.   d. 

C.eschlechtsdru.sen.   Tb..  120  Bd.,  1890;  Compens.  Hypertrophie  u.  Regen.    Arch,  f . 

Entwickelungsmechan.,  i.,   1894. 
Rogowitsch:  Verand.    d.    Hypophyse   nach     Entfernung   d.    Schilddrii.se.     Beitr.    v. 

Ziegler,  iv.,  1889. 


272  THE    PROGRESSIVE    CHANGES. 

Sacerdotti:  Ipertrotia  compens.  del  reni.     Arch,  per  le  Sc.  IMecL,  xx.;    Virch.   Arch.f 

14(5  B(!.,  189G. 
Schuchardt:  Compensat.  Hypertrophie  d.  rechten  Lunge.     Virch.  Arch.,   101    Bd., 

LSS,5. 
Simmonis:  Compensat.  Hypertrophie  d.  Nebennieren.     Virch.  Arch.,  l.'iS  Bd.,  1898. 
Stieda:  \'erhalten  d.  Hypophyse  nach  Entfernnng  d.  Schilddriise.     Beitr.  v.  Ziegltr 

vii.,   1890. 
Stilling:  Compensat.  Hypertrophie  der  Nebennieren.     Virch.  Arch.,  118   Bd.,  1899. 
Tang-l:  Ueb.  d.  Hypertrophie  u.  d.  phys.  Wachsthum  des  Herzens.     \'irch.  Arch.,  116  ' 

Bd.,  isr.3. 

Velisch:  Compens.  Hypertrophie  d.  Nebennieren.     Virch.  Arch.,  154  Bd.,   1898. 
Wollmann:  Ein  Fall  von  Agenesie  der  Limge.     Inaug.-Diss.,  Freiburg,  1891. 
Ziegler:  I'rsachen  d.  pathol.  Gewebsneubildungen.     Intern.  Beitr.,  Festschr.  f.   Vir- 

cliow,  ii.,  1891. 
Zielonko:  (Stud.  iib.  die  Hypertrophie  des  Herzens.     Virch.  Arch.,  62  Bd.,  1865. 


{Acromeg'dii,   Pachnalcrla,    Ostvoioihropnthic    IFupoirophidnte,    and    Hyper- 
trophi/  of  the  ^7,»//.) 

Arnold:  Akromegahe,  Pachj-akrie  oder  Ostitis.     Beitr.  v.  Ziegler,  x.,  1891;   Beitr.  zur 

Akromegaliefrage.     Virch.  Arch.,  135  Bd.,  1893. 
Bamberger:  Knochenverand.  bei  chron.  Lungen-  u.  Herzkrankh.      Zeit.  f.  kl.  Med., 

xviii.,   1890. 
Benda:  Akromegalie.     D.  med.  Woch.,  1901. 

Brooks:  Acromegaly.     Archives  of  Neurology,  New  Tork,  i.,  1898. 
Cagnetto:  Bez.   z\v.  Akromegalie   u.   Hypophvsistumoren.     Virch.  Arch.,    176    Bd., 

1904. 
Chiari:  Basale  Schiklelhyperostose  bei  Idioten.     Verh.  d.  path.  Ges.,  ii.,  BerUn,  1900. 
Erb:   Uel)er  Akromegalie.     Deut.  Arch.  f.  kl.  Med.,  42  Bd.,  1888. 
Freund:  Ueber  Akromegalie.     Samml.  klin.  Vortr.,  Nos.  329-30,  Leipzig,  1889. 
Friedreich:  Hyperostose  des  gesammten  Skeletes.     Virch.  Arch.,  43  Bd.,  1863. 
Fritsche  u.  Klebs:    Ein  Beitrag  zur  Pathologie  des  Riesenwuchses,  Leipzig,  1884. 
Holsti:  Akromegalie  avec  autopsie.     Festkrift  fr.  Pathol.  Anatom.  Institutet  Helsing- 

fors,  1890. 
Israel:  Der  Akromegale  Knauerauf.     Virch.  Arch.,  164  Bd.,  1901. 
Lefebvre:  Des  deformat.  osteoarticulaires  consec.  a  des  mal.  de   I'app.   pleuropulmo- 

naire,  Paris,   1891. 
Marie:  Sur  deux  cas  d 'akromegalie,  hypertrophie  singuliere  non  congenitale  des  ex- 

tremites  et  cephalique.     Rev.  de  med.,  vi.,  1886;   De  I'osteoarthropathie  hypertro- 

phiante  pneumique.     lb.,  x.,  1890. 
Marie  ct  Marinesco:  Sur  I'anatomie  pathol.  de  I'akromegalie.     Arch,  de  med.  exp.. 

iii.,   1891. 
Minkowski:  Ueber  einen  Fall  von  Akromegalie.     Berl.  klin.  Woch.,  1887. 
Oestreich:  Ricsenwuchs  und  Zirbeldriisengeschwulst.     Virch.  Arch.,  157  Bd.,1899. 
Rauzier:  Osteoarthropathie  hypertrophiante  d'origine  pneumique.     Rev.   de    med. 

xi.,    1891. 
V.  Recklinghausen:  Ueber  Akromegalie.     Virch.  Arch.,  119  Bd.,  1890. 
Schmidt:  Akromegalie.    Ergebn.  d.  allg.  Path.,  v.,  1900  (Lit.). 
Schutte:  Path.  Anat.  u.  Aetiol.  d.  Akromegalie.     Vh\.  f.  allg.  Path.,  ix.,  1898   (Lit.) 
Souza-Leite:  De  I'akromegalie,  Paris,  1890. 
Spillmann  ct  Haushalter:  Osteoarthropathie    hvpertrophiante.     Rev.  de  med.,   x 

1X90. 
Sternberg:  Die  Akromegalie,  Wien,  1897. 

Stevens:  Case  of  Acute  Acromegaly.     Brit.  Med.  Journ.,  1903. 
V.  Strumpell:    Zur    Pathologie   d.   Akromegalie.      Deut.   Zeit.   f.  Nervenheilk.,   xi 

1.S97. 
Thomson:  Acromegaly  with  the  Description  of  a  Skeleton.     Journ.  of  Anat.,  xxiv 

1S91. 
Verstraeten:  L 'akromegalie.     Rev.  de  med.,  ix.,  1889. 
Virchow:  Uclier  Akromegalie.     Berl.  klin.  Woch.  and  Deut.  med.  Woch.,  1889. 


Regeneration  is  that  j>rocr.s'.s'  throv(/h  irhich  ti.%sues  which  have  hee 
destroyed  arc  restored.     Under  especial  conditions  this  restoration  ma 


§78. 


RKGEXERATION    AXI)    KIOPAIH. 


•273 


be  broujiht  about  by  an  enlargoniout  of  oxistiiifj  parts  of  cells  (i-c^onera- 
tion  of  axis-cylinders),  bnt  it  is  K.sudllj/ihr  rcmilt  of  urwJ'ornuiVion  of  cells, 
irhicJi   'rise  in  all  eases  t/iroi((/h  t/ie  dirisioH  (f  preexist  in//  cells. 

Kojioneration  prosnpposes  that  the  injured  tissue  is  capable  of  pro- 
liferation, and  is,  moreover,  a  phenomenon  which  is  in  all  cases  de])end- 
ent  npon  extrin.^ic  causes.  In  the  fnlly  developed  or^^anism  in  which 
the  ditfeient  tissues  and  orpins  haxe  icached  Iheir  ultimate  differentia- 
tion, e<ic/i  tissue  can  jnodace  oiili/  iieir  tissue  of'  its  oirii  or  a  closeli/  related 
kimi.  The  specificity  of  the  tissues  is  of  so  decided  a  natnre  that  epi- 
thelial cells  can  never  _uive  rise  to  connective  tissne,  noi- can  the  latter 
ever  ])roduce  epithelium.  Ectodermal  cells  cannot  i)rodnce  intestinal 
epithelium ;  kidney  ei)ithelium  can  i)i-oduce  only  cells  havinj;'  the  charac- 
ter of  kidney  epithelium,  but  never  liver-cells  or  those  of  mucous  glands, 
or  connective  tissue.  Muscle-tissue  can  arise  only  from  muscle-cells. 
Nerves  and  neuroglia  can  never  arise  from  connective  tissue.  Only  cells 
which  ai-e  V(»ry  closely  related  to  each  other  can  arise  from  the  same 
paicnt-t issue  or  pass  into  each  other.  Thus  the  connect i\e  tissue  of  the 
perit)steum  can  produce  either  ordinary  connect i\'e  tissne,  caitila,ii'e,  or 
bone — that  is,  tissues  which  are  closely  related  to  each  other,  and  which 


S?S?-; 


\.x 


I  Fig.  14a— The  skin-portion  of  a  laparotomy  wound  sixtnri  diiys  old  (Miill.-r's  lliiid.  Van  Gieson's). 
fn,  Kpitheliuni,  h,  coriiiin  ;  c,  subcutaneous  adipose  tissue ;  (/,  si;ir  in  coiiuin;  ( ,  new  cpiilieliuni;  /,  scar 
tin  adiiKise  tissue,    x  ;!8. 

•may  be  regarded  as  different  modifications  of  the  connect i\-e  tissne 
'substance. 

In  tissue  defects  in  iriiieh  onli/  siiu/le  cells  arc  lost  (as,  for  example,  in  the 
*loss  of  single  connective-tissue  cells),  or  in  the  case  of  a  nuM-*^  extensive 
idestruction  of  cells  without  an  interruption  in  the  continuitij  of  the  connective 
IS 


274  THE    PROGRESSIVE    CHANGES.  'i 

tissue  of  the  blood-vessels  (as  the  loss  of  localized  areas  of  the  surface  epi- 
theliam,  or  a  group  of  gland  cells  or  of  pulmonary  epithelium),  a  com- 
plete regeneration,  a  restitutio  ad  integrum,  may  take  place,  and  the 
tissue  l)e  restored  to  a  condition  corresponding  in  all  respects  to  that 
existing  before  tlie  injury.     After  all  injuries  in  whieh  the  eontinuity  of  the 


Fig.  IW.— Healing  ulcer  of  the  small  intestine,  with  formation  of  new  glaud-tulies  in  the  proliferatiui 
siibmiKiisa  rMiillcr's  tiiiid,  haMuatoxylin).  a.  Mucosa;  i»,  submucosa ;  c,  d,  muscularis;  f,  serosa ;/,  rt 
mains  (jf  tlic  iIikh-  o[  tlif  ulcer  not  yet  covered  over  with  epithelium ;  y,  overhanging  edge  of  the  ulcer;  h 
pnrtinii  Iff  iliKir  cif  ulcer  covered  with  epithelium;  i,  newly  formed  glands  in  the  submucosa;  fe,  deep  cryp 
lined  with  epithelium.     X  is. 

I 

mesodermal  supporting  tissue  is  hrol-en,  either  with  or  without  an  associate(j 
injury  to  tissues  of  ento-  and  ectodermal  origin,   the  regeneration  ii 
incomplete ;  iu  that,  at  the  point  of  injury  there  is  formed  a  tissu; 
Avhich  departs  more  or  less  from  the  normal  structure  of  the  affectC'i 
part,  and  shows  a  more  or  less  marked  loss  of  functional  capacity  aj 
compared  to  the  normal  tissue.     In  general  this  tissue  is  a  new  formatio! 
of  conneetive  tissue,  designated  as  a  scar  (Fig.  143,  d)  or  cicatricial  tissmj 
in  individual  organs  (as  in  the  heart-muscle)  also  called  a  eaUositj/,  tbl 
new  connective  tissue  resembling  other  formations  of  connective  tissu«| 
but  not  wholly  identical  with  them.     In  the  course  of  time  it  comet 
through  a  gradual  change  more  and  more  to  resemble  normal  tissii' 
Defects  of  the  skeleton  are  rei)laced  by  scar-tissue  which  arises  from  tl 
])eri().stenm  and  eiidosteum,  and  by  virtue  of  the  peculiar  properties  < 
tliese  tissues  there  develops  a  new-formation  of  houc-t issue  within  su( 
scars,  the  slructui-e  coming  to  resemble  closely  that  of  normal  bone. 

In  many  cases  the  cieatrieial  tissue  consists  purely  of  vaseularized  eo 
nedive  tissue  (Fig.  143,  d),  which  later  becomes  enriched  only  throuj 
the  in-growth  of  nerve- fibres  and  the  gradual  development  of  elastiefibn 
Scars  bordering  upon  ectodermal  or  entodermal  tissue  may  become  eo 
ered  by  a  neAv-foj-mation  of  epithelium  (Fig.  143,  e).  Occasionally  1  • 
structure  of  cicatricial  tissue  may  undergo  a  further  development,  i 
that  speeific  tissue-formations  eitlicM-  grow  into  it  seeojidariJ;/  or  are  present 
in  it  as  renudns  of  prd'.vistiug  sfrue'fures.  The  first  ])r<)<,'ess  occurs  nut 
frequently  in  scars  of  the  mucous  membrane  of  the  intestine  (Fig.  14  , 
and  of  glands  in  the  neighborhood  of  their  excretory  ducts,  and  in  sc;3 
of  muscle    (Fig,    145).     In  defects  of  mucous  membranes  which  se 


ki 


REGENERATION    AM)    HKl'AIH. 


2V 


replaced  by  scars  formed  tlirouoh  the  proliferation  of  conned ive  tissue 
(Fiji-.  144,  />,  /'),  the  surface  is  first  covered  with  epithelium  (//,  //,  A-), 

later  there  develop  epithelial  in- 
growths which  bear  the  character 
of  tubular  glands  (/).  Gland-ducts 
(bile-ducts,  ducts  of  the  salivary 
glands)  may  giowinto  the  develop- 
ing scar-tissue,  and  foi-m  new  tubes 
or  only  solid  cords  of  cells.  Such 
a  new-formation  of  gland-ducts 
may  occur  not  only  in  the  neigh- 
borhood of  traumatic  injuries,  but 
also  in  the  course  of  luematogenous 
inflannuations  of  the  glands  in 
question. 

A  new-formation  of  gland-t  issue 
proper  in  the  neighhorhoitd  of 
scars  is,  on  the  other  hand,  want- 
ing in  the  case  of  the  majority  of 
glands  (liver,  kidneys,  testicles, 
ovaries,  thyroid,  nuimmary  glands, 
and  lungs).  Only  in  the  case  of 
the  salivary  glands  does  the  de- 
velopment of  the  newly  foi-med 
ducts  lead  to  the  formation  of 
gland-lobules. 

In  muscle-scars  (Fig.  145)  new 
muscle -fibres  {d)  grow  from  the 
ends  of  the  old  ones  {a),  and  i)en- 
etrate  into  the  scar-tissue,  so  that 
the  scar  becomes  gradually  re- 
placed by  muscle. 

Tlie  preservation  of  remains  of 
specific  tissue-elements  in  the  area 
of  cicatrization  may  be  ol>seived 
in  the  case  of  both  muscles  and 
glands,  especially  in  the  periphery 
of  traumatic  injuries  aiul  auicmic 
necroses  (Fig.  14(j),  and  in  most 
cases  also  in  infectious  foci  of  dis- 
ease. Thepi-eser\ed  gland-remains 
within  the  scar  usually  ])res(Mit  an 
atrophic  condition  (I'^ig.  140,  h), 
but  islands  of  noinial  tissue  {(I) 
may  also  be  enclosed,  and  there 
arises  the  possil)ility  that  such  may 
undergo  a  comixMisatory  growth. 

In  inflammatory  ]»focesses  in 
glandulai"  oi-gans  Mhicli  aie  char- 
acterized on  the  on(;  han<l  by  the 
desti-uction  of  the  specitic  i)aren- 
chyma,  and  on  the  other  by  a  new- 
jormationof  connective  tissue  having  th(^  character  of  scar-tissue,  there 
lire  often  seen  in  the  diseased  area  new-formations  of  scar-tissue  cou- 


•''■'!  '■ 


'\  \ 


'  Fig.  lt.i.  -  sr:,,  .,i  ,.  ,, 
(lays  old  (Fl<-imnjnt.''s  s 
>ld  munch;;  /;,  tendon; 
luuscle-Bbres.    X  100. 

I 


'  '  II  'I  ■■  I,  l.>n.  tliirty-twii 
lutjiin,  \mii  (liesoii's).  o, 
c,  scar;  d,  newly  fDiiiied 


276  THE    PROGRESSIVE    CHANGES. 

taiuiiig  atrophic  remains  of  the  glaud-tissue,  and  between  these,  islands 
of  uninjured  gland-tissne  in  a  condition  of  hypertrophy. 

The  mass  of  the  scar  is  only  rarely  equal  to  the  mass  of  the  tissue 
lost,  and  tliere  persists  after  the  loss  of  considerable  amount  of  tissue  a 
more  or  less  marked  tissue  defect.  Over  circumscribed  areas  of  tlic 
surface  of  the  skin,  mucous  membranes,  or  of  glands,  the  brain,  etc. 
such  a  defect  gives  rise  to  a  cicatricial  depression.  Numerous  cicatricial 
defects  in  an  organ  may  occasion  an  atrophy  of  the  same  characterized 
bj^  an  irregular  configuration  of  the  surface. 

The  loss  of  the  tissues  en  masse  of  larger  portions  of  the  body,  as,  for 
example,  a  toe  or  a  toe-joint,  is  in  man  never  again  replaced.  Such  de- 
fects are  only  closed  in  by  scar-tissue  which  on  the  superficial  parts  of 
the  body  becomes  covered  Mith  surface  epithelium. 

The  regenerative  capacity  of  tissues  is  iu  man  and  the  mammals  slight  on  the 
•whole.  Tills  is  dependent  upon  the  fact  tiiat  the  individual  tissues  show  a  very  high: 
degree  of  differentiation,  and  that  also  in  the  event  of  proliferation  they  do  not  lose  this, 
differentiation  to  such  an  extent  as  to  revert  to  so  embryonal  a  state  that,  like  the  cells 
of  the  embryonal  anlage,  they  are  able  to  produce  different  forms  of  tissue.  In  spite 
of  this  limitation  the  regenerative  powers  of  the  tissues  in  general  are  sufficient  tc 
restore  the  continuity  of  the  tissues  and  to  preserve  intact  the  external  covering  of  th( 


^  'J/  -^fif^^^' 


FUJ.  146.— Peripheral  zone  of  an  embolic  scar  (Miiller's  fluid,  h;T?inatoxylin  antl  eosin).    a,  Scari 
ing  obliterated  glomeruli,  but  no  tubules  ;  ?»,  Indurated  tissue  with  atrophic  tubules,  the  glomeruli  beiiji 
c,  normal  cortical  tissue ;  (f,  island  of  normal  tubules  in  the  scar.     X  30. 


body.  If,  as  the  result  of  a  local  loss  of  tissue,  the  life  of  the  organism  be  endanger 
througli  the  inability  of  the  local  tissues  to  restore  the  lost  part,  there  exislsin  t 
case  of  many  organs^  and  tissues  (liver,  kidneys)  the  power  of  compensating  for  sucl, 
loss  through  the  growth  of  the  remaining  normal  tissue. 

In  tlie  lower  animals  the  power  of  tissue-regeneration  is  much  greater  than  in  1' 
case  of  the  mammals;  and  further  is  much  greater  in  the  earlier  stages  of  ontogene^ 
so  that,  in  many  animals  (tritons,  ascidians,  echinoderms,  teleosts).  the  first  two  or  cm 
the  first  four  segmentation  cells  still  possess  the  power  of  forming  an  entire  enibr. 
Insects  possess  dining  tJie  larval  state  a  very  marked  power  of  regeneration,  wh  » 
later  is  lost. 

In  the  case  of  protozoa  each  animal  may  quickly  supplement  itself  through  di  - 
6ion.  In  the  case  of  the  fresh-water  polypi  small  fragments  of  the  body  may  deve  ) 
again  into  the  entire  animal.  The  angle-worm  is  able  to  replace  either  'its  tail  or  h<  i 
enil  when  tliese  itre  cut  off'.     The  wood-louse  can  replace  its  feet  and  anteunte,  the  si  1 


REGENERATION    AND    UKPAIJi.  277 

its  tentacles  and  anterior  extremity,  crabs  and  craytisli  tluir  claws  iiiul  legs.  Salaman- 
ders are  able  to  restore  their  legs,  eyes,  and  tails,  and  li/.ards  and  slow-worms  tlieir 
tails,  when  these  arc  broken  off.  In  the  case  of  fmus,  snakes,  and  tishes,  on  the  other 
baud,  the  jiowcr  of  reiicneration  diminishes  as  tlie  .scale  of  ainnial  life  is  ascended,  yet 
this  does  not  happen  cqnally  in  the  case  of  all  animals,  and  animals  closely  related"  to 
each  other  may  show  very  different  capacities  for  regeneration.  Further,  in  the  same 
anin)al  the  regenerative  power  is  not  the  same  in  all  organs;  for  example,  in  tritons  tlie 
regeni'rativc  capacity  of  the  internal  organs  is  slight.  .Moreover,  the  i)owcr  to  form  a 
new  portion  of  the  body,  as  a  tail  or  extremity,  for  example,  docs  not  prove  that  all 
the  tissues  of  the  portion  of  the  body  in  question  ])ossess  an  esjiecial  capacity  for  ])ro- 
litVration.  In  crayfish  and  crabs  the  regeneration  of  the  claws  and  legs  takes  place  only 
from  certain  plaies;  in  injuries  occurring  to  other  points,  the  new  extremity  is  thrown 
olf  only  at  that  place  where  a  new-formation  is  jiossible.  In  tritons,  fractures  of  the 
bones  heal  very  slowly,  although  they  are  able  to  reproduce  tlieir  extremities. 

§  79.  The  cause  of  the  ceIl=proliferation  underlyinjj:  all  hyperplastic 
i;iiul  iv^eiu'iative  new-formations  of  tissue  varies  aceordino-  to  the  eoiidi- 
itions  under  which  the  proliferation  occurs.  If  the  new  ti.ssue-j;r()wth 
[leading  to  hypertrophy  takes  its  origin  from  the  anhige  of  the  orgtmism 
iconcerned  or  of  a  portion  of  the  same,  no  new  stimulus  is  necessary  for 
its  appearance;  the  attainment  of  the  abnormal  size  is  dependent  only 
iiipon  the  condition  that  the  new-formatiou  of  tissue  does  not  lead  to 
liindrances  to  growth  before  the  full  limit  of  development  is  reached. 
\\'lieu  the  proliferation  appears  first  at  a  later  period,  something  addi- 
tional is  necessary  to  cause  an  increase  of  the  normal  tissue-formation  or 
to  .'^tart  again  into  activity  the  cell-proliferatiou  which  becomes  quiescent 
at  tlie  close  of  the  period  of  growth. 

i  In  the  case  of  both  hyperplastic  and  regenerative  ])roliferat ion  the 
f  stimulus"  may  consist  simply  in  the  removal  of  hindrances  to  growth. 
Experience  teaches  that  the  majority  of  the  cells  of  the  body  po.s.sess  the 
power  in  a  given  case  to  divide,  even  those  (connective-tissue  cells,  gland- 
cells,  muscle-celhs)  in  which  the  processes  of  cell-division  Miiolly  cea.se 
for  long  jieriods  of  time.  This  cessation  of  i^roliferation  may  be  ex- 
[)laiiied  by  the  assumption  that  the  firm  combination  of  the  cells  with 
each  other  and  the  formation  of  the  intercellular  cement  inhibit  furthcj 
inultiplication.  It  is  also  possible  that  chemical  and  unknown  vital 
intiuences  act  in  the  same  manner.  Injuries  and  degenerations  of  the 
tissues  of  the  most  varied  kinds  can,  through  the  loosening  of  the  cells, 
and  through  physical  and  chemical  changes  in  the  intercellular  cement 
;^ubstaIlce  and  of  the  tissue-fiuids,  cause  such  changes  that  all  hindrances 
to  the  growth  and  division  of  cells  are  removed. 

I  In  addition  to  the  removal  of  hindrances  to  growth  there  may  be 
;|>Tesent  at  the  same  tinn^  a  formative  stimulus,  which  increases  both 
the  reproductive  capacity  and  the  tendency  toward  reproduction. 
Further,  such  a  stimulus  may  act  iii(le])eiidenlly — that  is,  without  the 
•removal  of  the  influences  inhibiting  growth — and  this  event  is  to  be 
issmned  in  those  cases  in  which  after  the  loss  of  a  ])()rtion  of  an  organ 
'he  remaining  i)ortion  (liver,  kidneyj  undergoes  a  compensatory  ii\  per- 
[.rophy. 

1  The  stimtdi  which  are  al)le  to  excite  growth  and  ccll-di\isioii  are 
fiiiown  only  in  part.  In  tho.se  cases  in  wliicii  their  action  may  be  n'cog- 
jUzed  they  apjiear  to  be  identical  with  the  stimuli  which  excite  or  increase 
functional  and  nutritive  activity.  In  the  case  of  tlu;  muscles  hyj)ertroi)liy 
is  brought  about  by  increased  contraction  following  nervous  excitation. 
jLiver  and  kidney  tissue  undergo  j^rol iteration  when,  as  the  result  of  a 
|Oss.of  a  large  area  of  gland-ti.ssue,  the  remaining  portions  are  obliged  to 


278  THE    PROGRESSIVE    CHANGES. 

do  an  increased  amount  of  work — that  is,  they  must  out  of  the  circulating! 
blood  produce  and  secrete  those  substances  which,  if  life  is  to  be  j)reserved,i 
must  be  given  off  either  externally  or  within  the  body. 

Whether  there  exist  still  other  formative  stimuli  cannot  be  said  wittill 
certainty  at  the  present  time.  An  increased  siipjjly  of  blood  and  nutrition,'  *^ 
which  has  been  believed  by  many  to  act  as  a  formative  stimulus,  is  nol: 
in  itself  sufticient  to  excite  a  new-formation  of  cells  and  tissue;  it  gives 
lise  only  to  an  increased  deposit  of  fat.  The  cells  of  the  body  are  noi 
fed,  they  feed  themselves ;  and  an  increase  of  nutrition  depends  uijon  tlu 
activity  of  the  cells.  An  increase  of  the  temperature  of  the  tissues  ma) 
hasten  the  process  of  cell-division  and  thereby  further  tissue-prolifeia 
tion ;  but  it  is  doubtful  if  it  can  directly  excite  proliferation  in  a  restint; 
tissue.  The  local  action  of  heat,  which  has  been  observed  to  be  followec 
by  proliferation  (for  example,  in  the  skin),  produces  in  the  first  placi 
changes  of  a  degenerative  nature,  so  that  tlie  occurrence  of  proliferatioii 
may  1)0  also  exi^lained  as  due  to  the  removal  of  influences  inhibitiu|: 
growth. 

Whether  there  are  chemically  active  substances  capable  of  exciting  pr(! 
liferatiou,  besides  those  present  normally  in  the  body,  cannot  be  decide; 
at  the  present  time.  The  fact  that  slight  irritation  of  the  skin  (paintin; 
with  iodine)  can  cause  proliferation  without  preceding  degenerativl 
changes  makes  this  appear  probable.  But  it  is  more  probable  that,  i| 
spite  of  the  negative  findings,  slight  tissue-changes  of  a  degene^ati^i 
nature  do  occur,  and  that  through  these  the  inhibitory  influences  aii 
weakened.  \ 

Moreover,  it  must  be  noted  that  even  the  hypertrophy  of  muscles  ari 
glands  following  increased  activity  cannot  be  absolutely  regarded  as  tlj 
direct  result  of  a  nervous  or  chemical  stimulus,  but  rather  must  v; 
assume  that  with  the  increased  labor  there  is  an  excessive  consumption  v. 
cell-elements  which  excites  regenerative  processes,  the  latter  leading  not  on' 
to  a  restoration  of  the  parts  lost,  but  also  to  an  increased  building-up  ^ 
the  cell -mass  and  formation  of  new  cells. 

Literature. 

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(•(■iluluires  les  mis  sur  les  autres.     Arch,  de  med.  exp.,  1890;  La  speciticite  eel  ■ 

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Bai'furth:  Ziir  Regeneration  de.-  Gewebe.     Arch.  f.  nn'kr.  Anat.,  37  Bd..  1891;  Regn- 

(•ration  d.  Keind»UUtor  bei  Amphibien.     Anat.  Hefte,  Wiesbaden,  1893;  Reirenet- 

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iH'llierenil.rvoiien.      Handb.  d.  Entwickelungsl.,  iii.,  1903. 
Beneke  :  Die  I'Vsudien  der  Thrombusorgaiiisalion.     Beitr.   v.  Ziegler,  vii. ,  1890. 
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de  biol.,  xxvi.,  1896. 
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lor,  v.,  1889. 
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REGENERATION    AM)    HKl'AIH.  279 

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med.  Woch.,  lOoO. 

See  also  §§80-87. 


280 


THE    PROGRESSIVE    CHANGES. 


§  SO.  The  division  of  the  nucleus  and  ceIl=body,  iipou  which  process 
the  formation  of  new  tissue  depends,  may  occur  in  the  first  place  through 
holoschisis  (Flemmiug),  or  direct  segmentation  (Arnokl) — that  is, 
through  a  trans\-erse  constriction  of  tlie  ehjngated  nuck'us  and  proto- 
plasm without  an  increase  or  characteristic  grouping  or  movement  of  the 
chromatin  elements  of  the  nucleus.  It  appears,  however,  that  the  direct 
division  of  the  nucleus  leads  to  a  new-formation  of  tissue — that  is,  to  the 
jiroductiou  of  cells  which  are  able  to  form  uew  tissue — only  when  it  is 
connected  with  that  form  of  cell -division   known   as  karyokinesis  or 


FIG.  147 


Fig-  149. 


Fig.  147.— Enlarged  nucleus.    Increase  in  the  chroniatin  framework. 

Fig.  14«. —Thick,  open  skein,  with  segmentation  of  the  threads  into  chromosomes ;  the  nucleolus  and 
nuclear  membrane  have  disappeared. 

Fig.  149.— Grouping  of  the  completed  chromosomes  into  a  star-  or  wreath-form. 


karyomitosis  (Flemming)  or  as  indirect  segmentation  (Arnold),  which' 
is  characterized  by  an  increase  of  the  nuclein  or  chromatin  (Flemmiug), ! 
and  a  definite  cycle  of  changes  of  form  and  movements  on  the  part  of  the  latter.  \ 

Usually  karyomitosis  follows  atypical  course,  as  in  the  normal  growth 
of  tissue,  but  deviations  from  this  are  not  infrequently  seen  in  pathologi- 
cal new-formations. 

A  resting  necleus  consists  of  an  outer  covering,  the  nuclear  membranr, 
and  the  nuclear  contents.  The  latter  is  composed  of  a  colorless  nuclear 
fluid  aud  the  nuclear  substance.  To  the  nuclear  substance  belong  the  ?m-j 
cleolus  and  scattered  granules  and  threads  which  often  form  a  framework] 
staining  with  nuclear  stains.  I 

When  the  nucleus  undergoes  division,  there  usually  occurs  in  the! 
first  place,  an  increase  of  the  chromatin,  and  the  chromatin  frameworh, 
becomes  more  distinct  (Fig.  147).  The  nuclear  substance  then  forms  a.i 
close  skein,  which  with  the  disappearance  of  the  nuclear  membrane  audi 
the  nucleolus  becomes  changed  into  an  open  skein  with  thick  threads  (Fig. 
148),  whose  individual  components  divide  themselves  into  nuclear  seg- 
ments (Hertwig)  or  ehromosomes  (in  man  these  number  eighteen)  (Figs. 
148,  149). 

These  segments  then  group  themselves  in  the  equatorial  plane  of  the, 
iHicleus  with  their  angles  directed  toward  the  centre,  forming,  wher! 
viewed  ('i-om  the  ])olar  asjjcct,  a  wreath-like  figure  (Fig.  149),  and  lateii 
a  stai-lik<!  ligni-e,  Ixiiig  in  the  equatorial  plane,  which  has  been  desigi; 
nated  the  mother-star  (Figs.  150,  151),  or  the  equatorial  plate  fFlem' 
ming). 

Sooner  or  later  two  poles  become  visible  in  the  so-called  polar  field- 
that  is,  two  extremely  small  spherules,  which  are  known  as  the  jwlar  oi 
central  corpuscles  or  the  cent rosomes.     At  first  these  lie  closely  together 


KARYOKIXESIS. 


281 


but  later  sepaiate  from  oiicli  other  and  act  as  centres  about  which  the 
nuclear  elements  oroup  themselves.  Between  these  there  is  formed  the 
nuch'iir  spindle  (Fiii's.  152,  15,'})  which  consists  of  tine  threads  wliich  do 
not  stain  with  nuclear  stains,  and  converge  in  tlie  polar  corpuscles.     In 


^A 


<$m 


Fl( 


Fk;.  I.V.. 


Fig.  150.— Completely  developed  mother-star ;  polar  view. 

Fig.  151.— Mother-star ;  equatorial  view. 

Fig.  152.— Stage  of  metakinesis.    Single  loops  visible,  their  angles  pointed  toward  the  pole  ;  delicate 


spindle-flgure  within  the  nucleus. 

Fig. IW.— Daughter-star;  side  view  (nucleus  barrel-shaped); 
radial  arrangement  of  protoplasm  are  visible. 


spindle-flgure  in  the  nucleus  and  the 


)       Fig.  154.— Daughter-stars  separated :  the  upper  one  presenting  polar  aspect,  the  lower  one  a  side  view. 

1        Fig.   15.5.— Daughter-skein  with  fine  threads  (above),  and  with  lattice-work   (below).    Completed  di- 
j  vision  of  the  protoplasm. 


!the  nei{2:hborhood  of  the  polar  corpuscles  themselves  the  granules  of  the 
•protoplasm  present  a  radial  arrangement,  giving  rise  to  figures  (Fig. 
153)  which  are  known  as  r<ii/-fif/ureH,  stars,  or  atlrariion-splwrrs.  In  the 
Tollowing  stage  of  division  of  the  nucleus,  a  movement  takes  place  among 
tlie  cliromosdmes  leading  to  the  formation  of  loops,  mIiosc  angles  are 
directed  toward  the  pole.  Later  the  loo])S  divi(h>  in  halves  whi(di,  follow- 
■  iiig  the  direction  of  the  spindle-fibres,  move  towaid  the  ])oles  and  form 
'two  stars  (Figs.  152-154)  Mhich  are  known  as  <hni(//itrr-.stor.s.  From  tiie 
I  star-figures  the  daughter-star  passes  successively  through  the  thick-skein 
Jvndthen  the  fine-skein  stage  (Fig.  155,  upper  part)  wliich  finally  changes 
into  the  nuclear  framework  (Fig.  155,  lower  part).  During  the  later 
{.stages of  the  process  of  division  a  new  nuclear  membrane  is  formed. 

In  the  stages  of  the  segmented  skein,  or  later  as  may  lie  seen  in  the 


282 


^HE    PROGRESSIVE    CHANGES. 


larjie  nucleated  cells  of  cold-blooded  animals,  there  occurs  a  Jongitudinal 
splittiuff  of  the  chromosomes  (Fig.  156).  In  the  change  of  position  of  the 
chromosomes  known  as  metakinesis  the  halves  of  the  split  threads  sepa- 


i 


Fig.  156.— Mother-star,  with  chromosomes  split  longitudinally.    (Alter  Rabl). 

Fk;.  157.— Metakinesis.    The  halves  o'  the  chromosomes  are  separating  from   each  other  and  turning" 
toward  ihe  poles.     (After  Rabl. i 


rate  from  each  other  (Fig.  157)  so  that  each  daughter-star  receives  halli  I; 
of  the  substance  of  each  chromosome. 

The  division  of  the  cell=protoplasm  usually  takes  place  at  the  tim( 
the  daughter-star  changes  into  the  ordinary  nuclear  condition,  and  con 
sists  in  a  constriction  and  separation  of  the  protoplasm  (Fig.  155).  I 
is  probable  that  a  complicated  interrelationship  exists  between  the  uucleii: 
and  cell-protoplasm;  but  the  nucleus  is  to  be  ref;arded  as  the  more  h'ujhh 
organized  substance,  as  the  centre  of  ceJJuJar  potent ialitii.  The  nueJei  are  als>l 
the  bearers  of  herediti/,  while  the  protoplasm  governs  the  relations  of  th<j 
cell  with  the  outer  Morld. 

Variations  from  tlie  typical  karyokinesis  may  consist  in  the  firs 
place  in  the  occurrence  of  ii  pJurlpolar  division  in  place  of  the  bipolar,  s 
that  two  to  six  or  more  nuclear  spindles  and  a  correspondingly  increasf 
number  of  equatorial  plates  (Fig.  158,  a)  may  be  formed.  Further,  i 
place  of  the  simple  mother-star  there  may  be  formed  a  complicated  figui 
out  of  the  chromatin  loops,  from  which 
several  daughter-stars  may  be  evolved. 
Not  infrequently  there  occur  asymmetncal 
divisions  of  the  nucleus  (Fig.  158,  b,  c),  par- 
ticularly in  tumors,  but  occasionally  also 
in  regenerative  or  inflammatory  new-for- 
mations of  tissue. 

There  also  not  infrequently  occur 
divisions  of  the  nucleus  which  are  char- 
acterized by  abnormal  size,  abnormal  rich- 
ness in  chromatin,  and  manifold  variations 
of  form.  As  types  of  such  division  are 
the  lai'ge  oval  or  l)ean-shaped  (Fig.  159), 
kii()l)l)('d  or  convoluted,  lobulated  and 
branched    (Fig.     KiO),    wreath-shaped,  \ 

linked,  basket-shaped  (Fig.  1(51),  and  otherwise-shaped  nuclei.  Finall^i 
there  are  occasionally  found  in  the  cells  more  or  less  extensive,  iudi! 
tinctly-ontlined  heaps  of  granular  and  lumpy  chromatin  (Fig.  162).       | 


Fig.  ].V<.  — n,  Pluripolar  division-flgurijfv 
h,  c,  asymmetrical  division-flgures.        ||f- 


I 


ATYPICAL    CKLL- 1 )  n  I  SI  ( )  V. 


2S3 


Such  nuclear  forms,  with  the  excei)tiou  of  the  polynuclciirlcucocyles, 
are  found  ])arti('ularly  in  the  cells  of  tlie  bone-marrow,  spleen,  and 
lyinpli-.ulands,  and  also  in  tumoi-s  Avliich  arise  from  the  bone-marrow  or 
periosteum,  but  have  been  also  obserNcd  elsewhere,  ])arlicularly  in  sar- 
comata. Certain  of  these  forms  are  ai)peaiances  due  to  conliactiou,  and 
have  nothiuu'  to  do  with  cell-division.  In  <»thei- cases  llM'scchan^es  of 
size  and  form  precede  a  division  of  the  nucleus  throu.uli  conslricliou  of 
certain  portions,  this  process  occurrinji"  sometimes  m  itli,  sometimes  with- 
out an  increase  of  the  chronmfin-subslance.  Arnold  has  desi^natt'd  the 
division  by  constriction  with  increase  of  the  chromatin  as  imlhrct  J'nuj- 
mentation,  that  without  such  increase  as  direct  frdf/mentation.  Indirect 
fraguuMitation  diffei'S  f rom  mitosis  or  indirect  segnuMitat ion  in  the  lack 


'''yA'-i^\ 


Fig.  150.  Fig.  1611. 

Fig.  1.59.— Cell  with  oval,  slightly  knobbed  giant-nucleus,  rich  in  chromatin. 

Fig.  163.— Cell  with  lobulated  giant-nucleus.  Fk;.  161.— Cell  with  basket-shaped  giant-nucleus. 

Fig.  162.— Cell  with  large  masses  of  chromatin.    All  these  cells  from  a  sarcoma  of  bone.    (Stroebe, 
lieitriinc  von  Zityhr,  VII.) 


'-^'"^  "^"^ 


of  an  orderly  arrangement  of  the  chromatin  in  threads  and  in  the  irregu- 
larity with  which  the  separation  of  portions  of  the  chromatin  results  in 
uew  nuclei. 

Variations  in  the  division  of  the  cell-protoplasm  occur  most  fre- 
quently, either  in  a  total  failure  of  the  protoplasm  to  diride  after  the  divi- 
sion of  the  nucleus  has  taken  place,  or  in  the  delayed  divi.s'ion  after  that 
of  the  nucleus.  These 
phenomena  are  ob- 
served in  both  mito- 
tic and  amitotic  divis 

I  ion    of    the    nucleus, 

'  an<l  lead  to  the  for 
Illation  of  multinu- 
clear     giant  =  cells 

1  (Fig.  Hi'.lt,  which  are 

I  designated    as    plas- 

!  modial  giant=cells. 
Cells  (.f  the  .spleen 
and  hone-manow  and 

\  of  tumors  arising 
from  the  bones  show 
this  phenomenon  with 
especial  frequency. 
Proliferating  fat-cells 
likewise    often    form 


/ 


i -;,..' 


S  L2iS' 


:.V.i;'r  .5 ..... O^ 


'V5|Mi«.\'W«vWV'V 


Fig.  163  —Proliferating  adipose  tissue  from  the  subcutaneous  pannic- 
iilns,  twcntv-six  days  after  cauterization  with  trichloracetic  acid  (forma- 
lin, ha-matoxvlin).  o,  Multinuclear  fat-cells;  /»,  proliferating  connec- 
tive tissue.     X  301). 


284  THE    PROGRESSIVE    CHANGES. 

multiiuK'lear  fjiant-cells  (Fig.  163,  a).  Besides  this  form  of  ninltinnclear 
giant -cell  there  also  occur  those  formed  by  the  conliuenee  of  cells,  which 
are  known  as  syncytial  giant=cells.  (Compare  also  the  sections  on 
luflammation  and  Tuberculosis. ) 

The  significance  of  the  nuclear  corpuscles  (nucleoli)  is  still  a  matter  of  dispute. 
Flemming  and  Pfitzner  believe  that  they  are  different  from  the  nuclear  framework, 
while  others  regard  them  as  much-thickened  nodal  points  of  the  fibrils  of  the  frame- 
work. In  what  way  they  are  again  formed  after  the  division  of  the  nucleus  is  not 
kno^\'n. 

The  spindle-figure,  whose  fibres  stain  but  slightly  with  nuclear  stains,  is  derived, 
according  to  Flemming  and  Hertwig,  from  the  achromatic  substance  of  the  nuclear 
framework,  while  Strasburger  believes  that  it  arises  from  the  cell-protoplasm. 

The  centrosomes  or  polar  corpuscles,  which  are  always  present  in  nuclear  segmenta- 
tion, are  found  also  in  resting-nuclei;  but  up  to  the  present  time  they  have  been  demon- 
strated only  in  a  part  of  the  cells,  most  frequently  in  lymphocytes  and  the  giant-cells 
of  the  bone-marrow.  At  the  same  time  the  investigations  of  von  KoUikcr,  Flemming, 
M.  Heidenhain,  Boveri,  and  others  make  it  probable  that  the  centrosomes  are  present 
in  all  cells,  lying  sometimes  in  the  nucleus,  sometimes  in  the  protoplasm,  where  on 
account  of  their  small  size  they  can  be  demonstrated  only  with  difficulty.  (The  cen- 
trosomes do  not  stain  with  the  ordinary  nuclear  stains,  but  with  acid  aniline  dyes,  as 
acid  fuchsin,  safranin.  and  with  iron-'haematoxylm.)  Whether  they  are  elements  of 
the  protoplasm  or  of  the  nucleus  has  not  yet  been  decided.  According  to  ran  Bene- 
den,  Boveri,  and  Rabl,  the  mitosis  of  the  nuclear  substance  is  to  be  referred  to  a  direct 
dra wing-apart,  starting  from  tlie  divided  centrosomes  and  brought  about  by  the  agency 
of  the  achromatic  fibres.  According  to  M.  Heidenhain,  the  central  corpuscles  are  sharply 
circumscribed  granules  which  possess  the  power  of  assimilation,  of  growth,  and  of  multi- 
plication by  budding,  whereby  they  are  accustomed  to  form  groups.  Either  alone 
or  united  in  groups,  they  can  form  the  central  point  of  insertion  of  a  system  of  con- 
tractile fibres  (spindle-figures,  microsome  rays),  and  consist  of  a  specific  substance  (in 
a  chemical  sense)  which  is  not  present  elsewhere  in  the  cell. 

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i 


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Schwarz:  Zur  Theorie  der  Kerntheilung.     Virch.  Arch.,  124  Bd.,  1894. 
Strasburger:  Zellbildung  u.  Zelltheihuig,  Jena.  1890;    Ueber  den  Thpilungsvorirang 

der  Zellkerne  u.  d.  Verhaltniss  der  Kerntheilung  zur  Zelltheilung.     .\rch.  f.  mikr. 

.\nat.,  xxi.,  1882;   Die  Controversen  d.  indirecten  Kerntheilung.     lb.,  xxiii.,  1884; 

Das  Protopla.sma  u.  die  Reizbarkeit,  Jena,  1891. 
Stroebe:  Kerntheilung  u.  Riesenzellenbildimg  in  Geschwiilsten  u.  iiu  Knochenmark. 

Beitr.  v.  Ziegler,  vii.,  1890;  Cellulare  Vorgange  u.  Erscheinungen  in  GeschwuLsten. 

lb.,  xi.,  1891;    Vorkommen  und  Bedeutung  der  asymmetrischen  Karyokinesen. 

lb.,  xiv.,  1893. 
Verworn:   Die  phvsiolog.   Bedeutimg  des  Zellkerns.     Pfluger's  Arch..  51  Bd.,  1892. 
Waldeyer:  Ueber  Karyokinese.     Deut.  med.  Woch.,  1886,  1887. 
Weismann:  Das  Keinipla.sma,  .Jena.  1892. 

Wilson:    I'he  Cell  in  Development  and  Inheritance,  New  York.  1897. 
Zander:  Ueber  d.  gegenwiirt.  Stand  der  Lehre  v.  d.  Zelltheilung.     Biol.  Cl)l..  xii.,  l.S<)2. 
Ziegler,  H.  E.:  Biologische  Bedeutung  der  amitoti.schen   Kerntheilung.     Biol.   Cbl., 

xi.    1.S91. 

II.  The  Processes  of  Hyperplasia  and    Regeneration   in   the   Various 

Tissues. 

i?  SI .  The  morphological  chansos  in  ilu'  regeneration  and  hyperplasia 
of  epithelium  are  relatively  siniide.  The  kaiyoinitosi's  (  I'^i;;.  Di4,  ad) 
show  for  the  chief  x)art  a  typical  course.  Tlie  division  of  the  prolopla.sni 
takes  place  either  in  the  later  stages  of  the  process  of  nuclear  dixi.sion  or 


286 


THE    PROGRESSIVE    CHANGES. 


4 'A 


follows  after  the  same.     Giant-eells  may  arise  through  failure  of  the 
protoplasm  to  divide. 

Epithelium  arises  only  from  epithelium,  and,  moreover,  the  ditfereut 
varieties  of  epithelimu  do  not  pass  over  into  one  iwiother.  It  is  to  he 
noted,  howe\'er,  that  under  certain  conditions — for  example,  in  cases  of 
inflammatory  iiritation  of 
long-  standing — the  regen- 
erating epithelium  may 
change  its  character,  so 
that  pavement  epithelium 
may  occasionally  be  de- 
veloped in  places  which 
originally  possessed  strat- 
ified ciliated  columnar 
epithelium.  This  may 
occur,  for  exam^ile,  in  the 
case  of  cicatrization  of 
ulcers  in  the  trachea.  De- 
fects of  ciliated  columnar 
epitlielium  are  in  the  first 
place  repaired  by  low  col- 
umnar or  flat  cells  which 
later  become  changed  into 
high  columnar  cells. 

Small  losses  of  substance  in  the  superficial  epithelium  are  usually 
quickly  replaced  through  regenerative  growth  of  the  neighboring  cells 
(Fig.  ios,  d,  d^,  fZJ.  In  such  cases  it  may  be  seen  that  the  epithelium 
bordering  upon  the  defect  quickly  pushes  over  the  denuded  surface  and 
begins  to  proliferate.  The  division  of  the  nucleus  and  cell -protoplasm 
takes  place  not  only  on  the  edge  of  the  defect,  but  also  at  some  distance 
from  it.  In  the  intestine  the  loss  of  the  superficial  epithelium  is  quickly 
made  good  by  a  proliferation  of  the  epithelial  cells  situated  in  the  deep 
parts  of  the  crypts  of  Lieberkiihn.  Likewise  glandular  epithelium — : 
for  example,  in  the  liver  or  kidneys — is  quickly  restored  after  loss,  pro- ; 
vided  the  structure  of  the  tissue — that  is,  of  the  basement  membrane  i 


Fig.  164.  —Regenerative  proliferation  of  tin'  epitlielium  of 
bile-ducts,  in  tlie  neighborhood  of  a  wound  c  if  the  liver  live  davs  old 
(Fleuiming's  solution,  safranin).  a.  Enlarged  nuiJeus  of  epi- 
thelial cell,  with  increase  of  chromatin ;  b,  epithelial  cell  with 
mother-skein ;  c,  epithelial  cell  with  mother-star ;  d,  epithelial 
cell  with  daughter-skein ;  /,  connective-tissue  cell  with  daughter- 
star.    X  400. 


t.L^ 


Sf 


<?. 


V 


;■    - •  -  ■         'i 

Fio.  li;r>. —Healing  of  blister  caused  by  a  burn  (alcohol,  alutn-carinine).  Section  through  the  skin  of; 
cat  s  paw,  forty-(!ight  hours  after  the  production  of  a  blister,  a.  Horny  layer :  b,  rete  Malpighii ;  c.  coniiiii 
((,  newly  formed  epithelium ;  d,,  f/^,  newly  formed  epithelium  already  differentiated  into  different  layers 
t ,  old,  degenerated  epithelium ;  /,  pus-cells  ;  (/,  exudate ;  /i,  sweat-glands.    X  ~'5. 


uixni  Mhich  it  rests— is  not  changed.     After  destruction  of  liver-tissut 
both  liver-cells  and  the  epithelium  of  the  bile-ducts  (Fig.  104)  prolif 


REGENERATIOX    OF    KPITIIKLUM.  287 

rate,  aud  the  cell-divisiou  attendant  ii[)on  an  injury  to  the  liver  may 
xtend  to  a  relatively  great  distance  from  the  wound.  Experimental 
»vonnds  of  the  liver  heal  through  the  toiinalion  of  eonneetive  tissue,  into 
;vhieh  only  otfshoots  of  the  bile-duels  luMict  lalo,  while  a  local  icprodue- 
. ion  of  liver-tissue  does  not  tak«»  place.  Likewise,  in  llie  kidneys,  testi- 
•les,  thyroid,  and  ovary  the  local  ])i-oduction  of  glandular  tissue  in  the 
'onneclive-tissue  scar  is  very  slight  <^»r  wholly  wanting,  and  does  not 
ead  to  the  fonnatiou  of  fuiu'lionating  tissue.  In  the  salivaiy  and  mu- 
ii'ous  glands,  on  the  other  hand,  there  occurs  a  branching  of  the  gland- 
lucts,  and  a  new-formation  of  glandular  alveoli. 

I  When  portions  of  the  mucosa  and  subniucosa  of  the  intestine  are  lost 
IS  a  result  of  ulcerative  processes,  there  occuis  during  the  process  of 
lealing  a  glandular  proliferation,  which,  accoi-ding  to  the  natr.re  of  the 
ilefect,  forms  partly  typical,  partly  atypical  (Fig.  144,  /)  glands  which 
ii'ow  into  the  submucosa.  The  new  gland-foiniation  takes  its  start  fiom 
he  old  glands,  whose  epithelium  pushes  over  the  edge  and  base  of  the 
i.ilcer  (Fig.  144,  g,  li)  and  also  lines  any  depressions  which  may  hai)pen 
!:o  be  present  (A).  In  a  similar  manner  ulcerative  defects  of  the  stomach 
:uucosa  are  again  made  good;  and  even  extensive  ulcers  may  become 
♦overed  over  with  a  gland-containing  mucosa,  although  the  glands  do 
lot  for  the  most  part  show  a  typical  development — that  is,  are  not  trans- 
I'ornied  into  characteristic  gastric  glands. 

The  epithelial  portions  of  the  nteriue  mucosa  Avliich  are  in  part  lost, 
IS  a  physiological  process,  during  menstruation  and  paituiition,  and  are 
d'terward  replaced,  maybe  restored  in  a  similar  manner  in  the  healing 
tf  pathological  defects  of  the  endometrium.  The  new-formation  of  epi- 
helium  takes  its  origin  from  the  glandular  remains. 

j  Compensatory  hypertrophy  of  a  kidney  or  liver,  as  the  result  of  the 
I  OSS  of  kidney-  or  liver-tissue,  is  brought  about  through  t\w  formation  of 
[leio  (fJund-ceUs,  and  the  enlargement  of  existing  renal  tubules,  ov  lirer-rods 
■r.sprrtiveJi/.  After  extirpation  of  one  kidney  the  beginnings  of  comi)en- 
>atory  hypertrophy  are  recognizable  even  on  the  third  day,  by  the  ap- 
•earance  of  division  figures  in  the  epithelium  of  the  urinary  tul)ules; 
uid  theie  then  follows  a  further  proliferation,  continuing  for  some  time, 
|jf  the  epithelium  of  the  uriniferous  tubules  and  glomei-uli  as  well  as  of 
he  cells  of  the  vessel-walls,  as  a  result  of  which  all  the  ])arts  become 
Milarged.  In  the  liver  the  lobules  are  enlarged,  but  no  new-formation 
jf  these  occurs. 

Literature. 

{Kewfornudion  of  EpitheJium  and  Gland- Tissue.) 

^.dler:  Helle  (junge)  Zellen in  der  Leber.    B.  v.  Ziegler,  xxxv. ,  1903. 

A.rnold:  Epitlielregeneration.     Vircli.  Arcli.,  46  Bd.,  1869. 

ftLSColi:  Fonuiiz.  della  mucosa  gastria.     A.  per  le  So.  ^Med.,  xxv.,  1901. 

Barbacci:  Kigeneraz.  fisiol.  degli  elemeuti  epiteliali.     Aicli.   ])er  \r.  Sc.   Mcil.,  xiii., 

1SS',( 

7.  Bardeleben:  Die  Heilung  der  Epidermis.     Virch.  Arcli.,  10:5  Bd.,  1901. 

Bizzozero:  Regen.  d.  Drusenzellen.  Vircli.  Arch.,  110 'Bd.;  Arch,  per  Ic  Sc.  Med., 
xi.,  1S87;  Die  schlauchformigeu  Drliseii  d.  Magendarmkaiials.  Arch.  f.  mikr. 
Anat.,  82  Bd.,  1893. 

Bockendahl:  Regen.  v.  Flimmerepitliel.     Arch.  f.  mikr.  Anat.,  xxiv.,  188r)._ 

Bossi:  IJcprod.  de  la  muqueuse  de  I'uterus.     Arch.  ital.  de  Biol.,  xxiv.,  1895. 

^oen:  Vcriindorungen  der  Ilaut  nadi  der  Einwirkung  von  Jodtinctur.  Beitr.  v.  Zieg- 
ler, ii. :  Zur  Anatomie  der  Milclidriise.     lb.,  ii.,  1887. 

3oene  D'Ajutolo:  Sulle  alterazioni  istologiciie  dei  reni,  dei  miiscoli,  dello  stomaco, 
degli  intestiui  e  del  fegato  uel  avvelenamento  cronico  di  piombo.  Beitr.  v.  Ziegler, 
iii.,  1888. 


288  THE    PROGRESSIVE    CHAXGES. 


Cornil  et  Carnot :  Regen.   cicatricielle  des  conduits  muqueux.     Arch,  de  med.  exp.,  fB*^; 

X.,  1898;  Keg.  des  cavites  muqueuses.     lb.,  xi.,   1899;  Cicatrisat.  des  plaies  du  ^^f' 

loie.     Sem.  med.,  1898. 
Fuckel:    Regeu.    d.    Submaxillar-    u.    Infraorbitaldrilsen.      Inaug.    Diss.,    Freiburg, 

1S96. 
Flemming:    Regen.  v.  gescbicbt.   Piattenepitbel,   Darmepilhel  u.  Flimmerepitbel  des 

Eileiters,  Foriikelepilbel  des  Ovarium.     Arch.  i.  mikr.  Auat.,  xviii.,  xxiii.,  xxiv., 

1880-85. 
Golg-i,  C. :  Xeoformazione  dell' epitelio  dei  cauajicolioriniferi.     Arch,  per  le  Sc.  Med.. 

vi.,  1881;  Arch.  ital.  de  Biol.,  ii.,  1882. 
Griflani:    Contribut.  alia  patol.  del  tessuto  epitel.  cilindr.,  Torino,   1884;   Arch.  ital. 

de  Biol.,  v.,  1882;  Sulla  riproduzione  parziale  del  testicolo.     Arch,  per  le  Sc.  Med.. 

xi.,  1887;  Sulla  riproduzione  degli  organi  gustatori.     Rendiconti  dell'  Istituto  Lom- 

bardo,  1887. 
GriflBni  u.  Vassale:  Ueber  d.  Reproduction  d.  Mageuschleimhaut.     Bcitr.  v.  Ziegler, 

iii..  1888. 
Hochhaus:    Gewebsveranderungen  nach   Kalteeinwirkuug.     Yirch.   Arch.,   154  Bd., 

isys. 
Jatta:  Rigen.  dell'  epitelio  del  rene.     Arch,  per  le  Sc.  Med.,  xxi.,  1897. 
Jung-;  Reg.  d.  Uterusschleimhaut  nach  Verletzung.     Cbl.  f.  Gyn.,  1897. 
Kahn:  Etude  sur  la  regeneration  du  foie,  Paris,  1897. 
Karg-:  Studien  liber  trausplantirte  Haut.     Arch.  f.  Anat.  u.  Phj-s.,  1888. 
Mall  :  Ilculing  of  Intestinal  Sutures.     Johns  Hopkins  Hosp.  Rep.,  i.,  1887. 
Mayzel :  Tlieilung  der  Kerne  in  Epithelzellen.    Cbl.  f.  d.   med.  Wiss.,  1875. 
V.  Meister  :  Recreation  des  Lebergewebes.     Beitr.  v.  Ziegler,  xv.,  1894.  ; 

Morpiirgo  :  Zellneubildiuig  wilhrend  der  Inanition.     Beitr.  v.  Ziegler,  i v.,  1889.  i 

Neese  :  Verhalten    d.  Epithels  bei  Heilung  v.   AVundcu   d.  Hornhaut.      v.    Graefe's 

Arch.,  xxxiii.,  1887. 
Petrone  :  Du  proc.  regen,  sur.  le  poumon,  sur  le  foie  et  le  rein.     Arch.   ital.  de  Biol, 

v.,  1882. 
Piccoli  :  Rigenerazione  parziale  della  prostata.     Arch,  per  le  Sc.  ]\Ied.,  xxiv.,  1900. 
Pisenti  :  Sur  la  cicatrisation  du  rein,  etc.     lb.,  vi.,   1884. 

Podwyssozky  :  Regen.  der  Drliseugewebe.  Beitr.  v.  Ziegler,  i.,  il.,  1886-87. 
Poggi  ;  La  cicatrisation  immediate  des  blessures  de  Testoraac.  lb.,  iii.,  1888. 
Ranvier :    ]Mecanisme  de   la  cicatrisation.      Lab.  d'histol.    du    College    de    France, 

I'.KIO. 
Ribbert:  Regeneration  der  Mammilla.     Arch.  f.  mikr.  Anat.,   37  Bd.,   1891;  Reg.  v. 

Liber  u.  Nieren.    A.  f.  Entwickeluugsmech.,  xviii.,  1904.  | 

Sanfelice  :  Regeneration  du  testicule.     Arch.  ital.  deBioL,  ix.,  1888.  fj 

Schlatter:  Traumat.  Leberverletzungen.     Bcitr.  v.  Bruns,  xv.,  1896.  I 

Simanowsky  :  Reg.  d.  Epithels  d.  Stinunbandes.     Arch.  f.  mikr.  Anat.,  xxii. 
Stroebe  :  Acute  Leberatrophie.     Beitr.  v.  Ziegler,  xxi.,   1897. 
Tarchetti  :  Regen.   d.  Hautdriisen  bei  Triton.     B.  v.  Ziegler,  xxxv.,  1904. 
Tizzoni  :  La  hsio-patologia  dell'  epitelio  pavimentoso  stratiticato.    Arch.  ital.  de  Biol.,' 

vi.,   1884. 
Vossius  :  Regen.  d.  Epithels  der  Cornea,     v.  Graefe's  Arch.,  xxvii.,  1881.  f 

Wath:   Kegeneration  d.  Uterusschleimhaut.     Arch.  f.  Gyn.,  49  Bd.,  1895.  _     , 

Wentscher :    Epidermismitoseu  in   exstirp.    Hautstiicken.      B.    v.    Ziegler,    xxxiv..' 

\'.m. 

Werner:  Experimentelle  Epithelstudieu.     Beitr.  v.  Bruns,  xxxiv.,  1902. 
Wolff:  Die  Xierenresection  u.  ihre  Folgen,  Berlin,  1890;  ref.  Virch.  Arch.,  161  Bd. 
V.  Wyss  :  Eiiillnlre^a-neration.     Virch.  Arch.,  69  Bd.,  1877. 

Ziegler:  Uisachen  d.  jiathoL  Gewebsneubildungen.     Intern.  Beitr.,  Festschr.  f.  Vir 
chow,  ii.,  Berlin,  1891. 

§  82.  Tho  new=formation  of  blood-vessels  plays  a  very  iniportau' 
role  in  hyperplasia  of  the  most  varied  tissues.  If  connective  tissue! 
bone,  or  glandular  tis.sue  is  to  be  reproduced  in  any  considerabl! 
amount,  the  new-formation  of  blood-vessels  is  essential,  since  it  is  onl;  *. 
through  these  that  sufficient  nutrition  can  be  brought  to  the  growiu' 
tissue. 

The  development  of  new  blood-vessels  takes  place  tlirough  the  forma, 
tion  of  offshoots  from  the  sides  of  the  walls  of  ]ireexisting  vessels  (Fi.tJ 
HW).     In  the  vessel-wall  there  occurs  a  proliferation  of  cells,  particu 


I 


NEW-FOEMATIOX    OF    liL()()I)-\  KSSKLP,,  2,S0 

larly  of  the  endothelium    (Fi--.    ir,7),    in    AvliicU    the   division    <.f   tlie 
niu'lous  occurs  l»y  karyomitosis. 

•  As  tlie  lirst  stop  in  llic  lonnation  of  ;i  now  vessel,  thei'e  is  seen  on  tlie 
fouter  side  of  some  capillniy  loop  a  tent-like  elevation  which  tenninates 
linatine  protoplasmic  thread  (Fig.  166,  a),  standing  out  from  the  vessel, 
land  gradually  becoming  longer  and  longer,  while  the  granular  mass  like- 


I  Fig.  166.— Development  of  blood-vessels  by  formation  of  offshoots;  from  preparations  taken  from  In- 
Iflammatory  granulations,  a,  b,  c,  d.  Different  forms  of  offshoots,  some  solid  (b,  c),  others  becoming  hol- 
!low  (a, /»,(?),  some  simple  (a,  d),  some  branching  (/>,  c),  some  without  nuclei  U(,  d),  some  vvilli  nuclei 
Hh,  c);  </,  offshoot  to  which  flbroblasts  have  applied  themselves. 

[wise  grows  out  at  the  same  time.  There  is  thus  formed  at  the  beginning 
ja  solid  (jmnuJar  arch  of  protoplasm,  loliich  ends  in  a  protoplasmic  thread  (ci), 
and  after  a  certain  time  comes  to  contain  nuclei.  This  thread  may 
penetrate  into  another  vessel,  or  may  nnite  with  some  other  arch  which 
;it  meets,  or  finally  may  return  to  the  same  vessel  from  which  it  started. 
I  Further,  from  the  solid  arch  itself  new  secondary  arches  may  spring 
i(Fig.  UU],  b,  c),  or  at  its  end  there  maybe  foinied  a  club-shaped  swell- 
iing  (<•). 

;  The  originally  solid  arch  becomes  hollow  after  a  ceitain  time  (/>,  ^0 
through  the  licpiefaction  of  its  central  part,  and  the  space  thus  foi-med 
either  immediately  or  very  soon  comes  to  communicate  with  th<>  lumen 
.of  the  blood-vessel  (a),  or  else  there  is  developed  from  within  the  vessel 
jjui  extension  of  the  vessel-lnmen  into  the  arch.  The  blood  of  the  mot  her- 
Ivessel  finds  its  way  at  once  into  the  cavity  of  the  daughter-vessel  and 
widens  it.  As  the  hollowing-out  process  constantly  advances  and  ex- 
l<'ii(ls  to  the  point  of  entrance  of  the  proto])lasmic  arch  into  another 
blood-vessel,  there  is  finally  formed  a  new  cai)illary  loop  jx-iineable  for 
blood. 

I      Immediately  after  the  opening  of  a  way  for  the  blood  tiie  ca|)illaiy 
tube  ])ossesses  a  homogeneous  wall.     After  a  certain  length  of  time  the 
protoplasm  groups  itself  about  the  nuclei,  which  have  in  the  mean  time 
19 


290 


THE    PROGRESSIVE    CHANGES. 


divided  and  multiplied  in  tlie  wall,  so  that  ultimately  tlie  capillary 
comes  to  be  made  up  of  flatteued  endothelial  cells.  As  Arnold  has 
shown,  the  boundaries  of  the  individual  flattened  endothelial  cells  may 
be  made  visible  through  the  injection  of  a  solution  of  silver  into  the  ves- 
sel. At  this  time  the  wall  for  the  greater  part  appears  much  thickened, 
partly  from  the  x>roliferatiou  of  the  cells  of  the  A'essel-wall,  but  also 
partly  from  the  fact  that  formative  cells  from  the  neighborhood  heap 
themselves  upon  the  surface  of  the  young  vessel  (Fig.  166,  d),  adapt 
themselves  to  the  wall,  and  so  strengthen  it. 

At  the  time  of  the  formation  of  the  offshoots,  the  endothelial  cells  of 
the  capillaries  are  swollen,  so  that  they  form  cells  rich  in  i>rotoplasm, 
which  often  in  proliferating  tissues  reach  such  a  size  that  the  cross-sec- 
tion of  a  capillary  looks  not  unlike  a  ^and-tube  lined  with  epithelium 
(Fig.  168,  d).  At  the  same  time  di\ision -figures  appear  in  the  endo- 
thelium (Fig.  167,  a-c),  and  later  the  division  of  the  nucleus  and  cell- 
protoplasm  takes  place. 

Just  in  what  relation  this  proliferation  stands  to  the  formation  of  the 
offshoots  is  not  yet  clearly  understood ;  but  doubtless  the  latter  spring 
fj'om  proliferating  cells  and  represent  cell-proc- 
esses of  the  same.  The  proliferation  of  endothe- 
lium, on  the  other  hand,  does  not  always  lead  to 
a  new-formation  of  vessels,  but  may  result  only 
in  a  thickening  of  the  vessel-wall  and  finally  in 
an  obliteration  of  the  lumen. 

In  the  transformation  of  newly  formed  capil- 
laries into  arteries  and  veins — a  change  which 
must  always  occur  in  the  case  of  extensive  new- 
growths — the  inci'ease  of  tissue  is  the  result  of  the 
continued  proliferation  of  the  cells  of  tlie  vessel - 
wall.  The  muscle-fibres  first  appearing  in  the 
outer  wall  of  the  capillary  tube  are  (Mayer)  finely- 
branched  cells  whose  nuclei  lie  i^arallel  to  the  long 
axis  of  the  capillary  and  whose  processes  surround 
the  endothelial  tube.  After  about  fourteen  days 
elastic  fibres  may  also  appear  in  new-formed  ves- 
sels (arteries). 


It  is  difficult  to  decide  whether  the  neir-formaiion  of 
llood-Vi'ssels  is  iutracellular  through  the  hollowing  out  of 
the  solid  buds  of  a  siugle  cell  or  whether  it  is  intercel- 
lular through  the  formation  of  a  space  between  two  cells. 
The  olfslioots  from  the  sides  of  the  vessel-wall  or  from  the 
end  of  the  vessel  give  the  impression  of  solid  cell  proc- 
esses, but  the  possible  participation  of  the  protoplasm  of  two  cells  in  the  forniatio, 
of  such  processes  cannot  be  excluded. 

The  neic-formatioii  of  lymph-vebsds  in  new  connective  tissue  is  intercellular. 


Fir.  167.— Two  vesselsof  th 
papillary  body,  whose  endol 
thelial  ot>lls  are  in  process  oj' 
priilifi-nuiou  Nix  days  afte 
paiiitiuL'-  till-  bnck-  of  the  foe 
Willi  tinrtiiiv,.fi(  .(line)  {Fleir 
niintr's  sulutidii,  siafranin.an 
pii^ric  aciil).  <(,  Nucleus  wit 
chromatin  framework  :  h,  h 
skein- ff)rms;  r.  mother-star 
d.  connective-tissue  cell  wit 
nuclear  division-tlgure 
lymphocytes.    X  350. 


Literature. 

(Xew-fonuatioii  of  Blood-i^esseJs.) 

Arnold:    Die  Entwicklung  d.  Blutcapillaren.     Yircli.   Arch.,   53  Bd.,   1871;   54 

1^7-2. 
Billroth:  riitersuch.  fiber  die  Entwickelung  der  Blutgefiisse,  Berlin,  1856. 
Coen:   N'ciiind.  d.  Ilaut  nach  Einwirkuug  von  Jodtinciur.     Beitr.  v.  Ziegler,  ii.,  1 
Flemraing':  Theilung   von   Pigmcntzellen   u.    Capillarwandzellen.     Arch.    f.    mifc; 

Auat.,35Bd.,  1890. 


y 


xp:w-foh.mati()x  of  coxxectivk  tissip:.  201 

Fiichs:  Zur  Pliys.  ii.  Wiichstiinisnu'clianik  d.  Gi'fiisssy stems,  Jena,  1902. 

Kuborn  :   DevHoj)]).  dcs  vaisscaux  duns  Ic  io'v  dc  I'cmbryon.     Anat.  Anz.,  v.,  1890. 

Mayer:  Muskulaiisierung  dvr  Kapillarcn.     Anat.  Anz.,'x.\i..  1902. 

Maximow  :  Kntziindl.  Neubild.  v.  Bindcs^ewcbe.    B.  v.  Ziegler,  Supp.  v.,  1902. 

Nothnagel :  Die  Eutstchuug  des  Collateral kreislau Is.     Zeitscbr.  1'.   kliu.  Med.,  xv., 

is>y. 
Ranvier  :  Traite  technique  d'histologie,  187(5. 

Talke  :  J^yniphgefiissneubildung  in  pleurit.  Seliwartcn.    V>.  v.  Zicgler,  xxxii.,  1902. 
Thiersch":  Handbk.  d.  Chir.  von  v.  Pitliau.  Billrotb,  ii. ;  Arch.  f.  klin.Chir.,  xvii.,  1874. 
Thoma  :  llislogenese  unci  Histoniechanik  des  Gctasssystenis,  Stuttgart,  1893. 
Yamagiva:  EutzAindliche  Gefassneubildung.      Vircli'.  Arch.,  132  Bd.,  1893. 
Ziegler  :  Ueber  pathologische  Bindegewebs-  und  Gefassneubildung,  Wi'irzburg,  1870. 

^  83.  The  connective=tissue  structures  are  almost  all  capable  of 
botli  liyperplastic  and  ivi;enei'ative  proliferation.  This  is  especially  true 
of  unformed  and  foi-med  connecuve  tissue,  the  periosteum  and  the  end- 
osteuni ;  while  cartilage  possesses  but  a  slight  regenerative  capacity, 
and  fully  developed  bone  none  at  all.  Usually  proliferating  fibrous  con- 
nective tissue  gives  rise  to  fibrous  tissue,  both  in  the  case  of  independ- 
ent formations  of  connective  tissue  and  in  the  supporting  tissue  of  the 
glands,  lungs,  lymph-glands,  and  brain.     The  periosteum,  bone-niairow, 

perichondrium     and      cartilage 
4<T-^-v-  'tjT  ,.-^  -^  ^"--c::-^;;^::^    >»         producc   in    addition  to  fibrous 
"  "^  -'^^•z  connective  tissue   and  marrow- 


•^■^  ,®  ^,    -          *      ^^^fx""  tissue  also  cartilage  and  bone. 

a^  "  '     s  ^-^  ^  ^"^4>^©^                  Hyperplastic   and    regener- 

^^y  ^       '^   ir^r^^^^Jl^^  ative  proliferations  of  the  con- 

*-0'  -^    ■"-  ^^  ^  ^^'.^^^^e  iiect i ve  tissues  are  ushered  in  by 

""zC"  ^ —  ,   »^  "'    ^'^-^^l^T  rr//-<//r/V/o«  in  the  course  of  which 

i^  ^^       :     ^^^   ^>A^  the    karvomitoses,    described 

5i£  .^^    --*.^;7      ;M^«^t  ^^'^'-   ^'^^"^''  ^^"'  ^^' 

^^  .€3   ^^^-^^  1<^'^.  ^.  e),  occur. 

^,'  -m^J^y^::^  ^^J^  After  injuries   of   the  tissue 

yy       '■  these  proliferations   begin    very 

Fir.,  liis.— prclifi-ratiiiir  perid^feiim,  four  days  after       SOOU,   aS,  for  example,  iu  '.VOUUds 
fractiirrof  :i  ix  me  (Flfiiiuiinfr's  solution,  lia?matoxylin).  '     .  •        ^        ^  e 

,1.  (isi.-,,i,iii,-ts  with  UiiKc  nu.-h-i;   /-,  osteoblast,  with     of  the  SKiu,   Or  111  Iractures  OI 

(liviMnii-tlixiirf;    c.    two    cells   shortly    after   division,  fU^     hnnps;  •      in     t1w»  l-iftiM-    <"Wi> 

showinsr  thread-skein  In  nucleus;  t/,  blood-vessel  with  '"^     uones ,     in     ini.  i.li  u  i     t  .ist 

proliferatinsr   endothelium;   e,   endothelial   cell   with  even   aS   Carlv  aS  the  Second  dav 
nui-lear  division-figure ;/,  larpre  lymphocytes;  (/,  siuall         .       ,            n      "    /-     ^i  •      . 

lymphocytes.   X  ^50.  "       '  Single   cells   ot    the    i)eriost('iiin 

have  become  enlarged  and  show 
division-figures.  Besides  mitoses,  direct  division  of  the  nuclei  also  takes 
place. 

\Mieu  only  a  few  cells  are  destroyed  in  the  event  of  an  injury  to  the 
'tis.sue  newly  formed  cells  replace  those  destroyed  without  the  occuri-ence 
lof  any  marked  structural  changes  in  the  tissues.  If,  on  the  other  hand, 
under  pathological  condition.s,  a  considerable  amount  of  new  tissue  is 
]»rodii('ed  within  a  short  time,  the  i)roliferating  cells  form  an  embryonic 
tissue  consi.sting  essentially  of  ceils,  blood-vessels,  and  a  somewhat  libril- 
Uited  ground-substance  (Fig.  168).  The  extent  of  such  fornuition  nat- 
urally varies  greatly  and  is  dei)endent  partly  upon  the  capacity  of  the 
tis.sue  for  i)roliferation,  and  partly  upon  tlw^  lesi(»n  leading  to  the  }»rolif- 
eration. 

Proliferating  cells  are  always  larger  tlian  the  cells  of  fully  develo])ed 
and  resting  connective  tissue  which  are  relatively  ])ooi'  iu  protoi)lasm. 
They  contain  large,  bladder-like  nuclei  Avilh  nucleoli,  and  for  the  greater 
part  only  oneor  two  nuclei  (Figs.  1<)8,  109),  though  mult  inueiear  cells 
(Fig.  1G9,  c  j,  the  so-called <//««^ce/As',  also  occur.     In  association  Mith  the 


292 


THE    PROGRESSIVE    CHANGES. 


enlarged  tissue-cells  there  are  always  fouud  after  a  more  marked  tissue 
lesion  exudative  cells  arising  from  the  blood- ves;  Is  (Figs.  168,  r/,  /,  and 
169,  a,  (ij  which  take  no  part  in  the  formation  of  the  new  tissue  (see  §  95). 
Since  all  these  cells  are  the  antecedents  of  the  future  tissue  they  are 
designated  as  formative  cells,  those  giving  rise  to  fibrous  connective 


#x::^-^ 


Fig.  169.— Isolated  cells  from  a  granulating  wound  (picrocarmine) .  a.  Lymphocyte;  «,,  poljmucleai 
leucocytes ;  /),  dilTerent  forms  of  mononuclear  fibroblasts ;  c.  formative  cell  with  two  nuclei ;  c„  multi 
nuclear  formative  cells;  d,  fibroblasts  in  stage  of  connective-tissue  formation;  e,  fully  developed  con 
uective  tissue.    X  500. 

tissue  are  called  fibroblasts  (Figs.  169,  h,  c,  d.  e;  170,  a),  while  thos< 
forming  cartilage  and  bone  are  known  as  chondroblasts  (Fig.  172,  «,  c 
and  osteoblasts  (Fig.  168,  a,  h,  c)  respectively. 

The  shape  of  the  formative  cells  varies  greatly  (Fig.  169,  b,  c,  d,  e) 
and  is  dependent,  partly  upon  intrinsic  causes — that  is  upon  spontaueoui 
changes  of  form — partly  upon  the  influence  of  the  environment,  whicl 
under  certain  conditions  compels  the  cells  to  take  certain  definite  formsj 
The  cells  producing  connective  tissue  usually 
present  the  greatest  variety  of  form. 

AVhen  connective  tissue  is  developed 
from  a  cellular  embryonic  tissue,  either  fine 
fibrilhe  (Fig.  169,  d,  e)  appear  at  once  in 
certain  parts  of  the  cell -protoplasm,  or  there 
is  formed  first  a  homogeneous  interceUulur  sub- 
stance (Fig.  170,  h)  in  which  the  fibrilloe 
later  appear.  The  formative  cells  at  the 
same  time  diminish  in  size,  and  come  to 
lie,  for  the  most  part,  in  small  clefts  (Fig. 
169,  e)  in  tlie  ground-substance. 

Elastic  fibres  first  appear  in  newly 
formed  connective  tissue  at  a  late  stage, 
altout  three  weeks  at  the  earliest,  and  at  the  beginning  form  very  fi' 
fibrillar,  which  in  ])art  (Fig.  171,  b)  represent  processes  of  older  thick' 
fibrillar  {a)  and  in  part  arise  independently.  They  represent  a  diff<- 
entiation  product  of  the  fibrillary  ground-substance  and  have  no  relati  i 


■'X    - 


Ficf.  170.— Development  of  conn, 
five  tissue  from  fibroblasts  (Miille 
fluid,  picrocarmine).  a,  Fibroblas 
/(,  hyaline  ground-substance  w 
scattered  fibriUse ;  c,  fibroblast  w 
adjacent  fibres.    X  400. 


lii 


NEAV-FOKMATIOX    OF    ]U)\K    AM)    (  A IMI  l.A(;  K 


29:i 


to  the  cells.      In  so  fai-  as  can  be  (Iclciniiiicd,   Ihcy   -.uv  ruiiiu'd    llnoiiuii 
the  union  of  small  i;ranuk's  of  clastic  substance. 

They  develop  most  abundantly  in  ncAvly  formed  connective  tissue  in 
the  blood-vessels  and  in  the  skin,  but   such  a  new-format  ion  of  elastic 


Fig.  171.— Scar  of  tbe  skin,  two  years  old,  showing  newly  formed  elastic  fibres  (alcohol,  orcein),    a,  Ce- 
rium with  normal  elastic  fibres ;  b,  scar  with  newly  formed  elastic  fibres.    X  oUO. 

fibres  occurs  also  in  other  regions,  as,  for  exami^le,  in  connective-tissue 
proliferations  inside  of  glands,  serous  niembi-anes,  etc. 

Ill  the  develoi^nient  of  hyaline  cartilage  there  appears  between  the 
cells  a  hyaline  basement-substance  (Fig.  172,  /),  while  the  chondrohJafits 
(»  at  the  same  time  assume  a  more  rounded  form  (</).  In  time  the 
ground-substance  increases,  the  chondroblasts  grow  smaller  and  come  to 
lie  in  rounded  cavities  whose  walls  are  denser  than  the  rest  of  theground- 


'^^Ml^ 


d, 


m^ 


-'^i-'- 


^.i, 
% 


Fig.  172.— Periosteal  formation  of  cartilase  in  a  fracture  fivednvs  old  fFlemiiiin«'s  soluticn,  lurinn- 
M>xylln  glycerin).  «,  Cellular  embryonic  tissue  :  /-,  cartiiajre;  c,  proliferatlnjr  iicriost.-ul  rlinuilrolilasls; 
".  cartllajfe-cells ;  r/,.  c/^,  nuclear  division-figures  in  cartilage-cells;  c,  ground-substance  of  (•iiibryiinl<i 
tissue:  /,  ground-substance  of  the  cartilage;  o,  capsule  of  cartilage-cells ;  /i,  prulireraling  endotheliuni  of 
a  blood-vessel.    X  330. 


substance  and  later  form  the  part  of  the  basement -subst: 
\c(niilaf/r-rap.sHh'  fy). 

In  the   development  of    bone  from   cell n la r   en 
I  appears  between  the  formative  cells  a  dense  homo 


lied  the 


Inyoiiic   t  issue  thei-e 
eneous  or  iibrillated 


294 


THE    PROGRESSIVE    CHANGES. 


basement-substance  (Figs.  173,  e,  f ;  174,  c)  forming  an  osteoid  tissue 
which  later  on  becomes  impregnated  with  lime-salts  and  thereby  trans- 
formed into  bone.     When  the  ground -substance  between  the  osteoblasts 


/  ^^^.^^i:^C  >^WW 


Fig  ]7  5  — Ir  iidusti  <il  foiinatiou  i)f  bone  from  masses  of  osteohl  ist>«  (Miilh  i  s  fliii  1  pk  nc  aciti,  haema-  ] 
toxyliii,  cdriiiine)  Pieparation  from  tbe  inner  oillu>i  of  a  fount  i  n  Inillfii  lun  of  tlie  tlbula  of  a  man  i 
twenty  11\  e  >  ears  of  ij?e  <i  hat-cells  of  the  tmlosteum  .  h,  end  -ii  mn  c  mi  uniii/  no  fat,  (  s(  ittered ! 
osteoblasts  ,  d,  jrroups  of  osttoUl  ists  ,  (  first  step  in  tlu  form  itioii  c  1  ilie  ^lound  NulMatu  (  of  bone  ,  /,  de-' 
veloping  tr.ibec  iildD  of  bone  ,  </,  livei  of  osteoblasts  hing  ui)onili».  nt\\l\  foiuud  iiabnule  of  biine;?J,; 
blood  \(,ssel      X  150.  ; 

i 

is  already  of  a  loose  fibrillar  nature  (Fig.  173,  d)  the  transition  into 
osteoid  tissue  is  brouglit  about  through  a  thickening  of  the  ground-sub- 
stance (e, /).  The  osteoblasts  come  to  lie  in  irregular  spaces  furnished 
with  processes  (Figs.  174,  c;  175,  h),  and  are  then  usually  known  as 
hone-corpuscles.     In  extensive  development  of  cellular  embryonic  tissue' 


Fig.  174.— Formi 
fourt+'en-day  old  fiac 
outer  pi-riosteuin  ;  /), 


trabecular  from  ttie  proliferatin<r  periosteum.  Preparation  from 
Mid.  picric  acid,  lueinatoxyliii,  cjirmine).  a.  Fibres  belonging  to  tl 
ic;  c,  o.steoid  ti.ssue  ;  (/,  cartilage  :  c,  bone-uiarrow.     X  75. 


the  change  into  bone  is  limited  to  certain  parts  of  the  tissue,  so  thi' 
within  the  embryonic  tissue  trabecuhe  (Fig.  174,  c)  are  formed,  whicl 
so  long  as  they  do  not  undergo  full  development  into  bone  and  do  n- 


XEW-FOR^NIATIOX    OF    TUK    COX  MX  TIN  H    TlSSi   KS.  '2\)') 

become  calcified,  are  called  osteoid  trabeculse.     The  embryonic  tissue 

(b)  lying  betNveeu  becomes  chaiii;ed  into  marrow-tissue  by  the  cells  be- 

U'cmiui;"  united  to  each  other  tluouj;h  ])roccsses,  wliih'  between  them  there 

appears  a  tluid  basement -substance,  in  wiiich  rcumd-cells  later  appear 

1  embedded.     If  only  ii  little  bone-tissue  is  to  be  formed  and  dei)osited 

i  upon  old  bony  trabecuhe,  the  o.stcohla.stH  (Fij;-.  175,  c)  arian-ie  themselves 

upon  the  surt'ace  of  the  latter,  and  these  later  on  proihice  bone  (h)  in  tlie 

manner  described  above,  which  appears  as  a  new  bony  hinielhi. 

Fibrillated  connective  tissue,  bone,  and  cartilaj^e  are  closely  related 
I  to  each  other  and  one  may,  theiefore,  be 

'     K--.  ^  -^^%<^'^^'-^.^^^g       easilytransformedintothe()ther(seei?SS). 
r^  ^?S  •®  %  <^ ;^-  .:ii^ -, *?■ -t^.  ^i  Mucous  tissue  arises  from  embryonic 

//        "*■         »*        ""         ^     *       tissue  throuii'li  the  foiniation  of  a  muciu- 
^  ;         containing,  homogeneous,  ji'elati nous  Ijase- 

ment-substance  between  the  cells  m  liicli  at 
/^      least  in  part  become  united  through  proc- 
esses to  foiin  a  netwoik. 
--  *      — _"  Lymphadenoid    tissue    can    develop 

Fiu.  175. -Fonnatu.ii  of  bone,  through      from  embrvouic  tissue  tlirougli   the   foi'- 

dpposits  niatle  liv  osteoblasts  upon  the  sur-  _  .    "^  ^ .  /  •       i  /. 

faceofourooneCMuUer's  fluid,  picric  acid,      matiou  01  a  Supporting  reticulum  1  roiii  a 
SS"d  S!":Uob?al'' xl(i':      part  of  the  cells,  while  lymphocytes  gather 

ill  the  meshes  of  this  network,  the  spaces 
I  of  which  contain  lymph.  In  injured  Ijpnph-f/Jands,  the  cells  of  the  relic- 
I  ulum  proliferate  and  form  onliiKO-i/  Jihrou.s  ti.ssiic ^  a  reticular  develop- 
1  ment  of  this  connective  tissue  into  lymphadenoid  connective  tissue  either 
i  does  not  take  place  at  all  or  but  to  a  very  slight  degree. 
[  Spleen=tissue  is  not  formed  anew  after  injury  to  this  organ;  the 
!  wound  heals  through  ordinary  cicatrization.  Compensatory  liy])(Mtrophy 
I  does  not  take  iDlace  after  the  removal  of  large  portions  of  the  organ. 
j  Fat=tissue  arises  through  the  taking  up  of  fat  into  the  cells  of  em- 
)  bryonic  tissue,  mucous  tissue  or  fibrous  connective  tissue,  the  cells  be- 
j  coming  changed  into  fat-cells  through  the  conflueuce  of  the  fat  droplets 
I  which  they  take  up. 

i  The  basement=substance  of  th.3  tissues  described  al)OM!  is  a  product 
;  of  the  protoplasm  of  the  formative  cells.  AVhether  in  its  formation 
portions  of  the  cell-protoplasm  are  changed  directly  into  interc(»llular 
I  substance,  or  whether  they  secrete  the  latter,  or  separate  it  from  the  in- 
!  tercellular  fluid,  is  often  a  difficult  question  to  answer;  but  it  is  piobable 
'  that  only  the  first  two  methods  of  formation  occur. 

Fibrillar  connective  tissue  can  develop  from  any  of  the  connect i\<>  tissues  possess- 
j  ing  the  power  of  proliferation,  but  there  must  first'be  formed  an  intciinediate  stage  of 
I    embryonic  tissue. 

!  Bone  arises  chiefly  from    the    periosteum,  perichondriimi,  and    endosteum,  but 

1    may  also  develop  from  other  connective-tissue  substances,  as,  for  example,  from   the 

I    intemmscular  connective  tissue  and  from  the  connective  tissue  of  the  bhxxl-vessels. 

i  Cartilage  arises  chiefly  from  proliferating   ijericiiondriiun,  periosteiun,  ciKhjsteum, 

and  cartilage  itself;   but  may  also  be  develoj^ed  from  other  connective  tissues,  as,  for 

example,  in  the  connective  tissue  of  the  testicle  and  parotid.     Tiie  cartilnge-cclls  neara 

lesion  may  imder  certain  circumstances  proliferate  and  form   a  large-celled  embryonic 

tissue,  but  this  does  not  reach  any  great  size.     In  the  proliferation  of  cartilage-cells 

[    within  Girtilage  the  cell-multiplication  and  new-formation  of  cartilage  occur  in  the  same 

way  as  in  the  physiological  proliferation  of  tliis  tisstie.      \'ery  often  the  newly  formed 

cartilage  is  only  a  transitory  tissue,  and  is  so(mi  transformed  ag.iin  into  Ixme  and   mar- 

.    row-tissue,  or  into  connective  tissue. 

•  New  hi  in  ]>h  adenoid  tissue  may.  under  pathological   conditions,  arise  either  from 

!    lymphadenoi.l  tissue  or  fat-tissue  (Bauer)  or  from  fiiirill.ilcd   connective  ti.ssue.     It  is 
I    formed  from  the  latter  most  frequently  in  the  connective  tissue  of  the  mucosa  and  sub- 


1 


296  THE    PROGRESSIVE    CHANGES. 

mucosa  of  the  intestinal  tract,  as  well  as  in  the  glandular  organs;  rarely  in  the  inter- 
muscular connective  tissue.  New  hsemolymph-nodes  are  formed  in  adipose  tissue 
after  splenectomy  {Warthhi). 

Mucous  iissiie  may  develop  from  any  proliferating  connective-tissue  substance,  but 
rarely  appears  in  large  masses,  and  is  usually  a  transitory  form  passing  over  either  into 
fat  or  connective  tissue. 

Fat-tissue  develops  particularly  in  those  regions  normally  containing  fat,  but  oc- 
curs also  at  times  in  other  places,  for  example,  in  the  reticular  connective  tissue  of 
atrophic  lymph-glands,  in  the  perimysium  internum  of  atrophic  muscles,  etc. 

The  close  relationship  of  the  connective-tissue  substances  to  each  other  enables  the 
different  fonns  to  pass  from  one  to  another  without  the  need  of  an  intermediate  stage 
of  embryonic  tissue  produced  by  proliferation.  Further  details  in  regard  to  this  point 
are  contained  in  §  88. 

Literature. 

(Neic-for-mation  of  Connective-tissue  and  Elastic  Fibres.) 

i 
Bernheim:    Entw.  d.  elast.  Fasern  in  d.  Lunge.    Jahrb.  d.  Hamburger  Krankenanst., 

vii.,   1902. 
Borst:   Heilungsvorgange  nach  Sehnenplastik.     B.  v.  Ziegler,  xxxiv.,  1903. 
Busse:   Heilung  asept.  Wunden  der  Haut.     Virch.  Arch.,  134  Bd.,  1893. 
Dmitrijeff:    Verand.  d.  elastischen  Gewebes  b.  Arteriosklerose.      Beitr.  v.  Ziegler, 

xxii.,  1897. 
Fischer:    Exper.  Unters.  tib.  d.  Heilung  von  Schnittwunden  d.  Haut.     Inaug.-Diss.,     i 

Tiibingen,  1888. 
Flemming;    Histogenese  d.  Bindesubstanzen.    Handb.  d.  Ent'wickelungsl.,  iii.,  1902. 
Gardner:    Histogenese  d.  elastischen  Gewebes.     Biol.  Cbl.,  xvii.,  1897. 
Graser:  Feinere  Vorgange  bei  Verwachsung  peritonealer  Blatter.     Zeit.  f.  Chir.,  xxvii. 

1888. 

Grohe:   Bedeutung  d.  elast.  Fasern.     Miinch.  med.  Woch.,  1901. 
Hamilton:   On  the  Presence  of  New  Elastic  Fibres  in  Tumors.     Trans.  Chicago  Path.. 

Soc,  1900. 
Hansen:    Tienese  einiger  Bindegewebegrundsubstanzen.     Anat.  Anz.,  xvi.,  1899. 
Homen:   Regeneration  der  fixen  Hornhautzellen.     Fortschr.  d.  Med.,  i.,  1883. 
Jores:    Xeubildung  elast.  Fasern.     Beitr.  v.  Ziegler,  xxiv.,  1898;    xxvii.,  1900. 
Kromayer:   Regen.  d.  elast.  Fasern  in  Hautnarben.     Monatsh.  f.  Derm.,  xix.,  1895. 
Levi:    Einfl.  v.  Zug  auf  d.  Bildung  faser.  Gew.     A.  f.  Entwickelungsmech.,  xviii.,  1904. 
Lwoff:    Entwickelung  d.  Fibrillen  des  Bindegewebes.     Wiener  Sitzber.,  98  Bd.,   1889. 
Mall:    Developm.  of  the  Connective  Tissues.     J.  of  Anat.,  i.,  1902. 
Maximow:    Entziindl.  Neubild.  v.  Bindegewebe.     B.  v.  Ziegler,  Suppl.  v.,  1902. 
Melnikow:   Unters.  lib.  d.  elastischen  Gewebe.     Beitr.  v.  Ziegler,  xxvi.,  1899. 
Merkel:  Histogenese  d.  Bindegewebes.     Verh.  d.  anat.  Gesellsch.,  v.,  1896. 
Minervini:   Ausbildung  der  Narben.     Virch.  Arch.,  175  Bd.,  1904. 
Neumann :     Entwickelung  d.   Bindegewebes  in   pleuritischen   Schwarten.     Arch.  d. 

Heilk.,  1869. 
Nikiforoff:    Bau  u.  Entwickelung  des  Granulationsgewebes.     Beitr.  v.  Ziegler,  viii.,  ] 

1890. 
Oliver:    Elastic  Tissue  in  Cirrhosis  of  the  Liver.     Trans.  Chicago  Path.  Soc,  1902.  _ 
Passarge  u.  Krosing:  Regen.  d.  elast.  Gew.  d.  Haut.     Derm.  Stud.  v.  Unna,  xviii.,  i 

1894. 
Pearce:   The  Increase  of  Elastic  Tissue  in  the  Lung  in  Chronic  Congestion.     Jour,  of 

Med.  Res.,  1901. 
Podwyssozki:    Regeneration  der  Driisengewebe.     Beitr.  v.  Ziegler,  i.,  ii..  1886-87.     ! 
PoljakofP:   Anat.  d.  Bindegewebes.     Arch.  f.  mikr.  Anat.,  45  Bd.,  1895. 
Ranvier:   Mc'canisme  de  la  cicatrisat.     Lab.  d'histol.  du  College  de  France,  1900.  ' 

Schaffer:   (irundsubstanz,  Intercellularsubstanz.     An.  Anz.,  xix.,  1901.  j 

Schiffmann:   Histogenese  d.  el  ist.  Fasern.     C.  f.  a.  P.,  xiv.,  1903.  j 

Seggel:   Heilung  von  Sehnenwunden.     Beitr.  v.  Bruns,  37  Bd.,  1902. 
Spuler:    Histogenese  der  Bindesubstanz.     Anat.  Hefte,  xxi.,    Wiesbaden,  1896. 
Teuffel:   Entw.  elast.  Fasern  in  d.  Lunge.     Arch.  f.  Anat.,  1902. 
Yamagiva:   Zellenstudien  an  sich  regenerirendem  Sehnengewebe.     Virch.  Arch.,  135 

Bd..  1894. 
Zachariades:   Tissu  conjonct.     Lab.  d'histol.  du  College  de  France,  1900.  __     ' 

Ziegler:   1 'ntersuch.  iiber  pathol.  Bindegewebs-  u.  Gefassneubildung,  Wiirzburg,  1876. 

See  also  Inflammatorj'^  New-formations  of  Tissue.  : 


XEW-FOmiATIOX     OF    Kin  TH  HOCVTKS.  297 

(Xeic-formafion  of  Ctotildf/r.) 

Bardeleben:    Knorpel.     Eulenburg's  Realencyklop..   189G. 

Ewetzky:    Entziindungsversuche  am  Knorpel.     Arb.  a.d.  jiathol.  Instit.  in  Ziirich, 

iii..   Leipzig,   1875. 
Gies:    Heilung  v.  Knorpehvunden.     Deut.  Zeitschr.  f.  ('hir..  xviii.,  1S82. 
Kassowitz:    Die  normale  Ossification,  etc.,  Wien.  1881. 
Lelas:    Reparat.  du  cartilage  articulaire.     A.  de  nied.  exp..  1902. 
Matsurka:^Regen.  de.s  Knorpelgewebes.     Virch.  Arch..  17")  Bd.,  1V>{)4. 
Peyrand:    Etudes  exper.  sur  la  regen.  des  tissus  cartilagineux  et  o.ssetix.  ISC)!). 
Schatfer:    Ban  u.  Eutwickl.  d.  Knorpelgewebes.     Z.  f.  wis.s.  Zool.,  70  Bd..  li)()l. 
Schleicher:    (Knorpelzelltheilung.)     Arch.  f.  mikr.  Anat.,  xvi. 
Schottelms :   Die  Kehlkopfknorpel,  Wie.sbaden,  1879. 
Sieveking:    Wachsthum  u.  Regen.  d.  Knorpels.     Morph.   Arl)eiten  v.  .Sch\vall)e,  ii., 

1S9I. 
Solger:    Feber  Knorpelwachsthum.     Fortschr.  d.  Med.,  vii.,  1889. 
Spiiler:  Ban  u.  Entstehung  d.  elast.'Knorpels.     Inaug.-Diss.,  Erlangen,  189.5  (Lit.). 
Srdinko:   Histologie  u.  Histogenese  d.  Knorpel.     An.  Anz.,  xxii.,  1903. 

j  (yew-fonnation  of  Boiw.) 

Barth:   Knochenimplantation.     Beitr.  v.  Ziegler.  xvii.,  189.5. 

Bonome:   Knochenregeneration.     Virch.  Arch.,  100  Bd.,  1885. 

Bruns:   Die  Lehre  v.  d.  Knoclienbriichen.     Deut.  Chir.,  Lief.  27,  Stuttgart,  1886. 

Kassowitz:   Die  normale  Ossification,  etc.,  Wien,  1881,  1882. 

KoUiker;  Die  normale  Resorption  des  Knochengewebes,  Leipzig,  1892;   Gewebelehre, 

1889. 
Krafft:  Zur  Histogenese  des  periostal.  Callus.     Beitr.  v.  Ziegler,  i.,  1886. 
Sacerdotti:   Heteroplast.  Knochenneubildung.     Virch.  Arch.,  168  Bd.,  1902. 
Troja:   Experiences  sur  la  regeneration  des  os,  Paris,  1890. 
Wolff:  Enters,  iib.  d.  Entwickelimg  d.  Knochengewebes,  Leipzig,  1874;  Virch.  Arch., 

101  Bd.,  1885. 
Ziegler:    Proliferation,  Metaplasie  u.  Resorption  d.  Knochengewebes.     Virch.  Arch., 

73  Bd..  1878. 
I         See  also  Pathological  Anatomy  of  the  Bones. 

(Format ioti  of  Lymphadenoid  Tissue  and  Spleen-tissue.) 

Bayer:  Regeneration  u.  Neubildung  der  Lymphdriisen.  Prager  Zeitschr.  f.  Heilk., 
vi.,  1885;    Ueber  kranke  Lymphdriisen.     Langenbeck's  Arch.,  49  Bd.,  1895. 

Ceresole:   Regeneration  de  la  rate.     Beitr.  v.  Ziegler,  xvii.,  1895. 

Czermak:  Entwickelung  d.  Lymphknotchen  d.  Darmwand.  Arch.  f.  mikr.  Anat.,  42 
Bl..  1893. 

Galland:  The  Development  of  Lymphatic  Cdands.     Jour,  of  Path.,  ii.,  London,  1894. 

Hiiter:  Heilung  nach  Resekt.  v.  Lymphdriisengewebe.  Verh.  d.  D.  path.  Ges.,  vii., 
1004. 

Laudenbach:   Totale  Milzregeneration.     Virch.  Arch.,  141  Bd.,  1895. 

Ribbert:  Regeneration  u.  Entziindung  der  Lymphdrusen.  Beitr.  v.  Ziegler,  vi., 
1889. 

Saxer:   Entwickelung  d.  Lymphdrusen.     Anat.  Hefte,  Wiesbaden,  1896. 

Stohr:  Die  Entwickelung  des  adenoiden  Gewebes.  Anat.  Anz.,  vi.,  1891;  Entwick- 
elung der  Darmlymphknotchen.     Arch.  f.  mikr.  Anat.,  41  Bd.,  1898. 

Warthin:  The  Changes  Produced  in  the  Hirmolympli  Nodes  of  the  Sheep  by  Splenec- 

;  tomy.  Jour,  of  Med.  Res.,  1902;  The  Relation  of  the  Haemolymph  Nodes  to  Adi- 
1         pcse  Ti.ssue.     Trans.  Phil.  Path.  Soc,  1903. 

Zehnder:  Ueber  regenerative  Neubildung  der  Lymphdrusen.  "\'^ircli.  Arch.,  120  Bd., 
1890. 

{       §  84.  Tlio  new=formation  of  the  red  blood-celLs  or  erythrocytes  oc- 

I  curs  through  the  mitotic  divisi(»ii  of  jiuclciitrd  young  forms  of  jcd  cells 
known  as  erythroblasts  (Bizzozero,  Xcumaiiu,  Flcmniiug).  In  the 
adult  this  uew-formation  is  restricted  to  the  bone-marrow,  and  this  is  true 


298 


THE    PROGRESSIVE  CHAXGEG. 


also  of  other  mammals,  birds,  reptiles,  and  tailless  amphibians,  while  in 
the  tailed  amphibians  and  in  fishes  the  spleen  also  takes  part  in  the  proc- 
ess. In  embryonic  life  the  new-formation  and  increase  of  the  red  blood- 
cell  takes  place  throughout  the  entire  vascular  system,  but  later  it  be- 
comes restricted  to  the  spleen,  liver,  and  bone-marrow,  and  finally  to 
the  last  alone. 

The  entrance  of  the  red  blood-cell  into  the  circulation  takes  place 
after  the  loss  of  its  nucleus. 

In  the  increased  new-formation  of  red  blood-cells  following  a  loss  of 
blood,  as  well  as  in  severe  chronic  anaemias  and  leukcemia,  nucleated  red 
blood-cells  may  appear  in  the  circulating  blood  outside  of  the  bone- 
marrow.  The  fatty  mari-ow  may  thereby  take  on  again  in  jjart  the 
character  of  the  splenoid  marrow,  this  change  being  accomplished  bj"  the  ! 
dilatation  and  congestion  of  the  blood-vessels  with  an  increase  in  the 
colorless  and  red  cells  of  the  marrow,  while  the  fat  j^resent  in  the  sup- 
porting reticulum  disappears. 

The  new=formation  of  the  colorless  cells  of  the  blood  and  lymph 
grouped  together  under  the  broad  teiin  leucocytes  occurs  essentially  iu 
the  lymphoid  tissue  of  the  lymph-glands,   mucous  membranes,  spleen, 
thymus,   and  bone-marrow;    but  leucocytes 
,,    _      ;^  within    the   blood-   and   lymph-vessels  andj 

.^1"  T^Sv"-^ — «        tissue-spaces   outside  of  these   organs   may, 

^y'.    :■.    ■:''"    ,*7'  t^  also  divide,  and  well-defined  foci  of  prolif-' 

'.    y  ..   ,  '  ^^~c        eration   may  thus  be  formed.       The  mouo- 

'^'"Y^'J.  :    '^,  '  ^  .  ■  nuclear  cells,  known  a.?,  Ii/mjihoci/tes,  develop; 

chiefly    in    the     first-named    regions,    and: 
numerous  karyomitoses  (Fig.  176)  are  con-; 
stantly    found    in    the    so-called    germinal! 
centres.       The  pohjmorplionudear  or  polynn-\ 
clear  leucocytes   and  the  eosinophile  cells,  on 
the  other  hand,  are  formed  in  the  bone-mar 
row.      Whether   the   large   cells   with  cleai 
nuclei  known  as  mononuclear  leucoc//fes,  an* 
the   transilion  forms   with    horseshoe-shapei 
nuclei  developing  from  the  latter,   are  als( 
formed    in    the    bone-marrow   is  doubtful 
They  can  also  be  regarded  as  more  fully 
developed  lymphocytes. 

A  pathological  increase  of  the  colorles. 
cells  (leucocythaemia)  may  take  place  through  an  increased  eniigratioi. 
of  cells  from  the  formative  tissues  without  an  actual  increase  in  cell 
production.  xV  long-continued  jiersisteuce  of  such  an  efflux  presuppose 
an  increased  pi-oduction  also. 

A  transitory  leucocythtemia  is  designated  leucocytosis,  while  a  perma 
nent  one  is  called  leulcemia.  The  former  is  characterized  by  an  increas 
ill  the  neutrophile  polynuclear  leucocytes,  rarely  by  increase  in  tli 
lymphocyles.  Two  forms  of  leukaemia  are  distinguished:  a  lympluvmi 
in  which  the  lym])hocytes  are  increased,  and  a  myehvmla  or  myeloid 
Imhivmia,  characteri/ed  by  the  appearance  in  the  blood  of  myelocytes,  momj 
nuclear  cells  with  neutr()i)hile  granulation  arising  in  the  bone-marro^^ 
(See  Pathology  of  the  Blood.) 

The  polynuclear  leucocytes  escaping  from  the  circidatory  system  she 
no  progressive  changes.     The  mononuclear  cells  of  the  blood  niay,  on  tl  , 
contrary,  appear  iu  various  forms  known  as  epithelioid  cells,  plasma-cell  < 


:'h 


Fig.  176.— Section  from  the  germi- 
nal f-etitre  of  a  mesenteric  gland  (after 
Flenimingi.  a.  Large,  t),  small 
IvniplMcytes:  <\  karyomitoses;  d.  di- 
re<'t  nuclear  division  or  nuclear  frag- 
mentation :  ('.  cells  containing  near 
the  nucleus  "tingible  bodies"  and 
small  yellow  pigment  granules,  whose 
'     'Icanceis  unknown,     x  400. 


XP:W-FOiniA'l'IOX    of    liLOOD-CKIJ.S.  299 

[•lasmatocj/tcs,  and  viast- cells.  With  reference  to  llicii'  power  to  give  rise 
;o  ditterent  forms  of  cells  they  may  be  desiuiiatcd  as  jiohihlasis  (JNIaxi- 
mow).    (See  also  chai^ter  on  the  Iiiliaiiiiiiator_\  >.'('\\ -loiiiial  ion  of  Tissue. ) 

Accordiiip;  io  Xcunmnn,  the  young;  forms  of  the  red  hlood-cclls  inuhiply  in  tiip 
ymphoid  marrow.  Hizzozero  and  Dcmjs  liold  that  tiiis  now- format  ion  takes  place 
lorinally  only  within  the  marrow-vessels,  and  the  new-formation  of  tlie  red  blood-cells 
s  completed  within  the  same.  The  change  of  the  nucleated  cells  into  non-uticleated  ones 
•s  brought  aixmt,  according  to  many  writers,  through  a  disappearance  of  the  nucleus. 
Vccording  to  Rindjleisch.  Howell,  Malassez,  and  Ma.rimoir,  the  nucleus  is  e.xtruded. 
According  to  Maxiniow,  there  maybe  distinguished  in  the  protoplasm  of  crythroblasts 
lossessing  old  pyknotic  nuclei  a  granular  area  surrounding  the  nucleus  an'd  a  homo- 
geneous peripheral  substance.  After  the  extrusion  of  the  nucleus  the  inner  granular 
'substance,  which  stains  witli  neutral  red  and  other  dyes,  is  at  first  preserved,  but  vanishes 
jn-ith  the  ripening  of  the  capsule. 

According  to  Bizzozcro,  the  young  forms  of  the  red  blood-cells  are  cells  of  an  individ- 
'aal  type  that  are  always  hiemoglobin-containing  and  have  no  colorless  ancestors.  Denys, 
^owit,  Howell,  and  Pappenheim,  on  the  contrary,  liold  that  they  arise  from  nucleated 
iuemoglobin-free.  colorless  cells  (basophile  leucocytes,  Pappenheliii)  believed  by  I)eni/s 
to  increase  within  the  marrow-vessels;  while  Li'iwh  thinks  that  the  colorless  antecedents 
if  the  red  cells,  which  divide  by  mitosis  and  which  he  calls  en/l/irohlasls,  occur  in  the 
liymph-glands  and  spleen  as  well  as  in  the  marrow,  and  lie  both  within  the  vessels  and 
I'in  the  meshes  of  the  reticular  tissue. 

'  Flcniming,  who  agrees  with  Bizzozero  concerning  the  haemoglobin-content  of  the 
nucleated  young  forms  of  red  cells,  is  inclined  to  assume  that  the  young  forms  present 
in  la'er  life  are  the  direct  descendants  of  the  young  forms  of  the  embryonic  period. 
Xeuniann  holds  that  this  hypothesis  is  not  sufficient  to  explain  all  the  phenomena  of 
later  life;  as,  for  example,  the  replacement  of  the  fatty  marrow  which  contains  no 
'nucleated  red  cells  by  blood-forming  lymphoid  marrow,  and  the  formation  of  ret!  blood- 
cells  in  such  newly-developed  marrow.  He  finds  himself  forced  to  the  conclusion  that 
,either  a  development  of  the  nucleated  red  cells  takes  place  from  the  leucocj^tes  of  the 
;l)lood  which  after  birth  are  carried  to  the  marrow  through  the  arteries,  or  that  they 
arise  from  the  tissue-elements  of  the  bone-marrow. 

'  Peirone  believes  that  the  red  blood-cells  of  the  mammals  are  only  apparently  non- 
jnucleated,  and  that  it  is  possible  by  means  of  especial  methods  of  fixation  and  staining 
ito  render  the  nucleus  visible.  This  invisible  nuclear  substance  is  iron-containing  and 
■shows  an  affinity  for  acid  stains,  while  the  nucleus  of  the  crythroblasts  stains  with  basic 
'dyes. 

Literature. 

{New-formation  of  Blood-cells. ) 

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Kiiochenmarkzellen.     Virch.  Arch.,  144  Bd..  1S96. 
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Arch.  ital.  de  Biol.,  xiv.,  1890. 
Blumenthal :   Rech.  sur  la  genese  des  cellules  sanguines,  Briixelles,  1904. 
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vi..    1891. 
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oiseaux.     lb.,  iv.,  1888. 
Dominici:   Origine  des  polynucleaires.     Arch,  de  mdd.  exp.,  1902. 
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iss:5. 
Flemming:    Zellvermehrung  in  Lvm|)lidnisen,  Theilungs:irten  <ler  Leukocvlen.     .\rch. 

f.  mikr.  Anat..  24  Bd.,  188.5;  Theihmgu.  Kernformen  bei  Leukoeyten.     lb,.  37  B.I.. 

1S91. 
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kernhaltiger  r.  Blutkorp.  in  kernlose.     V.  A.,  168  Bd.,  1902. 


300  THE    PROGRESSIVE    CHANGES. 

Israel  ii.  Pappenheim :  Entkernung  d.  Erythroblasten.     Virch.  Arch.,  143  Bd.,  1896. 

Jolly:    Diff.  types  de  glob,  blancs.     Lab.  d'hist.  du  Coll.  de  France,  1900. 

Levaditi:   Contrib.  a  I'etude  des  Mastzellen,  Paris,  1902. 

V.  Limbeck:    Klin.  Pathologic  des  Blutes,  Jena,  1896. 

Lowit:  Neubildung  ii.  Zerfall  weisser  Blutkorperchen.     Sitzber.  d.  K.  Akad.  d.  Wiss. 

in  Wien,  92  Bd.,  1885;    Anat.  Anz.,  i.,  1886;    Neubildung  u.  Beschaffenheit  d. 

weissen  Blutkorperchen.     Beitr.  v.  Ziegler,  x.,  1891;    Die  Anordnung  von  Leuko- 

blasten  u.  Erythroblasten  in  d.  Blutzellen  bildenden  Organen.     Anat.  Anz,,  vi., 

1891;   Arch.  f.  mikr.  Anat.,  38  Bd.,  1891. 
Malassez:  Gaz.  med.  de  Paris  1874  and  1878;   Arch,  de  phys.,  i.x.,  1882. 
Maurel:    Rech.  experimentales  .sur  les  leucocytes,  Paris,  1891. 
Maximow  :    Struktur  u.  Entkernung  d.  r.  Blutkorp.     A.  f.  Anat.,  1899. 
Mobius:    Zellvermehrung  in  der  Milz.     Arch.  f.  mikr.  .-inat.,  24  Bd..  1885. 
Mondino:    .Sulla  genesi  degli  elementi  del  sangue,  Palermo,  1888;  A.  ital.  deBioL.xii.,  i 

1889.  ' 

Mosso:   Umwandlung  d.  roten  Blutkorperchen  in  Leukocyten.   Virch.  Arch..  109  Bd., ! 

1887. 
Miiller:    Zur   Frage    der  Blutbildung.      Wien.  Sitzber.,   1889;     Zur    Leukamiefrage. 

Deut.  Arch.  f.  klin.  Med.,  48  Bd.,   1891;    Mitose  an  eosinophilen  Zellen.     Arch.  f. 

e.xp.  Path.,  29  Bd.,  1891. 
Negri:    Persistenz  des  Kernes  v.  Blutkorp.     Anat.  Anz.,  xvi.,  1899. 
Neumann:   Bed.  d.  Knochenmarks  fiir  die  Blutbildung.     Centralbl.  f.  d.  med.  Wiss., 

1868;   Arch.  d.  Heilk.,  x.,  1869;   Entwickelung  roter  Blutkorperchen  im  neugebild. 

Knochenmark.  V.  A.,  119  Bd.,  1890;  Blutbildung  b.  Froschen.  lb.,  143  Bd.,  1896. 
Oppel:    Die  Entstehung  der  rothen  u.  weissen  Blutkorperchen.     Cbl.  f.  allg.  Path., 

1892   (Lit.). 
Pappenheim:    Entwickelung  d.  Erythroblasten.     Virch.  Arch.,  145  Bd.,  1896  (LitV 

Entstehung  d.  roten  Blutzellen.     lb.,   151  Bd.,  1898;    Bez.  d.  farblosen  Blutkor- 
perchen zu  einander.     Virch.  Arch.,  160  Bd.,  1900. 
Paulsen:    Zellvermehrung  in  Lymphdriisen  u.  Tonsillen.     Arch.   f.  mikr.  Anat.,  24 

Bd.,  1885. 
Petrone:   Sur  le  sang.      Resume  des  travauxpubl.    A.  ital.  de  Biol.,  xxxvi.,  1901. 
Rindfleisch:   Knochenmark  u.  Blutbildung.    Arch.  f.  mikr.  Anat.  xvii.,  1879. 
Roemer:  Formativer  Reiz  der  Proteine  Buchner's  auf  Leukocyten.   Berl.  klin.  Wcch., 

1891. 
Sanfelice:   Genese  des  corp.  rouges  dans  la  moelle  des  os.      Arch.  ital.  de  Biol.,  xiii.. 

1890. 
Saxer:    Abstammung  d.  weissen  u.  rothen  Blutkorper  von  primiiren  Wanderzellen 

Cbl.  f.  allg.  Pathol.,  vii.,  1896. 
Schedel:   Zellvermehrung  in  der  Thymus.     Arch.  f.  mikr.  Anat.,  24  Bd..  1883. 
Schmidt:   Ueber  Blutzellenbildung  in  Leber  u.  M.    B.  v.  Ziegler,  xi.,  1892. 
Spuler:   Ueb.  d.  intracelluliire  Entstehung  roter  Blutkorper.     A.  f.  mikr.  Xn.,  40  Bd. . 

1S92.  1 

Timofejewsky:   Regenerat.  d.  r.  Blutkorperchen.     Cbl.  f.  allg.  Path.,  vi.,  1895.  I 

Trachetti:  Glob,  rossi  ed  emoglobina  nelle  anemie  sperim.     Arch,  per  le  So.  med.i] 

1896.  ! 

Zenoni:    Entstehung  versch.  Leukocytenformen.     Beitr.  v.  Ziegler,  xvi.,  1894,  \ 

i 
§  85.  The  new=formation  of  transversely  striated  muscle=fibreij 
takes  its  start  from  portions  of  old  muscle-tibres;  and  although,  afteij 
injury  to  a  muscle,  the  intermuscular  connective  tissue  may  be  excite(; 
to  active  proliferation,  there  is  formed  in  consequence  only  connective 
tissue,  or  probably  also  the  sarcolemma  of  new  fibres,  but  never  nevj 
contractile  substance. 

The  first  signs  of  a  formative  activity  of  the  muscle-fibres  after  injur;' 
appear  in  the  mu.scle-nuclei,  in  that  these  become  elongated  and  ther 
divide  into  a  varying  number  of  fragments.  Even  on  the  second  da;| 
there  may  occur  mitotic  division  (Fig.  177,  a,  h)  of  the  muscle  nucleilj 
This  form  of  division  seems  to  be  the  only  way  in  which  multiplicatioii 
takes  place,  and  under  favoraljle  conditions  it  occurs  very  actively  aftej 
the  second  day.  i 

The  beluivior  of  the  contractile  substance  of  the  muscle  differs  veri 
markedly  according  to  the  nature  and  extent  of  the  injury.     In  the  oasj 


REGENERATIOX    OF    MISCLK. 


301 


of  tnuimatic,  toxic,  and  aiuvniic  injuries  it  sulTers  a  frafjmentation  into 
larger  and  smaller  portions,  so  that  the  niusele-eells  eonie  to  lie  in  spaces 
of  varying-  size  between  the  detiitns  of  the  nuiscle-libres.  Crushing  and 
tearing  can  bring  about  a  wide  separation  of  llie  parts  of  the  contract iU', 
substance.  The  ends  of  the  i)ieces  of  juuscle  libres,  in  such  a  case,  iniiy 
be  conical,  obliciue,  transverse,  or  torn  in  an  iri-egnlar  edge,  but  not  iufic- 
cjuently  after  a  shoit  time  theends  become  split  into  two  or  nu)re  pointed 
lilaments  (Fig.  177  a). 

The  mitotic  division  of  the  muscle-nucleus  takes  j^lace,  not  only  in 
miclei  that  rest  upon  living  tibres  (a),  but  also  in  the  muscle-cells  lying 
free  in  the  spaces  between  the  separated  muscle-tibres  (/>) ;  and  in  bolli 
])laces  leads  to  tlu^  production  of  large  multinuclear  cells,  which  form 
nuiltinuclear  protoplasmic  masses  on  the  ends  of  the  muscle-tibres  (r,  f) 
as  well  as  on  the  body  of  the  fibres  (c).     Into  these  masses  the  trans- 


FiG.  177.— Portions  of  muscle-flbres  showing  regenerative  proliferatiim,  from  iniisrlc-wounds  of  dif- 
ferent ages  (FlemmiDg's,safranin).  a,  Pointed  ends  of  the  split  stunii)  of  a  mLis( 
sinn-Uj-'ures,  three  days  after  laceration  of  the  muscle;  Jb,  proliferated  musrle-iiiiclfi  tiaiisfiniiiiii  intu  (•••lis 
rich  in  prot4iplasm,  one  of  which  is  in  process  of  mitotic  division  ;  c,  piece  of  a  niuscle-llbre  eight  days  after 
tying  the  muscle;  d,  giant-cells,  enclosing  necrotic  pieces  of  muscle,  from  a  muscle-scar  twenty-six  days 
I'M;  e.f,  muscle-flbres  ending  in  protoplasmic  masses  (muscle-buds),  e,  from  a  muscle-scar  ten  days  old, 
/,  from  one  twenty-one  days  old ;  g,  dividing  muscle-flbres  from  a  muscle-scar  forty-three  days  old.    X  315. 


versely  striated  mu.scle-substance  passes  without  a  shaip  line  of  dcmarca- 
jtion.  There  occurs,  therefore,  at  the  same  time  icith  the  inxltipHciition  of 
]the  miclei  an  increase  of  the  sareojyJasni  of  the  muscle-fihrrs,  and  this  l>eeonies 
[distinctly  visible. 

'  The  muscle-cells  not  connected  with  living  contractile  substance  be- 
come changed  into  large  epithelioid  cells  icith  larf/e  nuclei  (/>).  Thi'ongh 
continued  division  of  the  nucleus  these  cells  become  transformed  into 
multinuchar  proto2)lasmic  masses  (d);  and  a  scar,  consisting  of  prolilcr- 
ating  connective  tissue,  of  from  eight  to  thirty  days  old,  contains  such 
giant-cells  which  often  enclose  the  renuiins  of  old  muscle-tibres  (d)  in 
,large  numbers. 

:  The  7iew  muscle-fibres  develop  for  the  chief  part  from  the  rirhti/  tinclr(drd 
mrcoplasm,  which  appears  in  the  continuity  an<l  at  the  ends  of  the  muscle- 
fihres,  in  connection  with  the  formation  of  numerous  large  nuch'i,  and 
which  through  its  increase  of  size  causes  an  increase  in  thetliickness  and 
length  of  the  muscles,  which  has  been  designated  budding  hy  Neumann. 


302  THE    PROGRESSIVE    CHANGES. 

\V'ith  the  transformatiou  of  the  sarcoplasm  iuto  muscle-fibrillte  there 
appears  gradually  a  longitudinal  and  later  a  transverse  striation,  a  sign, 
that  the  organic  structure  of  the  plasma  has  completed  its  development 
in  the  way  characteristic  of  muscle. 

The  greater  part  of  t\\Q  proUferating  muscle-cells  icMch  have  no  connection^ 
with  living  muscle-fibres  die ;  but  it  is  to  be  noted  that  they  persist  for  a; 
long  time^  so  that  not  infrequently  there  may  be  seen  in  muscle-scars' 
from  eight  to  forty  days  old  great  uimibers  of  protoplasmic  masses  very 
rich  in  nuclei.  Under  certain  circumstances  these  may  form  long,  con- 
nected bands,  or  rows  of  separate  pieces  of  protoplasm.  There  can  be' 
no  doubt  that  a  part  of  these  cells  under  favorable  conditions  become' 
transformed  into  transversely  stiiated  muscle-substance ;  and  this  takes' 
place  either  by  the  formation  of  new  independent  muscle-fibres  or  by: 
union  with  old  muscle-fibres  or  muscle-buds.  The  disconnected  new-' 
formation  of  muscle  from  proliferating  muscle-cells  occurs  particularly! 
when  the  contractile  subslauc;e  is  destroyed  while  the  sarcolemma  re-; 
mains  intact  (as  in  typhoid  fever).  On  the  other  hand,  the  formatiou' 
of  buds  is  observed  especially  at  the  ends  of  fibres  which  have  been! 
divided. 

The  buds  springing  from  the  ends  or  sides  of  muscle-fibres  may  cause! 
a  simple  elongation  of  the  muscle-fibre,  frequently  deviating  from  its' 
original  direction  (/).  Often  there  are  seen  fibres  which  ha^e  split  iutq 
two  or  three  jiarts  (ff),  so  that  the  old  fibres  branch  as  they  pass  into  thel 
muscle-scar.  As  far  as  we  know,  this  splitting  of  the  fibre  occurs  verji 
early  (a),  before  the  proliferating  muscle-nuclei  have  formed  much  sar-' 
coi^lasm,  so  that  the  proliferation  appears  first  in  the  split  portions  ol 
the  fibre.  As  a  result  of  such  splitting  a  muscle-scar  may  come  to  con  • 
tain  a  greater  number  of  muscle-fibres  than  were  originally  present  ii 
the  affected  area. 

llypcrtroplvj  of  transversely  striated  muscle  takes  place  through  ar 
enlaigement  of  the  individual  muscle-fibres;  the  thin  muscle-fibres  ii 
Ijarticular  becoming  increased  in  thickness  (Morpurgo).  The  nuclei  d( 
not  become  increased  in  number.  On  the  other  hand,  such  an  increas* 
does  take  place  in  the  case  of  a  growth  in  length  of  the  muscle;  and  i; 
the  result,  most  ])rol)al)ly,  of  amitotic  division  (Morpurgo).  ; 

A  ne\v=formatioii  of  heart=muscle  has  not  yet  been  positively  demon' 
strated.  After  injuries  of  the  heart,  division  figures  appear  in  the  mus' 
cle-cells,  but  after  a  few  days  these  can  no  longer  be  demonstrated,  an<i 
the  wound  heals  through  the  formation  of  ordinary  scar-tissue.  Focaj 
degeiiei'ations  of  the  myocardium  likewise  heal  by  connective-tissue  cica 
trization.  ^  ■ 

A  new=formatlon  of  smooth  muscle=fibres  as  well  as  regeneration 
occurs  alter  traumatic  or  toxic  and  ischtemic  degeneration.  It  occur 
also  in  hypertrophic  new-formations  of  muscle-tissue — for  example,  i . 
tumoi's — and  is  initiated  by  mitotic  division  of  the  nuclei  of  the  muscle^ 
cells,  which  is  followed  by  division  of  the  cells.  According  to  the  result 
of  expei'imental  work  and  also  of  observations  upon  the  muscle-tissues  o 
man,  the  reproduction  of  fibres  after  injuries  and  focal  degenerations  i, 
b\it  slight,  ceasing  after  a  short  period.  Thus,  for  examf>le,  defects  ii 
the  muscularis  of  the  stomach  and  intestines  or  of  the  bladder  are,  fo' 
the  chief  ]m\v{,  closed  only  l)y  connective  tissue. 

Hypertrophy  of  smooth  muscle=fibre  is  a  phenomenon  which,  withi. 
certain  limits,  is  of  very  frequent  occurrence.     In  the  pregnant  utem 


REGEXf:RATiox  OF  xp:rve-tissue.  303 

he  sizo  of  the  muscle-cells  may  leach  live  to  ten  times  Ih'e  ordinary  size. 
Jf  other  or«iaiis  the  bladder  most  frequently  shows  a  marked  hyi)ertro- 
phy  of  smooth  muscle. 

Literature. 

(Rcf/cneration  of  Striped  Musclf.) 

Barfiirth:  Zur  Kegcncratioii  (Ut  Gcwobc.     Arch.  f.  iiiikr.  Auat.,  I'.T  ]](i.,  1S91. 

Dore:   I)i'  la  n\i,^(.'iu  du  tissu  inuscul.,  etc.,  Paris,  1881. 

Felix:   Waclisthum  der  quergestr.  Musciilatur.     Zcitsclir.  f.  wiss.  Zool..  48  Rd.,  1889. 

Galeotti  u.  Levi:  Kegeu.  d.  quergestr.  Muskels.     Jkitr.  v.  Ziegler,  xiv.,  1898. 

V.  Kahlden:  Kcgen.  d.  quergestr.^Muskeln  (Referat).     Cbl.  f.  allg.  Path.,  iv.,  1803. 

Kirby:  I'utcrs.  lib.  Dc<;cucratiou  ii.  Kegeaeratiou  d.  Muskelgewebes      Bcitr.  v.  Zicg- 

l.r,  .\i.,  1892. 
Kolliker:  Gewcbelehro  des  Menschen,  1.,  1889. 

Kraske:  Uiiters.  iibcr  die  llegeueration  der  quergestr.  Muskelfasern,  Ilalle,  1879. 
Leven:    Rcgeucratiou  der  quergestr.  Muskelfaseru.     Deut.  Arch.  f.  klin.  Med.,  Ixiii., 

1S88. 
Morpurgo:  Ipertrofie  funzionali  dei  muscoli.     Arch,  per  le  So.  Med.,  xi.\.,  1895;  xxii., 

1898 ;   Yirch.   Arch.,   150    Bd.,   1897;    Kernwucherung    beim   Langenwachsthuin. 

Anat.  Auz.,  xvi.,  1899. 
Hauwerck:  Ueber  ^VTuskelregeneration  nach  Verletzungen,  Jena,  1890. 
Neumann:    Ueber  deu  Hcilungsprocess   uach   Muskelverletzungen.     Arch.   f.  luikr. 

Anat.,  1868. 
Panet:  Die  Entwickelung  der  quergestr.  Muskeln  aus  Sarkoblasten,  Wien.  1886. 
Robert:  Wiederbildung  quergestr.  Muskelfasern.     Beitr.  v.  Ziegler,  x.,  1891. 
Schaffer:  Ili'^tol.  u.  Histogenese  der  quergestr.  Muskelfasern,  Wien,  1893. 
Steudel  u.  Nauwerck:    Kegeueratiou  der  quergestr.  Musculatur.     Beitr.  v.  Ziegler, 

ii.,  1SS8. 
Valle:  liiueneraz.  dei  muscol.  volont.     Arch,  per  le  Sc.  Med.,  xxiv.,  1900. 
Volkmann:  Regeneration  des  quergestr.  Muskelgewebes.     Beitr.  v.  Ziegler,  xii.,  1893. 
Zaborowski:  Regen.  d.  quergestr.  Musk.     Arch.  f.  exp.  Path.,  xxv.,  1889. 
Zenker;  I  iber  die  Regen.  des  quergestr.  Muskelgewebes,  Leipzig,  1864. 

1  {^Regeneration,  of  Smooth  ]\fi(.sele,  and  of  Heart -m  t(. set e.) 

Askanazy,  S. :  Ueber  die  Regcueratior  glatter  Muskelfasern.     Inaug.-Diss.,  Kouigs- 

iiir.u-,  1891. 
Berent:  Heilung  von  Herzwunden.     Inaug.-Diss.,  Konigsberg,  1892. 
Bonome:  Heilung  von  Herzwunden.     Beitr.  v.  Ziegler,  v.,  1889. 
Busachi:    Ueber  die  Neubildung  von  glattem  Muskelgewebe.     Beitr.  v.  Ziegler,  iv., 

Goldenberg:  Hypertrophic  der  Herzmuskeln.     Virch.  Arch.,  103  Bd.,  1886. 
Herczel:  Muskelhypertrophie  bei  Darmstcnoseu.     Zeitschr.  f.  klin.  jMed.,  xi.,  188G. 
Jakimowitsch :  Regen.  glatter  3Iuskeln.     Cbl.  f.  d.  nied.  Wiss.,  Wien.  1879. 
Kolliker:  (ievvebelehre  des  Menschen,  i.,  1889. 
Martinotti:    Sugli  effetti  delle  ferite  del  cuore.     Giorn.  delhi  R.  Acead.  de  :\Ied.  di 

Toiiiio,  1880. 
Poggi:   La  cicatrisation  innnediate  des  blessures  de  restoniac.     J5eitr.  v.  Ziegler,  iii., 

1SS8. 

Ritschl:   Heilung  v.  Wundeu  d.  Magens,  Darmkanals  u.   Uterus.     Virch.  Arch.,  109 

r.l..  issT. 
Stilling  u.  Pfitzner:  Resren.  glatter  Muskeln.     Arch.  f.  mikr.  Anat.,  28  Bd.,  1886. 
TangI:   il.viMitn.phie  drs'llerzens.     Virch.  Arch.,  110  Bd.,  1889. 

S  80.    Regenerative  new=formation  of   the   nerve=elements  of  the 
central  nervous  system  through  the  nevv=formation  of  ganglion=cells 

most  ])r(>l)ahly  does  not  occur  in  man  and  mammals  in  post-emitryunal 
life.  Accordiuo;  to  the  iuvestis^ations  of  Stroebe,  on  the  other  hand, 
divided  nerve-fbrih  (in  mammals)  mat/  grow  length iri>.e  to  a  eertain  extent 


304 


THE    PROGRESSIVE  CHANGES. 


through  sproiduKj  of  the  axis-cylinder;  and  this  is  true  particularly  of  thfi 
fibres  of  the  i).\r:uiiidal  tracts  aud  tlie  posterior  roots,  both  of  wbicb 
after  being  divided  .grow  iuto  tlie  scar-tissue  developing  at  the  site  of  tb( 
wound,  tile  loinier  iu  a  downward  direction,  the  latter  upward,  A  com 
plete  restoration  of  nervous  tissue  does  uot  take  i)lace,  and  a  defect  ii 
the  spinal  cord  due  to  trauma  is  replaced  esseutiallj'  by  connective  tis 
sue,  in  part  also  by  neuroglia.  According  to  investigations  by  Borst, 
new  axis-cylinders  may  be  formed  within  the  new-formed  neuroglia  ir 
the  neighborhood  of  cerebral  lesions,  and  medullary  ner\'e-fibrils  maj'-be 
produced  by  the  outgrowth  of  old  fibres.  , 

Regenerative  and  hypertrophic  proliferations  of  neuroglia  are  pbe; 
nomena  which  occur  frequently  in  diseased  conditions  of  the  centra; 
nervous  system,  and  either  follow  degenerative  changes  of  the  nervoui 
elements,  or  iu  i)art  also  destruction  of  the   neuroglia,  or  they  mav 

appear  without  sucli 


antecedents,     in 


th.! 

ii; 


h 


Ij 


inult 
miTiicr 
with  li 


1<'M-|( 


-Sclt'iiitic  tissue  from  the  posterior  columns  of  a  rase  of 
I. IMS  (Miliums  tluid,  Mallorv's  method),  a,  Glia-cclN  with 
icMcsM's,  seen  in  longitudinal  section ;  L,  selerotic  tissue 
fsely  cut  glia  Hbres.     X  500. 


latter  case  arising 
pai't  during  the  i)erio(i 
of  development.         i 
The      new -forma, 
tiou  is  brought  abouj 
by  mitotic  division  oi 
the   nuclei    and  cellj 
bodies    of    the    gliaj 
cells,  eveutualh^  alsi 
of  the  ependyma-cell.'i 
The  newly  formej 
glia-cells     producj 
later  a  great  prof  usioi 
of     delicate    fibrillaj 
processes    (Fig.    17.j 
«),  and,  as  in  the  noi; 
mal  tissues  of  the  cei 
tral  nervous  systeiii 
there  may  be  distii: 
guished   among  tbesj 
cells  which  are  known  as  astrocytes  (Deiter's  cells)  two  varieties,  the  si 
called  '■^ mossy  cells"  (Kiir^strahler)  and  the  so-called '^6;/^/(/^/--ce?/6*"  (Lan* 
strahler)    with    long,    stiff,    less-freely    branching    jjrocesses    {a).      Tl 
processes  of  these  cells  form  sometimes  a  loose,  sometimes  a  dense  fel 
work  of  fine  fibrillse  {a,  h)  in  which  the  cells,  which  have  but  little  prot 
l)lasm,  are  embedded.     After  full  development  of  the  tissue  a  separatic 
of  the  processes  from  the  cell-bodies  may  take  place.     The  thickeuir 
of  tlie  tissue  caused  l)y  the  ])ioliferation  is  known  as  sclerosis. 

Regenerative  new=formation  of  the  nerve=fibres  of  the  periphen 
nervous  system  is  of  very  frequent  occurrence  and  takes  place  in  8 
those  cases  in  which  through  any  influence  the  continuity  of  a  nerv; 
fibre  is  entirely  or  partially  interrupted.  For  its  accomplishment,  bov 
ever,  it  is  indeed  necessary  that  the  ganglion-cells  whose  processes  for 
the  nerve-fibres  in  question  be  preserved. 

Wlien  a  nerve  has  been  severed,  the  axis-cylinders  and  medulla 
sheaths,  in  the  distal  i)ortion,  undergo  degeneration,  the  latter  breakii 
up  into  drop-like  detritus,  which  later  is  dissolved.  During  the  disi 
tegration  of  the  nerve-fibres  the  nuclei  situated  beneath  the  sheath 


KEGENKKATION'    of    XKin  KS. 


305 


Schwann  nndergo  mitotic  division  and  form  cells  rich  in  protoplasm, 

which  may  take  np  into  themselves  the  products  of  the  destruction  of 

the  nerve-libres. 

!      Of  the  proximal  portion  of  the  nerve  the 

])cripheral  extremity  alone  degenerates,  as 

tar  as  the  next  Ranvier's  node,  or  the  next 

one  beyond. 

The  regeneration  of  the  nerves  begins  a 

few  days  after  the  operation,  in  the  i)roximal 

portion,  about  0.4-2  cm.  above  the  cut  end. 

!      The  first  change  consists  in  a  swelling  of 

nidividual  axis-cylinders  in  the  jjeripheral 

|)arts  of  the  nerve-bnudle  of  the  proximal 

vnd,  which  is  later  followed  by  a  splitting- 

off  of  two  to  five  or  more  new  axis-cylinders. 

The  new  axis-cylinders  arising  in  this  way 

from  the  old  ones  grow  in   a   longitndinal 

ilirection  (Fig.   179,  «,  b)  and  form,  within 

the  sheath  of  Schv\-ann,  whole  bundles  (Figs. 

!l7}),  c;  180,  e)  of  newly  formed  nerve-fibres, 

which  for  the  most  part  fill  up  the  entire 

huiuMi  of  the   old   nerve-tubes,   and   indeed 

stretch  it,  and  more  rarely  enclose  remains 

pf  the  old  fibres  (Fig.  ISO,  /).     Single  filn-es 

linay  even  break  through  the  old  sheath  of 

Schwann,  and  then  either  extend  further  in 

the  endoneurium,  or  penetrate  through  the 

iperinenrium    of   the  nerve-bundle    into  the 

bpinenrium. 

I      In  this  way  there  are  formed  on  the  lower  end  of  the  proximal  i)orli(>n 

pf  the  nerve  a  large  number  of  new  nerve-fibres,  which  in  the  beginning 

consist  only  of  the  newly  formed  axis- 
cylindeis,  but  immediately  surround 
tliemselves  with  a  meduUaiy  sheath, 
which  by  reason  of  its  irregular  de- 
velopment gives  to  the  nerve-fibres  a 
varicose  appearance  (Fig.  17!),  r). 
Later  the  fibres  acquire  a  neurilemma- 
sheath  —  that  is,  a  connective-tissue 
covering  which  is  jirobably  formed 
from  the  nerve-corpuscles  concerned  in 
the  ]n()liferation. 

^^'hen  a  nerve  is  entirely  severed 
and  there  is  no  possibility  of  a  union 
with  the  distal  poi-tion — as,  for  ex- 
ample, occurs  in  all  ami)utations  of  the 
extremities — thei(^  is  formed  in  the  re- 
gion of  the  cuten<l  an  enibiyonic tissue, 
spi-inging  from  the;  connect i\-e  tissue  of 
the  nerves,  which  later  on  beconu's 
changed  into  connective  tissue.  In  the 
beginning  free  from  nerves  this  con- 
nective tissue  becomes  ])enet  rated  by 
young  nerves    growing   out   fiom  the 


Fig.  179.— Old  and  newly  formed 
nerve-flbres  from  an  amputation- 
stump,  in  lon^rituiiinal  section  (Miil- 
ler's  fluid.  WriireiCs  sluiu).  a,  /),  Old 
lUTVf-llliit's.  fi-diii  which  sc\ci-al  young 
ucfvc-lllitc^  h:i\c  L'lowii :  c.  iieuri- 
leimiia  Willi  VdUiitr  iiiTvc-lllircs.  X 
18(1. 


ndle 
(livid- 


Km.  180— On  - 

'f  the  median  nc]      ^ ... 

"'■''•'fi.nprv.Miiadu  four  muuilis  previously 

MiiM.Ts  iiuiil,  carmine),  a.  Perineurium: 
J.  ••n.ionfuriuMi;  c,  cros.s-section  of  a  vessel; 
'-  "  il  unchanjfed  nerve-Bbre;  e.  bundle  of 
ifw  ly  formed  nen'e-tlbres ;  f ,  newly  formed 
ifrves.  with  remains  of  old  fibres  Inside  the 
■ame  sheath,    x  200. 


.'0 


306 


THE    PROGRESSIVE    CHANGES. 


nerve-fibres  of  the  nerve-stump,  whicli,  arranged  in  small  bundles,  orj 
scattered,  grow  into  the  connective  tissue  and  penetrate  it  in  every  direc 
tion  (Fig.  181).     Not  infrequently  the  growth  of  nerves  is  so  extensive 
that  nodular  or  clubbed  swellings  (Fig,  181,  h)  arise  on  the  ends  of  the 
nerves.     Such  a  swelling  is  known  as  an  amputation -neuroma. 

When  a  nerve  after  division  is  again  united,  or  if  the  division  of  the- 
nerve  is  only  partial,  the  nerve-fibres  growing  out  from  the  proximal  eu(ij 

after  penetrating  the  connective  tissue! 
formed  in  the  site  of  the  wound,  may  ii' 
part,  or  all,  find  their  way  into  the  peri 
ipheral  portion  of  the  nerve  where,  in  th*' 
mean  time,  the  nerve-fibres  have  been  de' 
stroyed.  In  this  way  the  distal  end  viajj 
again  become  neurotized — that  is,  supplied 
by  new  nerves.  According  to  investiga, 
tions  of  Forssmann,  the  direction  of  th'' 
newly  growing  fibres  is  governed  Ir' 
chemotactic  influences  arising  from  th' 
disintegration-products  of  the  old  nerve 
fibres. 

According  to  the  investigations  cj 
Yanlair  the  growth  of  a  regeneratiu! 
nerve  is  about  0.2-1  mm.  daily,  accorc! 
ing  to  the  character  of  the  tissue.  ^ 
portion  of  the  new  nerve-fibres  may  pei; 
etrate  into  the  old,  empty  sheath  d 
Schwann ;  others  extend  into  the  epineu  | 
ium  and  perineurium,  and  in  this  situjj 
tion  grow  toward  the  periphery  to  til 
end-organ.  Single  fibres  may  pass  by  tlj 
end  of  the  nerves,  and  grow  toward  tlj 
periphery,  either  along  the  old  nerves  u 
by  an  independent  route.  Many  fibre 
which  leave  the  old  route,  are  finally  lo 
in  the  tissues.  In  the  lower  portion  j 
the  intermediate  substance  (Vanlair)  t]; 
nerve-strands  begin  to  collect  iui 
bundles  again,  and  with  the  formatif 
of  a  i)erineurium  about  the  latter,  the  r- 
generated  nerve  takes  on  more  and  mc; 
the  structure  of  a  normal  nerve.  \ 

The  above-described  process  of  reget 
eration  requires   for  its    accomplishmeli 
omi)lete  after  seve]l 


b 


Fir.  181.— Amputation-neuroma  of  tbe 
sciatic  nerve,  in  longitudinal  section  (am- 
putation of  nerve  nine  years  previously) 
(Miiller's  tluid).  a.  Nerve;  5,  neurouia. 
X  3. 


weeks   < 
montlis. 


even  months,    and  sometimes   is   not   complete  after  seveil 


The  question  of  tho  regeneration  of  the  central  nervous  system  is  still  un.T 
(liscnssion.  It  is  nciicrally  ,i(((]ii((l,  as  iiavinu'  1)t'('ii  cstiiblished  beyond  all  donbt,  t  t 
in  the  cold-bloddid  aiiiiuals,  n|itilcs,  and  tailed  aniplnbia,  a  regenerative  new-fori - 
.^ration  of  porliims  ot  the  ccnlral  nervous  system  can  take  place.  In  the  case  of  \va  ;- 
blixidcd  animals,  ]iail  iciilarl y  in  the  mammals,  the  majority  of  experimental  invc- 
i^alidiis  lia\e  failed  to  demimstrate  a  re,i:;('nerative  new-formation  of  gan,i;'lion-C( '• 
7'f 'Ave///,  \'i!:-iiii  and  others,  claim  to  iiave  ol)served,  after  injuries  of  various  kii  !, 
botli  a  new-formation  of  neuroglia  and  of  ganglion-cells  and  nerve-fibres;  but  e 
investigations  carried  out  in  my' laboratory  by  tscMstoicitsch  seem  to  me  to  contra<,;t 


REGENERATION     OF    N  Ein  K-TISSFE.  307 

these  assertions.  The  results  obtiiined  hy  G nine rt  in  expcriiiuntiil  work  with  pigeons 
I  agree  with  the  conchisions  arrived  at  hy  Tttrhifstoiritxch. 

I  Monti  and  Fiinclii  could  demonstrate  no  evidi-nees  ol'  ri'^fciieiatioii  in  the  ganglion- 

cells  of  the  sympathetic  after  injuries.  Tindli  found  only  degenerative  changes  ia 
I  the  ganglion-cells  of  tiic  iutervcrlctnal  ganglion  afl<'r  injury"of  the  same. 

The  new=fornnation  of  peripheral  nerve=fibres  lias"  been  made  very  frecim-nlly 
the  subject  of  experimental  research,  and  dillerenl  nliservers  have  come  tn  very  dill'er- 
eut  eoncl  isiiins  (see  Slr<>i/i, ,  /.  c.).  'i'liealiovedeserihed  mode  of  new-formation  I  regard 
I  as  tirmlv  established,  in  so  lar  as  its  essentials  are  concerned,  upon  tiii'  groinid  of  per- 
I  sonal  investigations.  1  have  been  unable  to  confirm  the  views  of  Soiiikiiui,  Dohlurt, 
I  Diii<zki(iru'z,  \'iitt,(i(i,  llV/r  MitrluH,  <;iiick,  BciwAc,  von  Biuifjiwr,  WutiiKj,  and  others, 
I  who  hold  that  the  new  fibres  in  the  distal  portion  of  the  severed  nerve  rise  aiitochthon- 
I  ously  fron\  the  nuclei  of  the  sheath  of  St'hwann,  or  from  the  old  axis-cylinder,  or  from 
I  a  protoplasmic  mass  formed  by  a  chemical  transformation  of  tiiu  meduilary  sheath  and 
I  axis-cylinders  {yeumitnn-Dohbevt).  The  view  held  by  Bethe,  that  tiic  uerve-;d)re3 
j  arise  without  participation  of  the  ganglion-cells  in  the  fused  ectodermatic  cells  wliose 
\  remains  later  represent  the  cells  of  Schwann,  appears  to  me  to  have  been  shown 
;  by  vou  KoUiker  to  be  incorrect.  Likewise,  the  attempt  made  by  J^'euinanii  and 
'  Wietuif/  {Marcliand)  to  bring  into  accord  the  established  fact  of  the  outgrowth  of  the 
I  axis-cylinders  of  the  proximal  portion  into  the  scar  muting  the  severed  ends,  witii  the 
I  theory  of  the  origin  of  new  nervetibres  from  the  nuclei  of  the  siieath  of  Schwami,  or 
I  from  the  remains  of  old  fibres,  or  from  both,  by  the  assumption  that  the  axis-ctylinders 
,  growing  from  the  proximal  end  convey  a  stimulus  from  the  nerve-centres  to  tlie  distal 
portion  and  thereby  make  possible  the  development  of  new  fibres,  1  regard  as  unsuc- 
'  ecssful,  and  hold  to  the  above-given  view.  lam  further  of  the  ojjinion  that  the  medul- 
lary sheath  is  not  formed  by  the  cells  of  the  sheath  of  Schwann,  but  represents  a  jiroduct 

■  of  the  axis  cylinders;  but  further  investigations  as  to  this  point  are  needed.  According 
I  \o  JSixi-l.  Mari/usco,  and  others  (see  Barbacci,  I.  c.)  there  occurs,  after  the  severing  of  a 
'  uerve.  first  a  degeneration  in  the  corresponding  ganglion-cells  with  disintegration  of 
i  the  Nissl's  bodies,  and  this  may  lead  to  the  ilestruction  of  individual  cells.  Later, 
I  progressive  changes  with  new-formation  of  chromatin   take  })lace,  and  may  lead  to 

■  hypertrophy  of  the  cells  {Marincxra);  these  changes  reach  their  maxinuun  in  about 
1  ninety  days,  after  wiiicli  time  theic  is  a  icturn  to  the  normal  condition. 

j  The  regenerative  new=forniatioti  of  the  tissues  of  the  eye  has  in  recent  yeais 
j  been  rei)eatedly  an  object  of  research.  According  to  Wolff,  Midler,  and  Koclm  the  liim 
i  of  tritous  may  regenerate,  after  removal,  by  means  of  a  proliferation  of  the  epithelium 

of  tlie  inner  layer  of  the  iris.     According  to  liothig,  the  same  thing  occurs  in  tiie  trout. 

Goniit  observed  in  rabbits,  after  the  lens  had  been  removed  in  such  a  manner  that  the 

capsule  and  some  of  the  equatorial  lenticular  fibres  and  cpitheliunr  of  the  anterior  wall 
i  were  left  behind,  that  there  occurred  a  proliferation  of  this  epithelium,  leading  to  the 
I  union  of  the  anterior  and  posterior  walls  through  cells  resend)ling  connective-tissue 
I  cells.  A  new-formation  of  lenticular  fibres  from  these  cells  does  not  take  place. 
j  Remains  of  the  lenticular  fibres  may  form  a  ru(limentar5^  useless  lens,  which  in  the 

ca.se  of  young  animals  may  become  somewhat  enlarged  through  the  growth  of  the  fibres. 
I  lidhdoiiih  obtained  somewhat  better  results  in  guinea-pigs.  In  the  human  eye  similar 
I  formations  are  seen  after  removal  of  the  lens,  and  are  known  under  the  name  of  "  Krys- 
j  talhvulst"  (B((a.s}.  According  to  Frctnke.  Ki-i'irkuudin,  and  Stoeirer,  the  sclera  possesses 
;  but  slight  power  of  proliferation.  Wounds  of  the  same  are  healed  chiefly  through 
.  proliferation  of  the  choroid  and  episcleral  ti.ssue. 

According  to  Baqitis,  there  occurs,  in  the  injured  retinrr  of  the  rabbit,  division  of 
!  both  ganglion  and  neuroepithelial  cells.  According  to  KriirkiiHuni,  the  pigment- 
j  epitiielium  is  capable  of  extensive  regeneration,  but  ueuroepithelium,  on  the  other 
J  band,  is  not  again  formed. 

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j  {Ilefjenendton  of  the  Elciiicitts  of  the  Cent  ml  Xrrroii.s  Si/.st/'in.) 

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308  THE    PROGRESSIVE    CHANGES. 

I 

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I 


TKANSPLAXTATIOX    AM)    IMPLANTATION.  309 

1882;  vi..  1885;  viii.,  1886;  Compt.  rend,  de  I'Acad.  des  sciences,  18Sr);  Sur  I'in- 
nervat.  indirecte  de  la  peau.  lb.,  188(5;  De  rorRanisat.  des  drains  de  Ciioutchouc, 
etc.  Revue  do  Chir..  ISSG;  La  suture  des  nerfs,  Bruxclles,  1SS<»;  La  persistance  de 
I'aptitude  reirenera trice  des  nerfs.  Bull,  ile  I'Acad.  Roy.  de  Beljri(iue,  1888;  Rech. 
chroiioinetriiiues  sur  la  regen.  des  nerfs.     Arch,  de  pliys..  vi.,  1894. 

dieting:   Regen.  periph.  Nerven.     Beitr.  v.  Ziegler,  xxiii',  1898. 

iVolberg:  Nervennaht.     Deut.  Zeitschr.  f.  Chir.,  xviii.  and  xix.,  1883. 

{Bcgeneraiion  of  the  Tissues  of  the  Ejic) 

•Baquis:  Etude  exper.  sur  les  retinites.     Beitr.  v.  Ziegler,  vi.,  1888. 

3arfvirth:   Reg.  d.  Auges  u.  d.  Linse  beim  Hidinerenihryo.     Verh.  d.  anat.  Cos.,  1902. 

;oluzzi:    Rigen.  parzialo  dell'  occhio  nei  tritoni.     Meni.  Ace,  Bologna,  i.,  1891, 

^ischel:    Regen.  d.  Linse.     Anat.  Anz.,  xiv.,  1898. 

jonin:   Regen.  du  cristallin.     Beitr.  v.  Ziegler,  xix.,  1890  (Lit.). 

Cochs:  Regen.  d.  Orgnne  bei  Amphibien.     Arch.  f.  niikr.  Anat.,  49  Bd.,  1897. 

Criickmann:   Pigmentzellen  dec  Retina.     Arch.  f.  Ophthalm.,  48  Bd.,  1899.  * 

tfiiller:  Regen.  der  Linse  bei  Tritonen.     Arch.  f.  niikr.  Anat.,  48  Bd.,  1896. 

landolph:    The  Regeneration  of  the  Crystallhie  Lens.     Johns  Hopkins  Hosp    Rep 

ix..  I'.tOO.  _  f        i-> 

>cliimkowitsch.:   Linsenregen.  bei  Amphibien.     Anat.  Anz.,  xxi.,  1902. 
Jtoewer:    Heilungsvorg.  bei  Wunden  d.  Aiiges.     Arch.  f.  Ophthalm.,  46  Bd.,  1899. 
:Volff:  Linsenregeneration  bei  Tritonen.     Biol.  Cbl.,  xiv.,  1896;  An.  Anz.,  xviii.,  ]9()(); 
\       Regen.  d.  Urodelenlinse.     A.  f.  Entwickelungsmech.,  xii.,  1901. 


II.  The  Results  of  Transplantation  and  Implantation  of  Tissues  and 
;  Organs. 

I  §  87.  The  local  regeneration  of  tissue  is,  as  mentioned  in  the  last  i)art, 
''ery  often  but  slight,  so  that  losses  of  tissue  may  be  followed  by  pcrma- 
jient  defects,  and  in  place  of  the  original  structures  there  may  appear 
jnly  a  cicatricial  tissue  of  a  lesser  value.  Consequently,  from  ])ractical 
leasous,  many  attempts  have  been  made,  through  transplantation  and 
mplantation  of  tissue,  to  aid  and  to  improve  the  liealing-i)rocess;  and 
uch  attempts  have  in  part  been  successful.  At  the  same  time  they  have 
Iso  thrown  light  upon  the  individual  life  of  the  tissues  and  ui)on  the 
jiehavior  of  the  organism  toward  imi)lanted  li\ing  tissue. 
I  The  most  successful  results  have  been  obtained  in  the  i runsjylfmtation 
f  tissues  u'kich  remain  connected  with  their  nutrient  vessels,  since  the  same, 
t  the  point  of  union  between  the  transplanted  portion  and  the  under- 
^'ing  tissues  upon  which  it  is  placed,  grow  together  with  the  latter  in 
ssentially  the  same  manner  as  do  the  edges  of  the  wound  in  the  case  of  a 
lit.  Tliis  method  is  utilized  most  fre<iuently  in  the  case  of  plastic  oi)er- 
jtions  upon  the  surface  of  the  body,  but  it  finds  a])plicati()n  also  in  inter- 
al  .surgery.  For  example,  wounds  of  the  bladder,  inteslim*,  ui-elers, 
iibes,  etc.,  may  be  easily  closed  througii  imi)lanlali(»n  of  the  omentum; 
nd  the  surface  presenting  upon  the  lumen  of  the  organ  concerned 
iecomes  Aery  quickly  covered  over  by  the  neighboring  epithelium,  which 
[xtends  over  it  from  the  edges,  or  is  also  transplanted  from  the  opposite 
jpithelial  suiface  (Cornil,  Carnot) ;  while  the  omentum  itself  gi-ows  to 
be  a<ljacent  wound -surfaces,  and  tluis  tlirough  changes  in  its  structure 
ompletely  closers  up  the  defect.  Very  often  sudi  an  implantation  of  the 
inentum  occurs  spontaneously,  as,  for  example,  in  the  case  of  tiiiuniatic 
|r  ulcerative  perforations  of  the  intestine,  stomach,  gMll-l)la(l(h'r,  etc., 
[nd  even  large  openings  may  be  closed  in  this  maiuici-.  As  experimental 
jivestigations  have  shown,  portions  of  intestine  i)ro\i(led  witii  blood- 
leSvSels  may  be  implanted  into  other  ])ortions  of  tlie  intestines,  into  the 
ladder  (Enderlc),  stomach  (Iteerink),  and  can  heal  perfectly  in  these 


310  THE    PROGRESSIVE    CHANGES. 

locations  M'ith  preservation  of  their  own  epithelinm.  Likewise,  portions 
of  bone  or  cartilaiie  connected  witli  the  periostenm  or  perichondrium 
respective!}',  and  with  nntrient  vessels,  may  be  imjjlanted  into  neighbor- 
ing tissne. 

Transplantations  of  tissues  completely  freed  from  their  basement= 
structures  have  also  been  snccessfnlly  performed,  since  cells  loosened 
from  their  connection  with  the  organism  are  able  to  preserve  their  vital- 
ity for  a  certain  length  of  time.  The  cells  of  the  epidermis  are  able  to 
live  for  the  longest  time;  when  kept  cool  they  may  be  preserved  alive 
for  several  (two  to  nine)  days  (Wentscher  claims  to  have  been  able  to' 
preserve  epithelium  alive  for  twenty-two  days).  Ciliated  epithelium  may 
also  be  preserved  alive  for  several  days  and  still  show  movements  of  the 
cilia,  Next  to  the  surface-epithelium  in  this  respect  stand  the  conuec-: 
five  tissues,  while  other  tissues  quickly  die,  the  cells  of  the  brain  autl 
kidney  most  rapidly,  dying  within  a  few  hours  after  an  obstruction  tci 
the  blood-supply.  According  to  the  investigations  which  have  beer 
made  up  to  the  present  time  the  tissues  of  the  skin,  periosteum,  inter 
articular  cartilages,  muscle  and  cartilage  easily  preserve  their  vitality 
for  two  to  three  days.  Morpurgo  found  cells  of  the  periosteum  to  b( 
capable  of  reproduction  even  after  seven  to  eight  days.  The  tissues  o . 
the  vessels,  tendons,  and  neurilemma  appear  to  be  somewhat  more  re 
sistant.  Exact  statements  with  regard  to  this  point  cannot  be  made  a 
present,  since,  on  the  one  hand,  the  expiration  of  life  does  not  take  plac'; 
suddenly,  but  gradually  with  the  constant  diminution  of  vital  cells;  andj 
on  the  other  hand,  the  conditions  under  which  the  excised  portions  o' 
tissne  aie  preserved  also  influence  the  duration  of  life. 

Ti-ampJantations  of  skin  give  the  best  results,  and  were  first  recon- 
mended  by  Keverdin  and  Thiersch  for  the  healing  over  of  broad,  opej 
wounds  and  have  since  been  extensively  used  for  this  purpose.  Thj 
material  used  consists  of  pieces  of  skin  which  may  be  taken  either  froji 
the  same  individual  or  from  another  person.  Ordinarily,  strips  of  ski! 
removed  by  means  of  a  sharp  knife  are  used,  which  include  the  tips  v 
the  papillai  and  the  uj)per  layers  of  the  corium.  Epithelium  in  conne^ 
tion  with  a  thicker  layer  of  the  corium  may  also  be  successfully  tranj 
planted,  and  in  the  case  of  injuries,  large  portions  of  the  skin  which  ha^j 
been  conipletely  torn  off  may  be  again  joined  by  healing  to  the  deep' 
tissues  on  the  very  same  spot  from  which  they  had  been  removed. 

The  transplantation  may  be  made  either  upon  a  fresh  wound-surf  a 
or  upon  one  already  showing  proliferation.  The  strips  of  skin  are  hej 
firmly  in  place  by  means  of  moist  bands  of  gauze.  The  pieces  of  ski 
become  fastened  to  the  surface  of  the  wound  by  means  of  coagulatj 
blood  or  lymph.  In  successful  cases  a  firm  union  with  the  underlyi ; 
tissne  takes  place  within  about  eight  days. 

The  nourishment  of  the  transplanted  pieces  (Fig,  182,  d)  is  obtaiujl 
first  from  the  tissue-fluids  which  exude  from  the  underlying  tissuj 
Later,  there  begins  in  the  latter  a  vascular  connective-tissue  proliferatiji  i 
(h,  c),  and  the  transplanted  portion  becomes  penetrated  fiom  below f  ! 
new  blood-vessels  (ff)  accompanied  by  fibroblasts,  so  that  it  finally  i- 
comes  interspersed  with  new  blood-containing  vessels  and  areas  of  grai  • 
lation  tissue.  Under  favorable  conditions  the  old  vessels  may  agjii 
become  opened  through  the  ingrowth  of  new  vessels,  | 

The  behaxior  of  the  transplanted  ]iortion  varies  in  individual  cas^,    j 
the  number  of  cells  living  and  proliferating  changing  with  the  cori- 


1 


TRAXSPLA  XT AT  ION. 


311 


ions.  Xpart  of  the  rr/^.s  of  the  tra)is2)la)ite(1  portion  Is  aJirat/s  Josf,  and  this 
s  shown  nuicroscopicjiUy  iu  part  by  tlie  repeated  (les<|uain:ition  of  the 
uiperlicial  laj^ers  of  tlie  epithelium  (/),  Other  cells,  Ixif/i  (■pi(h<rnil  <nid 
\'onnective-tissu€  cells,  proliferate  oikI  produce  new  tissue. 
I  The  linal  ouleome  of  a  suceessful  triuis])lanl;i1i()n  is  tlie  coverinj;-  over 
bf  the  area  with  trans})lanted  epithelium  and  in  i);irt  also  by  transplanted 
I'oriuni.  Through  the  hitter  it  is  made  ])ossible  that  the  cicatricial  aica 
I'omes  to  possess  papilla?.  To  what  extent  in  a  ,i;i\('n  case  the  snpeilicial 
ayers  of  the  cutis  aiise  from  the  skin-j;raft  or  to  what  extent  from  the 
issue  ui)on  which  it  is  planted,  cannot  be  determined      Jf  the  i)apillary 


Ajn^:!/ 


'^'^;;S^»^»i>wLJl 


Fig.  182.-Skin-ffnift  four  ;iTid  (inr-half  da 
"i  the  roriiiia;  h,  prdlirrnitinii-  L"aiii  lution-t 
iHirtion  (if  skin  ;  I.  ilcsiniamatidii  of  tlir  hornv 
Into  the  tninsiilaiiti-il  councctn  I- tissue.     ,v  H 


ilil  (foniialiu,  h;i'inato.Nvlin,  picrofiichsiiiK  ((.  Deep  laypr 
!!■;  r,  lioumlarv  of  pioliferatiiiK  zone;  d,  c,  transpUinted 
■r;  (/,  \asrularolTshoots  and  ^,'^lllullUion-tis^sue  extending 


bodies  remain  preserved,  a  jwrtion  of  the  ti.ssne  may  be  foiined  from 
! immigrating  fibroblasts.  After  a  time  the  transi)lanted  area  comes  to 
|C'ontain  nerves  which  grow  into  it  from  the  edges,  and  there  is  restored 
jtirst  the  tactile  sense  (Stransky),  later  the  sensibility  of  pain  and  temper- 
jature.  Xew  elastic  tissue  also  develops,  as  in  ordinary  scars,  from  the 
I  ends  of  the  old  fibres. 

I  Besides  skin-transplantations,  there  have  been  attempted  transplanta- 
(tionsof  almost  all  the  tissues:  periosteum,  bone-marrow,  bone,  muscle, 

nerves,  thyroid,  pancreas,  adrenals,  mammaiy  gland,  mucons  glands, 
I  ovary,  testis,  etc.;  also  of  tissue-combinations,  as,  for  <'xani])le,  a  rat's 
!  tail  from  which  the  skin  has  been  strii)ped.     Kmlnyonal  tissue  has  also 


312  THE    PROGRESSIVE    CHANGES. 

been  transplanted  in  a  variety  of  Mays.  Finally  the  attempt  has  also 
been  made  to  transplant  tissnes  from  one  animal  to  another  of  a  different 
species. 

Such  transplantations  have  been  made  npon  open  vronnds,  into  the! 
subcutaneous  tissues,  peritoneal  cavitj',  glandular  organs  and  lungs, 
either  by  direct  operative  procedures  or  by  the  introduction  of  the  tissue 
into  the  blood-stream  through  the  blood-vessels. 

The  results  of  all  these  experiments  may  be  summed  up  as  follows: 

In  all  transplanted  tissues  there  oecurs  first  a  degeneration,  and  a  part  of 
the  tissue  dies.  After  a  certain  time  there  usually  results  ix,  proliferation'. 
of  the  remaining  portion,  which  may  lead  to  a  new-formation  of  tissue.; 
Connective-tissue  cells  form  new  connective  tissue ;  periosteum  and  end 
osteum  form  bone  or  connective  tissue ;  muscle-cells,  new  muscle ;  carti 
lage,  new  cartilage;  surface  epithelium,  new  ei^ithelium  (epithelial  cysts). 
Of  the  glands  the  thyroid,  mucous  glands,  and  mammary  glands  maj: 
form  new  glandular  tissue,  while  such  a  new-formation  does  not  tak(; 
place  in  the  case  of  the  kidney,  liver,  testis,  and  ovary.  In  the  case  o: 
the  liver  only  the  epithelium  of  the  bile-ducts  proliferates.  Only  in  th«' 
case  of  the  transplantation  of  the  ovary  into  the  peritoneal  cavity  of  tb' 
same  animal  can  the  ova  ripen  and  pregnancy  occur  (Knauer,  Eibbert- 
Gregorieff).  The  tissues  of  young  individuals  in  general  show  a  greate,' 
capacity  for  proliferation  than  those  of  old  ones.  In  the  case  of  th(i 
transplantation  of  complicated  tissues,  as,  for  example,  the  skinned  tai: 
of  a  rat,  all  the  different  tissues  may  produce  new  tissues  and  the  whol 
piece  groAv. 

Enihryonal  tissue  can  likewise  grow  after  transj)lantation  and  becoin| 
differentiated,  and  it  is  shown  that  firm  cartilage  in  particular,  which  i:' 
later  life  shows  but  little  power  of  proliferation,  is  longer  preserved  an<i 
shows  further  growth,  while  the  delicate  soft  tissue-formations  easily  diei 

After  a  certain  time  there  occurs  In  almost  all  the  transplanted  tissues! 
as  well  as  in  the  newly  formed  tissue,  a  retrograde  change,  and  they  ai! 
finally  destroyed  through  the  ingrowth  of  tissue  from  the  neighborhood.  Thj 
time  at  which  this  occurs  varies  with  different  tissues,  and  is  dependei' 
partly  upon  the  character  of  the  tissue,  and  partly  upon  the  surroundiuj 
conditions.  Implanted  surface -epithelium  can  under  certain  conditioij 
remain  permanently,  and  give  rise  to  epithelial  cysts.  Portions  of  thyroic 
mammary  gland,  and  pancreas  are  xjreserved  for  a  long  time.  Cristiai! 
found  pieces  of  thyroid  intact  two  years  after  implantation.  The  majoJ 
ity  of  the  tissues,  however,  disappear  within  a  few  months.  In  glanc' 
which  are  not  capable  of  proliferation  the  gland-cells  die  first.  If  all  < 
the  implanted  piece  is  not  destroyed  it  may  become  encapsulated. 

Tissue  of  difi'erent  species,  when  transiDlanted,  does  not  grow,  but 
either  destroyed  or  encapsulated,  sometimes  C[uickly,  sometimes  slowly. 

According  to  the  published  observations,  the  implantation  of  tissue  do 
not  lead  to  the  formation  of  a  permanent  tissue  from  the  transplanted  pie<, 
except  in  tlie  case  of  the  transplantation  of  skin.  Nevertheless,  such  £ 
implantation  may,  under  especial  conditions,  have  a  transitory  orpermii 
nent  value.  The  implantation  of  thyroid  or  pancreas  tissue  may  for 
c^irtain  time  dieck  the  harmful  consequences  of  the  loss  of  these  gland 
Through  implantation  of  a  tissue  into  a  defect  a  temporary  filling  of  tl 
latter  may  be  produced,  and  the  neighboring  tissues  are  thus  permitted 
proliferate  for  a  longer  time,  and  to  form  a  greater  amount  of  new  tissv 
along  the  framework  afforded  by  the  implanted  portion,  and  so  finally 
close  up  the  defect  completely.  "^  Bone  (not  connected  with  nutrient  ve 
sels)  when  implanted  into  a  portion  of  the  skeleton  is  destroyed,  ai. 


TRAXSPLAXTATIOX    AND    l.MPLAN  lATION.  .{lo 

absoibod  (equally  so  in  either  case,  whether  liviiij:;  bone  or  (lead  and 
macerated  boue  is  implanted),  and  is  replaced  by  new  bone  arisiii<;-  t'loin 
the  neighborin.u-  periosteum  and  endosteum.  Tn  this  May  there  may 
be  obtained  a  better  healing-  of  the  bone-defect,  and  such  imi)lantations 
,of  biuie  or  car(ila,i;e  may  also  be  made  use  of  in  the  case  of  otiier  tissues, 
for  the  stimulation  of  a  moie  abundant  production  of  tissue  for  the  pur- 
pose of  lillinii,-  up  tissue-defects. 

The  transi)lantationof  nerves  has  never  resulted  in  the  new-format  ion 
of  a  nerve  from  the  transplanted  i:»iece.  The  attraction  which  the  prod- 
ucts of  disintegration  of  a  nerve  (Forssmann)  exert  upon  the  axis-cylin- 
ders growing  into  the  wound  may  be  utilized  to  direct  the  course  of  the 
growing  nerves  into  certain  channels. 

Literature. 

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wii..  1895. 
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Ut.  xii.,  189-2. 
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314  THE    PROGRESSIVE    CHANGES. 

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4  7  Bd.,  1»98. 
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Kiuwickhingsmech.,  vi.,  1898. 
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Marchand:   Knochcntransplantatiou.     Verh.  d.  Deut.  path.  Ges.,  ii.,  Bedin,  1900. 
V.  Mang-oldt:  Ueberhautung  vou  Wunden  durch  Epithelaussaat.     Dent.  med.  Woch., 

iSli.");  Einptiauz.  v.  Rippenknorpelin  Kehlkopf.    Langenbeck's  Arcli.,  50  Bd.,  1899. 
Minkowski:  Unters.  uber  Diabetes  mellitus.     Arch.  f.  exp.  Path.,  31  Bd.,  1893. 
Morpurgo:  Vita  propria  d.  Periostzelleu.     Virch.  Arch.,  157  Bd.,  1899. 
Mosse:  La  grefife  osseuse  heteroplast.     Arch,  de  phys.,  viii.,  1896. 
Neumann:  ]S'ierentransplantatiou.     Arch.  f.  Entwickehmgsmechan.,  vi.,  1898. 
OUivier:  Traite  exper.  et  clin.  de  la  regenerat.  des  os,  1867;   De  la  greffe  osseuse  ehez 

riionniie.     Arch,  de  pliys.,  1889. 
Plessing:  Ihuitvcrptianzimg  nacn  Tliierscli.     Langenbeck's  Arch.,  37  Bd.,  1888. 
Raehlmann:    Anheiluug   transplant.   Lippenschleiuihaut.      Beitr.  v.  Ziegler,  xxvi., 

is;»!t. 
Reerink:  Experimente  iiber  Transplantationeu  am  Mageu.     Beitr.  v.  Ziegler,  xxviii., 

190.1. 
Reverdin:   De  la  greffe   epidermiqne,  Paris,  1872   (u.    Gaz.    des  hop.,  1870,  1871); 

Transpl.  de  peau  de  grenouille  sur  des  plaies  humaines.     Arch,  de  med.  exp.,  iv., 

1S92. 
Ribbert:    Das  patholog.  Wachsthum  d.  Gewebe,  Bonn,  1896;    Veriind.    transplant. 

Gcwebe.     Arch.  f.  Entwickelungsmech.,   vi. ;   Transplant,    v.    Ovarium,    Hoden, 

Mamma.     lb.,  vii.,  1898;  Exp.  Erzeugung  von  Epithel-  u.  Dermoidcysten.    Deut. 

Z.it.  i.  Chir.,  47  Bd.,  1898. 
RutkoviTski:  Harnblasenplastik.     Cbl.  f.  Chir.,  1899. 

Saltykow:  Transpl.  zusammenges.  Theile.     Arch.  f.  Entwickelungsmech.,  ix.,  1900. 
Scheff:  Die  Keplantatiou  der  Zii'hne,  Wien,  1890. 

Schloflfer:  Osteoplastik  bei  Defecteu  d.  Tibia.     Beitr.  v.  Bruns,  xxv.,  1899. 
Schultz:  Transpl.  v.  Ovarien  auf  miinnl.  Thiere.     Cbl.  f.  allgem.  Path.,  xi.,  1900. 
Schweninger :  Ueber  Transplant,  u.  Implant,  v.  Haaren,  Miiuchen,  1875. 
Stilling:  Entwickl.  transplant.  Gewebsteile.     Verh.  d.  D.  path.  Ges..  vi.,  1904. 
Stransky  :  Seusibilitat  transpl.  Hautstiicke.     Wien.  med.  Woch.,  1899. 
Sultan:  Transpl.  v.  Schilddrusen.     Cbl.  f.  allgem.  Path.,  1898. 
Tietze  :  Netzplastik.     Beitr.  v.  Bruns,  xxv.,  1899. 

Traina  :  Transplant,  v.  embryon.  Gew.  ins  Ovarium.     C.  f.  a.  P.,  xiii.,  1902. 
Valan :  SuH' innesto  dell' osso  sul  cranio.     Arch,  per  le  Sc.  Md.,  xxii.,  1898;  Arch. 

it.  de  Biol.,  xxxi. 
Vanzetti  :  Transplant,  della  tiroide  embryonale.    A.  per  le  Sc.  Med.,  1903. 
Weiss:  Transplant,  v.  Bindehaut  auf  Hornhaut.     Arch.  f.  Augeuh.,  33  Bd.,  1896. 
Wentscher  :  Eigenleben  menschl.  Epidermiszellen.     Beitr.  v.  Ziegler,  xxiv.,  1898. 
Wetzel:  Transplantationsversuche  mit  Hydra.     Arch.  f.  mikr.  Anat.,  lii.,  1897. 
Zahn  :  Sur  le  sort  des  tissus  implantes  dans  I'orgauisme.     Congres  med.   Internal,   de   ' 

Geneve,  1876;  Schicksal  in  den  Organismus  implant.  Gewebe.     Virch.    Arch.,  95 

Bd.,  1884. 

IV.  Metaplasia. 

§  SS.  Tissue  metaplasia  is  that  process  by  which  a  tissue  already  \ 
fonnrd  is  r/Hiiu/cd  into  aiiollter  closely  related  without  the  intervention  of  I 
a  cellular  embryonic  or  granulation-tissue  stage.  Tissue  metaplasias  ! 
l)lay  a  very  important  role  in  the  development  of  the  individual  connec- 
tive-tissue foi-mations,  paiticuiarly  in  the  formation  of  bone,  cartilage,  ' 
an<l  marrow-tissue.  Through  proliferation  of  the  periosteum  or  endos-  ' 
teum  there  is  often  first  produced  ordinary  fibrillated  connective  tissue  ; 
which  later  undergoes  a  transformation  into  osteoid  tissue,  bone,  or  carti-  ' 
lage.  In  the  case  of  a  mrtaplasia  of  connective  tissue  into  osteoid  tissue  there 
occurs  Mithont  fnilhcr  cell -])rol iteration  a  condensation  of  the  ground- 


METAPLASIA. 


315 


^lll)stilllce  (Fig.  183,  a,  h)  which  loads  by  ii  gi-adual  transfonnation  (o 
iIh'  fonnation  of  an  osseous  giouiKl-siibstance  (r)  staining  r<'<l  witli  cai-- 
iiiiiie  or  eosin  or  fuchsin.  Shonhl  Ihcrc  lurUn'r  occur  a  deposit  of  liinc- 
>alts  (Fig.  184,  r)  true  boni/  irnhccuhv  may  be  fornicd. 

In  tile  nietaphisia  of  connective  tissue  into  cartiltige  tln^  gioiind  sub- 


I 


'^^:^^i^. 


Tu;  is>  -  Pi  iu)^t(  al  foi Illation  of  bout  lu.ii.i-.  < 
toxyliii.  puiic  acid,  iuclism  )  a,  FihullaU'd  count  iti 
condensation;  c,  fully  developed  bone.     X  300. 


( i.i^fatic  (ai<  luoiihi  of  <i 
tihsUf,    h,  tonnecti\e  ti'-- 


stance  becomes  thicker  but  at  tlie  same  time  more  clear  and  stains  less 
intensely  (Fig.  185,  e)  than  the  connective  tissue  (&).  The  cells  in- 
ciease  in  size  and  come  to  lie  in  round  spaces.  Such  changes  may  be  ob- 
MTved  in  the  jieriosteuni  and  endosteum  as  the  result  of  traumatic  oi- 
infectious  iDrocesses  or  in  the  new-formation  of  fibrous  tissue  associated 
with  tumor  formations  (Figs.  183  and  185").  In  the  healing  of  wounds 
iu  the  tracheal  cartilages  which  are  first  closed  by  scar-tissue  developing 
from  the  perichondrium,  cartilage  may  be  developed  later  in  the  same 
manner  (Fig.  18G,  ft). 

If  normal  or  jiathological  urtr-fonncd  cartilage  hrcomes  pcnctrafcd  hi/ 
hh,o(l-rr.ssr]s  the  cartilage- eel  Is  after 
ilie  dissolving  of  the  ground-sub- 
--tance  may  form  reticular  coiniective 
ii.s.si(c  through,  the  development  of 
liianched  processes  (Fig.  187,  b,  c), 
wiiich  through  the  enclosure  of 
iiKirrow-cclls  takes  on  the  chai-aeter 
nf  iiiarroic-tls.sue,  or  through  the  tak- 
ing up  of  fat  by  the  cells  nniy  be- 
come changed  into  adipose  tlt^-sKe.     If 

!  iu  the  vascularization  of  the  caiti- 

'  lage  trabeculfB  of  cartilage  remain, 
these  may  be  transformed  into  ofiteoid 
tissue  (Fig.  188,  /)  ^vhich  Avhen 
stained  with  lieematoxylin  and  eosin 


Fig.  184.— Formation  of  bono  from  cnniK'ctive 
tissue  (alcohol.  hiEmatoxylin).  Cross-section 
throuffh  a  bone  trabeculaln  iirocess  of  formation; 
from  an  ossifying  tlbronia  of  ttic  iHTinstciim  of 
the  iiii|»'i'  Jii"'.  '(,  (diincctive  lissiir  ;  /^  tliick- 
encd  tissue,' foniiinfi  tln'  jmiuiidwdik  nf  llicnew 
liiiuc;  r,  deposits  of  limc-salls;  ./,  coiiucclive-tls- 
siie  cells;  (h,  bone-cells.     X  isd. 


316 


THE    PROGRESSIVE    CHANGES, 


takes  an  iuteuse  red  staiu,  while  the  uuchauged  cartilage  stains  blue. 
Through  the  deposit  of  lime  salts  it  may  later  be  changed  into  bone. 
In  chronic  inflammation  of  the  joints,  caiiilaf/e  may  be  transformed  %  ' 


PiQ  185  — Periosteal  formation  of  cartilage  in  metastatic  carcinoma  of  a  rib.  (Hsema-t 
toxylin,  picric  acid,  fuchsin.)  a,  Fibrillated  connective  tissue;  b,  connective  tissue  undergoinjj 
condensation;  c,  fully  developed  cartilage.     X  300. 


Fig  186  —Healed  tra(  hcotomy  wound  in  llic  ciicoul  cartilage,  fiftv-two  days  old  (Formal 
hffimatoxynn,  and  eosin.)  a,  UKi  cartiugi ;  0,  0,  conneciive  ussue  arising  from  the  periuhondrii 
undergoing  metaplasia  into  cartilage.     X  60. 


METAPLASIA. 


317 

lace  is 


ordinarij  fihrilJated  connective  li.ssiic,  part  iciilaily  wIumi  its   litM 
covered  with  couuective  tissue. 

The  metaphistic  processes  thus  described  aie  comieclcd  m  ilh  preced 


i:^^ 


Fig.  187.— Metaplasia  of  lartilaL't'  into  rciiculai'  tissue,  in  arthritis  fungosa  (alcohol,  hcDinatoxylin). 
a.  Hyaline  cartilage ;  b,  tissue  consisting  of  branctied  cells ;  c,  cartilage-cells,  set  free  by  the  litiuefaction  of 
the  basement-substance  of  the  cartilage,  and  becoming  transformed  into  cells  of  mucous  tissue.    X  400. 


»|* 


^■ 


:^w^}:'\^»ws>^  ^•^W'W\%w.'Si 


■  :i}^ 
m 


m^/ 


I  f^'G;  188.— Metaplasia  of  cartilage  into  osteoid  tissue,  in  a  callus  fourteen  days  old  (Milller's  fluid, 
I P'*"™ acid, ha?matoxylin,  carmine),  a.  Hyaline  cartilage;  7»,  marrow-spaces;  c,  blood-vessel;  d,  cellular, 
*^f  ti  '*'""''"^  niarrow;  f,  osteoid  tissue;  g,  osteoblasts;  /t,  cartilage-cells  freed  through  the  disappearance 
orthegnmnd-substance;  i,  proliferating  cartilage-cells  in  opened  capsule ;  /c,  proliferating  cartilage-cells 
I  m  closed  capsule.    X  200. 


inj;  proliferations  and  may  be  associated  tint  licr  a\  itli  a]>])earances  of  pro- 
liferation. But  there  occur  metaplasias,  such  as  arc  described  above, 
which  have  no  connection  with  any  prolifciat  i\ c  clianjxc,  or  are  only  as- 


318  THE    PROGRESSIVE    CHAXGES. 

sociatc'd  with  it  at  a  later  i^eriod;  thus  myxomatous  tissue  may  become 
chaugediiito  adipose  tissue  if  the  star-shaped  tissue-cells  become  changed 
iuto  round  fat -cells  through  the  taking  up  of  fat,  while  the  mucoid  ground- 
substance  disappears.  Lymphadenoid  tissue  may,  after  the  disappear- 
ance of  the  lyuii)hoid  elements,  be  changed  into  adipose  tissue  through 
the  taking  up  of  fat  into  the  cells  of  the  stroma.  Through  the  disap- 
pearance of  fat,  adipose  tissue  may  take  on  the  appearance  of  mucoid 
tissue,  and  occasioually  comes  to  coutaiu  mucin. 

lu  the  change  of  connective  tissue  into  myxomatous  tissue  the  fibrillfe 
vanish  and  there  appears  in  their  place  a  jelly-like  mucus.  If  numerous 
lymphoid  round  cells  collect  in  fibrillated  connective  tissue  and  there  oc- 
curs at  the  same  time  a  reticulation  or  a  disappearance  of  the  connective- 
tissue  fibres,  while  the  connective-tissue  cells  remain  preserved  and 
through  the  formatiou  of  processes  unite  themselves  to  form  a  reticular ; 
tissue,  lymphadenoid  tissue  may  be  developed.  i 

Epithelial  metaplasia  occurs  most  frequently  in  chronic  inflamed ' 
mucous  membranes,  for  example,  uterus,  urethra  (gonorrhoea),  nose  i 
(oziena),  and  the  trachea,  cylindrical  epithelium  being  transformed  intoi 
pavement  epithelium. 

This  change  occurs  in  the  following  manner :  after  repeated  loss  of 
the  original  epithelium  the  regenerating  epithelium  changes  its  character. : 
In  mucous  membranes  possessing  stratified  pavement-epithelium  the 
upper  cell  layers  may  show  cornification,  not  only  in  places  which  nor-; 
mally  possess  pavement-epithelium,  as,  for  example,  the  tongue  audi 
cheeks,  but  also  in  those  possessing  transitional  epithelium  (the  uriuaryj 
tract),  or  cylindrical  epithelium  (nose,  ureters,  and  gall-bladder).  lu 
connection  with  this  phenomenon  should  be  mentioned  the  fact  thati 
epithelial  tumors  arising  in  mucous  membranes  possessing  transitiona 
or  cylindrical  epithelium  may  bear  the  character  of  squamous-cellet' 
epithelial  tumors. 

Literature. 

{^[ef  aplasia.) 

Dietz  :  riatteuepitlielkrebs  d.  Gallenblase.     Y.  A.,164Bd.,  1901. 
ringer:  Die  clironische  Uretbralblennorrhoe.     Arcb.  f.  Derm.,  Erganzungsbeft,  189l' 
Hansemann  :  Studien  ilb.  Specificitat,  Altruismus  u.  Anaplasied.'Zelleu,  Berlin,  189^,,. 
Hildebrandt :  Ueber    eineu    Katarrh    d.    weibl.    Gescblecbtsorgaue.       Samml.   klii};- 

V(.rtr.,  No    32. 
Kanthack  :  Stud.  lib.  d.  Histologie  d.  Larynxschleimliaut.     Yirch.  Arch.,  119  and  I'-i 

]'»\..  1800.  "  I 

Kischensky  :  Plattencpithelkrebs  der  Nierenkelche.     B.  v.  Ziegler,  xxxi.,  1901.        i 
Lubarsch  :  Die  Metaplasiefrage.    Arb.  a.  d.  p.  I.  v.  Lubarsch,  Wiesb.,  1901. 
Neelsen  :  Ilistol.  Veriind.  1.  d.  chroa.  eutziindet.  Urethra.     Vierteliahrsschr.  f.  Dern' 

ISST.^  i 

Ohloff :  Epithelmetaplasie  u.  Kre])sbildiuig  in  Gallonblase  ii.   Trachea.    Inaug.-Dis^j 

(Jrcilswald,  1891. 
Pollack:  Bcitr.  z.  Metaplasiefrage.     A.  a.  d.  p.  I.  v.  Luharscli,  Wiesb.,  1901.         ' 
Sangalli  :  Die  Metaplasie  d.  krankh.  Gcwebe.     Int.  r,(itr.,  Festschr.   i.    Virchow,  ii 

r.<;rlin,   1891.  I 

Schmiedeberg  :  Die  chemi.schc  Zusammensetzung  des  Knorpels.     Arch,  f .  exp,  Patji 

IS'.il. 

Schiichardt :  Ueber  d.  Wesen  d.  Ozacna.    Saniinl.  klin.  Vortr.,  No.  340,  Leipzig.  ISl! 
Virchow  Gesannnelte  Abbandl.,  Frankfurt,  1856,  pp.   500,   509;  Celiularpathol., 

.\utl.,  ]).  70.     Virch.  Arcii.,  Sand  97  Bd.,   Deut.  nied.  Woch.,  1884. 
Zeller  :  Plattenepithel  im  Uterus.     Zeitschr.  f.  Geburlsh.,  xi.,  1885. 


CHAPTER  yil. 
Inflammation. 

I.  The  Early  Stages  of  Acute  Inflammation. 

§  89.  Uuder  the  desiguatiou  inflammation  aio  i;r(>iiiH'(l  tliosc  ])a(lio- 
I  logical  i^henoniena  which  represent  a  combination  of  different  patholog- 
ical processes,  coiisiGting;  on  the  one  hand  of  tissue=degenerations  and 
tissue=proliferations,  and  on  the  other  of  pathological  exudations  from 
.the  blood=vesseIs.  Degenerations  of  tissue  and  patholoyieal  exudations  init- 
iate tltc  proeess ;  with  these  tissue-proliferation  is  sooner  or  later  assoeiaied, 
the  latter  leading  in  the  further  course  of  the  process  to  a  eotnpnisatioa 
for  the  disttirbanee — that  is,  to  healing.  The  proliferation  of  tissiif  may, 
therefore,  be  regarded  n^  regenerative,  but  such  new-formation  of  tissue 
may  be  iu  excess  of  that  which  is  useful  to  the  body.  The  tissnc-dcgen- 
I  orations  and  proliferative  j^rocesses  described  in  the  previous  chapters 
I  appear  for  the  greater  part  as  participating  factors  in  inllammation  ;  the 
I  proeess  aequiring  its  inflammatory  charaeter  through  the  eombination  of  tissue- 
\  degenerations  and  tissue-ptroliferations  with  pathological  exudations. 
j  Deeper  tissue-lesions — that  is,  injury  of  tissues  containing  blood-vessels — ■ 
'which  in  some  way  or  other  affect  the  vascular  systiMu,  wdl,  thenfore, 
,  constantly  bear  at  S(»ne  time  during  their  course  the  character  of  a)i  inflamma- 
tion. The  formation  of  scar  tissue,  the  healing  of  transplanted  tissues,  as 
;  briefly  described  in  the  last  chapter,  ahvays  take  place  through  processes 
\  essentially  inflammatory  in  nature. 

1  Exudation  in  acute  inflammation  is  constantly  associated  with  a 
t pronounced  hypera^mia,  which  api»ears  even  befoie  the  beginning  of  the 
i exudation,  and  hence  ushers  in  the  latter.  As  a  residt  of  the  combina- 
;tionof  hypertemia  and  exudation  the  inflamed  tissue  becomes  reihUMied 
land  swollen.  When  situated  on  the  surface  of  the  b(»dy,  where  a  cooling 
of  the  tissues  takes  i)lace,  the  increased  flow  of  warm  blood  from  the 
deeper  tissues  causes  a  local  increase  of  tempei-ature.  If  thetissne  af- 
jfected  contains  sensory  nerves,  the  sensation  of  pain  will  be  pr<iihiced  as 
the  result  of  the  changed  conditions  in  the  inflamed  aica. 

Redness,  swelling,  increased  warmth,  and  painfulness  of  the  in- 
flamed tissue  are  i»lienonuMui  which  e\'en  in  ancient  times  Mcie  regaided 
by  i»liysicians  as  the  signs  of  inflammation  ;  and  rubor,  tumor,  calor,  and 
dolor  weie  designated  by  (V-Isus,  at  the  beginning  of  our  er:i,  as  tlie 
cardinal  symptoms  of  inflammation.  To  these  toui-  was  then  added 
still  a  further  symptom,  functio  Iresa,  altered  function  of  tiie  inflamed 
tissue. 

The  causes  of  inflammation  may  lie  either  in  mechanical,  thermal, 
electrical,  or  chemical  influences,  as  well  as  in  the  influence  of  parasites. 
The  connnon  characteristic  of  all  these  injurious  agencies  is  the  produc- 
tion, in  the  first  place,  of  a  local  tissue-degeneration,  which,  when  of  a  certain 
extent  and  intensity,  is  associated  with  disturbances  of  the  circulation  and  of 
the  vasadar  secretion.     The  causes  of  inflammation  aie  not  speciflc;  any 

3ia 


820  INFLAMMATION.  m 

injurious  agent  may  excite  inflammation  if  on  tlie  one  hand  its  action  is 
sufficiently  intense  to  cause  certain  disturbances  of  circulation  in  asso- 
ciation with  tissue-degenerations,  but  on  the  other  hand  not  so  intense  as 
completely  to  destroy  the  tissue  and  stoj)  the  circulation. 

The  great  majority  of  the  causes  of  inflammation  reach  the  human 
organism  from  the  outside,  but  excitants  of  inflammation  may  be  formed 
also  within  the  body.  In  the  first  place  bacteria  which  have  j)enetrated  i 
into  the  tissues  very  often  form  within  their  protoplasm  or  from  sub-  | 
stances  present  in  the  body  certain  products  which  are  capable  of  excit- 
ing inflammation.  Moreover,  substances  that  excite  inflammation  may 
arise  within  the  organism  without  the  aid  of  parasites ;  particularly  as 
the  result  of  the  death  of  large  masses  of  tissue  from  any  cause,  as,  for 
example,  as  the  result  of  anaemia,  or  when  as  the  result  of  disturbances 
of  metabolic  processes  (gout)  products  of  metabolism  are  deposited  in 
the  tissues. 

The  causes  of  inflammation  may  act  upon  the  tissues  either  from  the 
portions  of  the  body  accessible  from  without,  or  from  the  lymph  and  the 
blood;  and  we  may,  therefore,  distinguish  ectogenous,  lymphogenous, 
and  haematogenous  inflammations.     Through  the  spread  of  an  inflam- 
mation to  neighboring  tissues   there  arises  an  inflammation    by  con- 
tinuity ;  as  the  result  of  the  transportation  through  the  lymph  or  blood  ; 
stream  of  an  agent  causing  inflammation,  there  are  produced  metastatic  i 
inflammations.     If  injurious   substances   are  discharged  through  the! 
excretory  organs,  excretory  inflammations  may  arise. 

When  a  local  injury  to  tissues  has  reached  such  a  degree  as  to  pro-j 
duce  the  exudation  characteristic  of  an  inflammation,  there  is  usually] 
found  in  the  first  place  a  congestive  hyperaemia,  as  a  result  of  which] 
the  blood  flows  through  the  dilated  blood-channels  with  increased  veloc- 
ity. After  a  short  time  there  is  a  lessening  of  the  speed  of  the  circula-j 
tiou  which  leads  finally  to  an  abnormal  slowing  of  the  bIood=current. 

The  first  disturbances  of  circulation,  which  find  expression  in  the 
congestive  hyperaemia,  may  be  due  either  to  a  stimulation  or  paralj 
of  the  vasomotor  system  or  to  a  direct  action  upon  the  A'essel -walls,  p'ar-i 
ticularly  upon  the  arterial  walls,  leading  to  a  dilatation  of  the  lumen. 
Although  these  disturbances  very  frequently  precede  the  iuflammatorji 
exudation,  they  do  not  form  an  essential  characteristic  of  inflammation, 
and  occur  very  often  without  being  followed  by  an  inflammatory  exuda* 
tion.     Further,  they  may  be  absent  during  the  course  of  an  inflammation 
The  circulatory  disturbances  characteristic  of  inflammation  are  showi 
only  when   the   slowing  of   the   biOod=current   and    the  pathological 
exudation  from  the  blood=vessels  set  in.     The  slowing  of  the  blood' 
stream  in  the  dilated  channels  and  the  pathological  exudation  are  del 
pendent  upon  a  change  in  structure,  art  alteration  of  the  vascular  wallsl 
through  which  there  results  a  lasting  dilatation  of  the  vessel  and  a 
adhesion  of  the  blood  to  the  vessel -wall,  causing  an  increase  of  frkiiou 
resistance  and  an  increased  permeaJyility  of  the  vessel- wall.     In  the  capi  ■ 
laries  the  persistent  dilatation  is  in  great  part  the  result  of  relaxation  of  tl- 
connective  tissue  surrounding  the  capitlarieS)  inasiiiiicO  as  the  thinness  of  tl) 
capillary  walls  makes  this  tissue  bear  the  greater  part  of  the  blood-pres; 
ure  resting  upon  them. 

The  tissue=iesion  which  leads  to  the  phenomena  of  inflammatory  di 
turbances  of  cii-culation  and  exudation  usually  afi'ects  all  parts  of  tl 
tissue,  but  under  certain  conditions  may  be  limited  to  the  vessel-wal 
particularly  in  the  case  of  a  ha?matogenous  inflammation,  in  which  tl 


THE    EARLY    STAGES    OF    ACl  TE    1  M  LAM  M  A'l'K  ).\.  :V2\ 

njmious  agent  acts  from  the  blood.  However,  the  tissue  in  the  reji:ion 
iidjoiiiiiij;'  the  capiUaiy  walls  must  soon  become  involved  in  association, 
[nie  tissue-chanjics  brouiiht  about  by  the  excitants  of  intlammation  aie 
soinetimes  only  sliii;ht,  and  even  on  microsc'o[)ical  examination  are  eithei" 
lot  recoi;iiizable  at  all  or  only  witli  dilliculty;  at  other  times  tiu'y  are 
iu)re  se\ere,  so  that  they  may  be  easily  icco^uized  e\-en  on  macr<»st'oi)ic. 
''xamination.  The  latter  is  particularly  the  case  uiicn  sonu;  time  has 
•lai>s«'d  after  the  action  of  the  injurious  a,n-ent.  Durinj^  tlie  further 
•ourse  of  the  inllammatory  process  there  are  often  added  to  the  lesions 
iproduced  directly  by  the  causes  of  iidlammation  other  tissue-chan<i;es, 
which  are  brought  abont  by  the  inllanimat(My  disturbances  of  circulation 
jiiul  the  collection  of  exndate  in  the  tissues. 

If  in  any  tissue  the  cause  of  inllaminalion  has  led  to  that  alteration 
,>f  t lie  v«'ss('ls  which  is  the  recpiisitc^  anteceikMit  of  an  inllammatory  dis- 
turbance of  the  secretion  of  the  vessels,  i.e.,  the  formation  of  an  intlam- 
iiiiatory  exudate,  and  if  as  a  result  of  this  there  is  already  evident  a 
t^lowing  of  the  blood-stream,  the  capillary  circulation  becomes  irregular, 
!;ukI  there  occurs  here  and  there  either  stagnation  or  a  peimanent  or 
It ransitory  stasis.  Since  in  this  event  the  white  blood-coii>uscles  often 
{lemain  clinging  to  the  Aessel-walls  while  the  red  blood-cells  are  carried 
nil,  there  arises  in  the  capillaries  a  more  or  less  maiked  increase  of 
\vhite  blood=corpuscles  as  comi)ared  to  the  red.  In  the  veins,  in  which 
tliei-e  can  l)e  distinguisheil  in  tlie  normal  circulation  an  axial  red  stream 
;iinl  a  peripheral  i)iasma-zoiie  free  ti'om  cells,  a-  greater  or  less  iiUmber  of 
leucocytes  pass  over  into  the  peripheral  plasma=zone,  when  tlui  slow- 
jiiig  of  the  circulation  has  reached  a  certain  degree.  A  still  greater  slow- 
jing  of  tlui  current  leads  to  the  passing  over  of  blood-plates  and  red 
[l)lood-cells  into  the  peripheral  plasma-zone,  and  finally  the  difference 
Ihetween  the  axial-stream  and  the  peripheral  zone  maybe  entirely  lost. 
I  Wlien  leucocytes  pass  over  into  the  peripheral  zone  they  either  roll 
Ijiloiig  in  the  same  or  cling  to  the  wall  of  the  vein,  either  to  roll  on  again 
latter  a  time  or  to  remain  permanently  attached.  If  this  oeeurrence  leads 
jto  a  marked  accumulation  of  leucocytes  along  the  vein-walls,  the  eondi- 
'tioii  is  known  as  the  marginal  disposition  of  the  white  corpuscles  (Fig. 
189,  (/). 

Following  the  accumulation  of  the  leucocytes  in  the  cai)illaries  and 
tlie  marginal  disposition  in  the  veins  there  occurs  later  an  cmif/ration  of 
\flw  Iriirori/fe.s  (Fig.  189,  (1,  e)  from  the  vessels  involved,  and  at  the  same 
itinie  a  ])iniriiif/-<nif  offiiidfroiii  flw  rr.s.srJs  into  ilio  tissues. 
\  The  emigration  of  the  white  corpuscles  is  an  active  process,  wliich 
lis  accomplished  through  the  aimeboid  mo\ement  of  the  cells,  and  to  a 
certain  extent  occurs  under  normal  coiidil  ions.  The  cause  of  tlu^  mark«'d 
(emigration  seen  in  inflammations  is  <l(»iil)tless  a  change  in  the  vessel- 
Kvalls,  which  favors  the  clinging  of  the  cells  to  the  walls  and  tln'ir  i)as- 
Isage  through  the  latter.  According  to  investigations  by  Arnold,  Thoiiia, 
'and  others,  the  leucocytes  pass  out  through  the  lines  of  cement-substance 
[lietween  the  endothelial  cells;  and  inthe  alteration  of  the  vessel-wall  «lue 
to  inflammation  localized  defects  occiii-  in  the  wall  as  the  result  of  the 
widening  of  tliese  lines.  The  emigration  is  accoini)lished  1>y  tlie  leuco- 
cytes first  sending  a  process  through  the  vessel-wall,  tlu^  reinaiiidei-  of 
the  cell-l)ody  then  flowing  after  the  i)rocess,  until  finally  tlic^  entin^  cell- 
body  is  outside  of  the  vessel.  Arrived  lier(^  the  leucocytes  first  remain 
lying  in  the  immediate  neighborhood  of  the  point  of  diapedesis,  but 
■'»f ten  wander  farther,  the  direction  of  the  wandering  being  determined 
21 


322 


INFLAMMATION. 


partly  bj^  mechanical  siimuU,  partly  by  chemotaxis — that  is,  the  repelling 
or  attraetiug  iutluences  exerted  by  chemical  substances  present  in  solu- 
tion in  the  tissue- juices.  Possibly  chemotactic  influences  sometimes 
exert  an  action  even  upon  the  leucocytes  in  the  capillaries  or  those  ic 
the  peripheral  zone  of  the  veins.  The  cells  emigrating  from  the  vessel; 
are  at  tirst  polynuclear  leucocytes,  but  lympliocytes  may  very  soon  ac. 
company  them.  The  polynuclear  cells  which  occasionally  alone  past^ 
out,  and  in  great  numbers,  are  after  their  emigration  known  as  pus- 
cells. 

The  pouring=out  of  the  fluid  exudate,  whose  composition  always, 
differs  more  or  less  from  that  of  the  normal  tissue-lymph,  and  which  is. 
characterized  by  a  relatively  high  albumin-content,  is  a  process  which  i; 


Fig.  189. —Inflamed  human  mesentery   (osmic-acid  preparation),     a.  Normal  trabecula;  h,  noni' 
epithelium  (endothelium);  c,  small  artery ;   d,  vein  with  leucocytes  arranged  peripherally;   e,  white  bloc 
cells,  which  have  emigrated  or  are  emigrating ;  /,  desquamating  endothelium;  /,,  multinuclear  cells; 
extravasated  red  blood-cells.    X  180. 

also  to  be  referred  to  an  alteration  of  the  vessel-wall,  in  consequence  \ 
which  the  secretory  f  miction  of  the  latter  suffers  a  disturbance.  It  taki 
place  at  the  same  time  with  the  emigration  of  the  leucocytes,  but  mi« 
begin  before  this  event,  and  may  occur  also  in  cases  in  which  the  emigr' 
tion  of  the  leucocytes  (for  example,  as  a  result  of  a  paralysis  of  the  sauij) 
does  not  take  place  at  all,  or  remains  within  very  narrow  limits.  T.i 
composition  of  ^/^e  ea;it(Zate  is  dependent,  in  all  cases,  partly  upon  the  '■ 
pecial  property  of  the  affected  vessels,  which  always  varies  according;') 
the  tissue-formation  to  which  the  "sessels  belong,  and  partly  upon  tfe 
degree  of  vascular  alteration ;  and  it  may  be  assumed  that  the  album  |- 
content  is  the  higher  the  greater  the  damage  to  the  vessel- walls.  If  te 
extravasated  fluid  contains  fibrinogenic  substances  and  fibrin-ferme  , 
coagulation— that  is,  a  separation  of  fibrin— takes  place. 

If  tlie  alteration  of  the  vessels  is  of  a  very  high  degree,  or  if  at  i.e 
sanu;  time  there  is  a  marked  stasis,  red  blood-cells  may  also  pass  ct 
of  the  vessels  (Fig.  189,  y)  along  with  the  fluid,  either  by  rhexis  or  dr 


INFLAMMATORY    EXIDATIOX.  323 

pedesis.  According  to  Thonia  and  Engelmann  the  diajMMlosis  occurs 
l)articnilarly  in  those  places  M'here  leucocytes  liaNc  i)reviously  i)assed 
thnuiiih  the  vessel-wall,  and  the  escape  of  icd  l>h)«>d-eells  may  lV)lh)\v 
very  ([uickly  by  the  same  route.  Since  the  red  blood-cells  are  not  mo- 
tile, their  escape  must  be  regarded  as  a  passi\e  process  performed  under 
the  intluence  of  the  ])ressure  within  the  capiUaries. 

The  escape  of  blood-plates  into  the  exudate  may  take  place  both  in 
exudates  rich  in  cells  and  those  containing  but  few,  but  occurs  particu- 
larlv  in  exudates  characterized  by  a  rich  content  iu  fibriu  and  red  blood- 
cells. 

Tissue=proliferation— that  is,  the  division  of  cells  and  nuclei — is  first 
recognizable  about  eight  hours  after  the  action  of  the  injurious  agent ; 
and  in  many  cases  appears  much  later.  There  are  i)iesent,  therefore,  in 
ease  the  intlammatiou  does  not  arise  iu  a  tissue  already  in  a  state  of  pro- 
liferation, the  characteristic  appearances  of  inflammatory  exudati(»n,  and 
with  it  also  the  tissue-degeneration,  long  before  the  proliferation  begins. 

The  clinical  significance  of  the  term  inflammation  {inflammaiio,  phh>;/».sis)  lias 
[Changed  but  little  in  the  course  of  time,  since  the  cardinal  symptoms  of  inllammatiou 
set  forth  by  Celsus,  and  accepted  by  Galen,  are  recognized  as  such  at  the  i)resent  day. 
Nevertheless,  the  views  regarding  the  different iatioa  of  the  essential  from  the  unessential 
in  the  symptom-complex  of  intlanunation  and  the  accurate  determination  of  the  true 
nature  of  the  process  have  differed  greatly.  A  comparison  of  the  expressions  concerning 
these  points  made  hy  the  more  modern  writers  {Virchow,  von  Jii'ckUn;///au.sen,  Cohnheim, 
l\>nfich\  Samuel,  Thoma,  yeumann,  Strieker,  Ileitzmann,  Grairitz,  J,etier,  Mtturttnikoff, 
and  others)  shows  that  no  single  writer  defines  infiammatioa  in  the  sanu;  waj'  as  any 
iitlier,  or  interprets  in  exactly  the  same  way  any  one  of  the  individual  phenomena  of 
inflammation.  Ponflck  designates  as  the  cause  of  infiammation  the  disturbance  of  e(jui- 
lil>rinni  in  the  tissues,  "but  hesitates  to  designate  retrogressive  changes  as  an  indis- 
pi'ns;ible  attribute  of  the  infiammatory  process,  and  doubts  wholly  tliat  they  should  be 
r.-irarded  as  the  point  of  departure  and  the  chief  feature  of  the  process."  I  am  of  the 
ipinion  that  "a  disturbance  of  the  tissue-equilibrium"  is  nothing  more  than  a  degener- 
iiive  change  of  tissue,  and  regard  Ponflck's  statement,  though  directed  against  my  defi- 
nition, as  harmonizing  with  my  views.  Moreover,  I  once  again  emphasize  the  fact 
that  the  alteration  of  the  vessels  is  a  necessary  requisite  for  exudation,  and  that  this 
alteration  is  nothing  else  than  a  tissue-degeneration. 

'  It  was  formerly  believed  that  hyperaunia  was  the  essential  symptom  of  inllamma- 
!;ion.  Rokitansky  held  that  every  inflammation  was  characterized  by  a  dilatation  of  the 
bapillaries,  slowing  of  the  blood-.stream,  and  bj'  stasis,  which  was  caused  bv  a  thicken- 
ing of  the  blood  through  the  effusion  of  serum  and  the  adhesion  of  the  red  blood-cells 
:<>  one  another.  Iknle,  Stillinf/,  and  liokiianskij  attributed  the  dilatation  of  the  vessels 
md  the  slowing  of  the  circulation  to  a  paralysis  of  the  nerves  of  the  vessels,  the  cause 
|>f  which,  according  to  llenle  and  Rokitansky,  is  an  increased  stimulation  of  the  sensory 
inerves;  while  according  to  Stilling,  the  cause  lies  in  a  paralysis  of  the  nerves  due  to 
Hie  inflammatory  irritant.  Eisenmann,  Heine,  and  Bviicke,  sought  to  attribute  the  cir- 
rulatory  disturbances  to  a  primary  spasm  of  the  vessels  brought  a])out  by  the  irritation 
f'f  sensory  nerves,  which  produces  behind  the  contracted  portions  of  the  vessels  a  slow- 
ing of  the  current,  irregular  circulation,  and  finally  also  stasis.  V<>;iel,  Eintmrt,  I'af/it, 
uid  others,  on  the  other  hand,  attriliuted  tlu;  dilatation  of  the  vessels  and  the  stasis  to 
'in  abnormal  attraction  of  the  blood  l)v  the  tissues.  Against  these  views  it  must  be 
iiiaintained  that  all  the  distm-bances  of  circulation  produced  by  contraction  or  dilatation 
!)f  the  vessels,  indeed,  introduce  or  accompany  the  infiammatory  disturbances  of  circu- 
Jation,  i.e.,  those  heading  to  exudation,  and  may  exert  a  modifying  intluence  upon  the 
■^ourse  of  the  infianunation,  but  do  not  form  an  essential  part  of  the  jirocess,  and  may 
lie  entirely  wanting,  or  may  appear  without  the  accompaniment  of  an  inflammatory 
(?.xudatc. 

S  Rokitansky  sought  to  explain  the  pouring  out  of  fluid  from  the  vessels  in  inflamma- 
ion  by  the  assumption  that  with  the  dilatation  of  the  vessels  the  walls  of  tiie  latter  be- 
ame  tiiinned  and  more  permeable.  ]'of/rl,  G.  Emmert,  and  Paget,  on  the  other  hand, 
nade  this  phenomenon  also  dependent  upon  an  increased  attraction  between  the  blood 
lind  the  tissue  parenchyma  or  juices.  Viichoir,  however  (1854),  believed  that  part  of  the 
)X'idate,  and  indeed  that  which  collected  in  the  tissue-spaces  and  is  poured  out  upon 
M  free  surfaces  of  the  body,  to  be  the  result  of  mechanical  pressure  in  the  vessels,  i.e.. 


324  INFLAMMATION. 

pressed-out  blood-serum;  while  a  part,  which  is  chiefly  taken  up  by  the  "irritated", 
cells,  is  to  be  regarded  as  a  product  of  an  increased  drawing  of  the  blood-element: 
through  the  tissues,  as  a  kind  of  nutritive  educt.  Of  the  cells  collecting  in  the  iu 
flamed  area,  he  believed  that  all  originate  from  a  proliferation  of  the  tissue-cells  oc 
curring  as  the  result  of  the  action  of  the  inflammatory  irritant. 

The  recognition  that  the  formation  of  the  exudate  is  to  be  referred  to  an  injury  o 
the  vessel-walls  Ave  owe  chiefly  to  Colinlieirn,  whose  investigations  along  various  line^ 
were  completed  by  ^S(umlcl,  Arnold,  Thoma,  Binz,  and  others.  Cohnheivi  also  showe(' 
that  in  inflammation  the  colorless  corpuscles  emigrate,  and  form  an  essential  constitueii 
of  the  inflammatory  exudate. 

J9«</w/«'i!  C' l^^cli.  anatomiques  et  phjrsiologiques  sur  la  structure  interne  des  ;ui 
maux  et  des  vegetaux  et  sur  leur  motilite,"  Paris,  1842,  p.  214)  and  Midler  {r//il<m>],/ 
Magas.,  xxix.,  1846,  pp.  271,  398)  had  as  early  as  the  years  184'3  and  184G  already  d( 
scribed  the  escape  of  colorless  corpuscles  from  the  blood-vessels.  These  observatioi 
had,  however,  fallen  completely  into  oblivion  until  Cohnlieim,  in  1867,  rediscovered  tli 
phenomenon. 

According  to  researches  of  f<clilhtrfirK];ii  {l^ar/cr's  Arch.,  Bd.  i.),  the  peripheral  di; 
position  of  tlie  Icueoeylcs  in  the  veins  is  ])'i)eiy  a  physical  plienomenon.  If  fluids,  i, 
which  are  suspended  finely  poAvdered  substances  of  dillereut  specitic  gravity,  are  niai' 
to  flow  through  tubes,  it  will  be  found  that  at  a  certain  degree  of  retardation  of  tl' 
current,  the  bodies  of  lighter  specific  gravity  pass  over  into  the  peripheral  zone,  and  .•. 
a  more  marked  retardation  the  heavier  bodies  also  enter  this  zone.  ; 

For  the  (icenrrence  of  the  emigration  of  the  wlnte  corpuscles,  it  is  necessarl 
according  to  the  researclies  of  lliiis,  Thnimt,  and  Li(ntoirsl,ii,  that  they  be  capable  Ij 
motion  and  of  atlhering  to  the  vessel- wall.  According  to  tliese  observers,  the  emigrj 
tion  of  the  Avhite  blood-cells  is  not  a  purely  passive,  but  is  in  part  at  least  an  acti'j 
process.  If  the  amoeboid  power  of  the  white  cells  be  lessened  by  means  of  irrigati(; 
of  the  mesentery  with  a  1.5-per-cent.  solution  of  .salt  {Thouut),  or  if  the  vital  ener; 
of  these  cells  be  lowered  by  means  of  quinine  or  iodoform  {Binz,  Appert,  Jurm 
there  residts  an  inhibition  of  emigration.  On  the  other  hand,  Pekciharing  belie v 
that  quinine-,  oil  of  eucalyptus,  and  salicylic  acid  cause  a  contraction  of  the  veir 
lessen  the  iiermeability  of  their  walls,  and  thereby  hinder  the  passing-out  of  the  wh ' 
cells.  Tliis  vieAV  is  rejected,  however,  by  Disselhorst,  who  observed  a  dilatation  j 
the  veins  after  irrigation  of  the  tissues  with  quinine,  carbolic  acid,  salicyhc  acid,  ai 
mercuric  chloride.  As  there  occurs  in  this  case  a  retardation  of  the  current  afterj. 
transitory  acceleration,  without  an  emigration  of  the  leucocytes  collected  in  the  perij:  ■ 
eral  zone;  and  as,  on  the  other  hand,  leucocytes  from  blood-vessels  that  have  been  iij- 
gated  for  an  hour  with  quinine  still  retain  complete  vitality  (Eberth),  Disselhorst  is  of  Ij! 
opinion  that  the  drugs  mentioned  so  change  the  inflamed  vessel-wall  that  an  adhesionj! 
the  leucocytes  rolling  along  the  wall  either  cannot  occur  at  all  or  only  with  ditticultjj 

It  is  very  probable  that  a  lesion  of  the  vessel-wall  is  not  absolutely  necessary  [* 
the  emigration  of  leucocytes  ( Thoma).  Since  va.somotor  disturbances  of  the  circulatji 
can  produce  migration  {von  liecMinghausen,  llwrna),  it  is  probable  that  all  of  the  cj- 
ditions  necessary  for  this  process  are  furnished  by  a  slowing  of  the  blood-stream  wjl 
peripheral  disposition  of  the  colorless  corpuscles  and  the  ability  of  the  leucocytesp 
perform  amceboid  movements  and  to  adhere  to  the  vessel-walls.  It  is  possible  tjt 
differences  in  the  water-content  of  the  tissxies  {Tlionia)  also  exert  some  influence,  si!e 
an  increased  amount  of  water  causes  increased  amceboid  movement.  It  is  also  possije 
that  the  presence,  in  the  tissue-fluids,  of  substances  having  active  chemotactic  proj'- 
ties  may  cause  emigration  of  those  leucocytes  in  the  peripheral  zone  which  are  adheilt 
to  the  vessel-wall.  i 

According  to  the  investigations  of  Arnold,  Thoma,  and  Engelmann,  there  is  pres,it 
between  the  edges  of  the  endothelial  cells  a  soft  cement-substance  which  suffers  a  chaifl 
in  the  circulatory  disturbance  associated  with  cell-migration.  This  change  may  so|3- 
times,  but  not  always  {Lowit),  be  recognized,  on  histological  examination,  in  the  fiin 
of  numerous  circumscribed  widenings  of  these  intercellular  areas  (Engchnana).  If  ji- 
cocj'tes  pass  through  these  places  in  great  numbers  the  cement-substance  becomes  U 
more  permeable,  and  may  then  permit  also  lymphocytes  and  red  cells  to  I'^s 
through  in  rapid  succession  {Thoma). 

Wandering  cells  are  found  normally  in  many  tissues  {von  Becklinghausen),  "id 
wander  from  these  partly  into  the  lymph-vessels  {Bering,  Thoma),  and  under  ceijin 
conditions  also  into  tiie  blood-vessels  {Ihibnoff,  Hchulin,  Rnnricr,  Senftkhen),  or  ontcbe 
surface  of  tlie  mucous  membranes,  where  they  penetrate  between  the  epithelial  C;ls. 
They  an;  foimd  constantly  in  large  numbers  about  the  nodes  of  lymphadenoid  ti,Ue 
in  the  uuicous  membranes,  and  wander  from  these  through  the  epithelium  outoiiie 
surface.  According  to  observations  by  Kunkel  and  ISiebel,  small  number*  also  reaclie 
free  surface  of  the  alveoli  of  the  lungs.  I  j 


THEORIES    OF    IM  LAMMATIOX.  325 

The  inflainmatory  (listurhiUKOs  of  circulation  and  tiic  formation  of  exudates  may 
be  most  easily  followed  in  tlu;  transparent  membranes  of  cold-blooded  animals,  jmrticii 
tlarly  in  the  mesentery-,  or  the  extended  tongue  or  the  spread-out  web  of  the  frog.  In 
tthe  frog's  mesentery,  which  has  been  spread  out  on  a  suitable  glass  plate,  circulatory 
disturbances  and  intlanunation  develop  simply  through  exposure  to  the  air  and  the 
resulting  evaporation:  in  the  case  of  tlie  tongue  and  welt,  it  is  necessary  to  cauteriz<"  iu 
iirderlo  produce  an  intlammalion.  By  the  employment  of  suitaitle  apparatus  tiie  cir- 
'culation  of  the  blood  and  the  formalion  of  tiie  inllanunatory  exudate  may  also  be  ol)- 
served  under  the  microscope  in  the  thin  membranes  of  mammals  (mesentery  of  rabbit, 
wing-membrane  of  bat),  and  observations  thus  made  liarmouize  wholly  with  those  made 
upon  the  frog. 

!  The  modern  conception  of  intlammation  is  that  it  is  a  ixdhohxjii'nl  compler  esuentioll}! 
adaptive.  pr->f)Cf/rfi.  and  repurdtlvc.  raUed  into  dftimi  hi/  ,i  j>riiji<ir>/  tinKue-lesioii.  For 
a  presentation  of  this  view  see  Wart/u'n,  Chapter  on  Intlannnatiou,  "American  Practice 
of  Surger\-,"  Vol.  I. 

Literature. 

(Lijfaiiimation.) 

Brault :  Etude  sur  I'inflamniatiou,  Paris,  1888. 

Colinheim  :  Ueber  Entziindung  und    Eiterung.     Virch.  Arch.,  40  Bd.,   1ST6;   Neue 

L'utersuchungen    liber     Entziindung,   Berlin,    1873;    Noch  einmal   die   Keratitis. 
I        Virch.  Arch.,  61  Bd.,  1874;  Vorles.  iiber  allg.  Pathologic,  Leipzig,  1882. 
Cornil  et  Ranvier  :  Man.  d'histol.  patholog. ,  i.,  Paris,  1901. 
Councilman:  Intlammatiou.     Ref.  Handb.  of  Med.  Sciences,  2d  ed.,  1902. 
Heinz:  Experimentelle  Pathologie,  1.,  Jena,  1904. 

Hektoen  :  Old  and  ^Modern  Theories  of  Inflammation.     Phil.  Med.  .Tour.,  1898. 
Henle  :  llaudb.  d.  ration.  Pathologie,  Braunschweig,  1844. 
Janowski  :  Die  Ursachen  der  Eiterung      Beitr.  v.  Ziegler,  xv. ,  1894. 
Landerer  :  Zur  Lehre  von  der  Entziindung.     Volkmauu's  Samml.  kl.  Yortr.,  Xo.  259, 

1885;  Die  Gewebsspannung,  Leipzig,  1884. 
Leber:  Die  Entstehuug  der  Eutzundung,  Leipzig,  1891. 
Letulle  :  L'lutiammation,  Paris,  1893. 

Lubarsch:  Entziindung.    Ergebn.  d.  allg.  Path.,  iii.,  1897;  Deut.  med.  Woch.,1898. 
Messing:  Entziindung  bei  wirbelloseu  Tieren.    C.  f.  a.  P.,  xiv.,  1903. 
Metschnikoff:  Leg.  sur  la  pathologie  comparee  de  Finflammation,  Paris,  1892. 
Neumann:  Ueber  den  Entzlindungsbegriflf.     Beitr.  v.  Ziegler,  v.,  1889. 
Tonfick:  Die  EntwicUelung  der  Entziindungslehre  im.  19.  Jahr.     Berl.  klin.  Woch., 

19(11). 
[v.  BrBcklinghausen :  ILindb.  d.  allg.  Path.  d.  Kreislaufs  u.  d.  Ernaiirung,  Stuttgart, 
'        lHs:i 

'Rokitansky:  Lehrb.  d.  i)ath.  Anatomic,  "Wien,  1855. 
Roser,  K. :  Entziindung  und  llellung,  Leipzig,  1886. 
Ribbert;  I  his  palliolngische  Gewebswachsthum,  Leipzig,  1896. 
Bamuel:    Der   Entzundungsprocess,   1873;    Entziindungsherd   und   Entzimdungshof. 

Virch.  Arch.,  12\  Bd. ;  Ueber  aniimische,  hyperiimische  u.  ncurotiscln*  Entziindung. 

lb..   121  Bd. ;  Die  Selbstheilung  der  Entziindungeu  uud  ihre  Grenzen.     lb.,  126 

Bd.,  1891. 
Schmaus:  Analysed.  Entzundungsbegriffes.    Pestschr.  f.  Bollinger,  "Wiesb.,  1903. 
Thoma:  Ueber  die  Entziindung.     Berl.  klin.  Woch.,  1886;  Pathol.  Anat..  i..  1894. 
Virchow:  Cellularpathologie  u.  Ilandb.  d.  spec.  Path.,  i.,  1854;  Die  liolle  der  GefUsse 

uiid  des  Parenchyms  bei  der  Entziindung.     Virch.  Arch.,  149  Bd.,  1897. 
Weiss:  Beitrilge  zur  Entziindungslehre,  Wien,  1893. 
Woronin    Untersuehungen  liber  die  Entziindung,  3Ioskau,_1897. 

Ziegler:  llistorisches  u.  Kritisches  iiber  die  Lehre  von  der  Entziindung.  Beitr.  v. 
'        Ziegler,  xii.,  1892:   f:ntziindung.     Eulenburg's  Realencyklop.,  vii.,  1S95;   Inllam- 

niation.  Twentieth  Century  Practice  of  Medicine,  xvi.,  New  York,  1899. 

{Griffin  of  the  Exudate.) 

Appert:  Der  Einfluss  des  Chinins  auf  die  Auswanderung  der  wcissen   Blutki'trperchen 

i        bei  der  Entziindung.     Virch.  Arch..  71  Bd.,  1877. 

Arnold:  l.'elur  Diapedese.  Virch.  Arch.,  58  Bd.,  1873;  Ycrhalten  der  Blutgefilsse 
bei  der  Emigration  weisser  Blutkorper.  lb..  62  B.I.,  1875;  Ueber  die  KiltMibstanz 
der  Endolhelien.     lb..  66  Bd.,  1876;  Saftbahnen  des  P.indeirewel.es.     lb.,  6M  Bd., 

Binz:  Der  Antheil  des  Sauerstoffes  an  der  Eiterbildung.  Virch.  Anh..  59  Bd.,  1S74, 
and  73  Bd.,  1878;   Verhalteu  der  Auswanderung  farbloser  Blutzellen  zum  Jodo 


326  ixflam:\iation. 

form.     lb.,  89  Bd.,   1883;   Zur   Salicylsiture- unci  Chinin-wirkung.     Arch.  f.  exp.  | 
Path.,  vii.,  1877;  Uober  einige  Wirkungen  iltherischer  Oele.     lb.,  viii.,  1877. 

Borisow:  Clieinotakt.  Wirkung  versch.  Subst.     Beitr.  v.  Ziegler,  xvi.,  1894. 

Bunzel:  Eintluss  d.  vasomotor.  Nerven  auf  die  Eutziindung.  Arch.  f.  exp.  Path  37 
B(l.,  1896. 

Cohnheim:  L.  c,  Untersuchungen  liber  die  emboiischen  Processe,  Berlin,  1872. 

Dekhiiyzen:  Ueber  Emigration  v.  Leukocyten.     Verli.  d.  Anat.  Ges.,  Jena,  1891. 

Disselhorst;  Emigration  farbioser  Zellen  aus  dem  Blute.     Yircli.  Arcli.,  113  Bd.,  1888.  ■ 

Engelmann :  Yerh.  d.  Blutgefassendotliels  bei  Auswauderung  farbl.  Blutkorp.  Beitr,  • 
V.  Ziegler,  xiii.,  1893. 

Goeclce:  Exper.  Entziindung  der  Hornhaut.     lieitr.  v.  Ziegler,  xx.,  1896. 

Hauser:  Entsteh.  d.  fibrinoseu  Exsudates  bei  d.  croupbseu  Pneiimonie.  Beitr.  v 
Zieiiler.  xv.,  1894. 

Heidenliain:  Ueber  Lymphbilduug.  Verb.  d.  X.  iuternat.  med.  Congr.,  ii.,  Berlin, 
1891;  llistologie  II.  Physiologic  d.  Diinudarmschleimhaut.  Arch.  f."d.  ges.  Phys., 
43  Bd.,  Suppl.-irleft,  1888;  Vcrsuche  u.  Fragen  zur  Lehre  v.  d.  Lymphbilduug.  'lb. 
49  Bd..  1891. 

Heinz-  Entzliudvmg  seroser  Haute.     V.  A.,167Bd.,  1903. 

Hoffmann,  F.  A.:  Ei\veis.sgehalt  der  Ascitesfllissigkeiten.  Virch.  Arch.,  78  Bd., 
1S79. 

Klemensiewicz  :  Fundamental versuche  liber  Transsudation,  Graz,  1883;  Entziin- 
dung u.  Eiterung.  Festschr.  f.  Rollet,  Jena,  1893  ;  Bau  u.  Funktion  d.  Wander- 
zellen.      B.  v.  Z.,  xxxii.,   1903. 

Kronacher :  Die  Aetiologie  u.  d.  "Wesen  der  acuten  eiterigen  Eutziindung,  Jena, 
1891. 

Lassar  :  Ueber  Oedem  u.  Lvmphstrom  bei  der  Entziindung.  Virch.  Arch.,  69  Bd.  • 
1877.  '  ; 

Lavdowski  :  Auswanderung  farbioser  Blutelemente.  Yirch.  Arch.,  96  Bd.  ;  Die  Aus, 
wanderungd.  Leukocvtcu  u.  die  I'rai^e  nach  dem  Schicksale  derselben.  lb.  ,97Bd.• 
18S4.  '  ■  ' 

Lowit ;  Bezieh.  d.  Blutgefiissendothels  zur  Emigration.  Beitr.  v.  Ziegler,  xvi.; 
1894.  : 

Middeldorpf  u.  Goldmann:  Exp.  Untersuchungen  lib.  Croup  u.  Diphtheric,  Jena,' 
l^itl.  '  i 

Pekelharing' :  Diapedese  d.  farblosen  Blutkorp.  bei  d.  Entziindung.  Yirch.  Arch 
104  Bd.,  1886. 

Ranvier:  Traite  techn.  d'histologie,  Paris,  187.5-88;  Beitrag  z.  Lehre  v.  d.  Entziindun 
u.  din  (labci  auftretenden  corpuscularen  Elemeuten.     Virch.  Arch.,  72  Bd.,  1878. 

V.  Reckling-liausen-  Das  Lymphgefiisssystem.  Strieker's  Handb.  d.  Gewebelebn 
Ueber  Liter  und  Eiterkorpercheu.     Virch.  Arch..  28  Bd.,  1863. 

Ribbert:  Zui  Anatomie  der  Lungenentzlindung.     Fortschr.  d.  Med.,  xii.,  1894. 

Schklarewski:   Zur  Extravasation  der  weissen  Bluthorperchen.     Pflliger's  Arch.,  i 

Siebel :  Ueb.  d.  Schicksal  v.  Fremdkorpern  in  d.  Blutbahn.  Virch.  Arch.,  104  Bd 
1^86,  j 

Stdhr  :   Ueber  Maudeln  u.  Balgdrlisen.     Yirch.  Arch.,  97  Bd.,lS84. 

Thoma  :  Entzlindl.  IStorungeu  d.  Capillarkreislaufs  bei  Warnibllitern.     Virch.  ArcL 
74  I'd.,  1878;  Die  Ueberwanderung  farbioser  Blutkorper  v.  d.  Blut- in  d.   Lympj 
irelilsssystem,  Heidelberg,  1873;  Entzlindl.   St  or.  d.  Kapillarkreislaufs  bei  Warri 
bllitern.     V.  A.,  74  Bd.,  1S78. 
See  also  §§  90-93. 

§  90.  The  cellular  and  fluid  exudates  secreted  by  the  vessels  collect  fir 
in  the  immediate  neighborhood  of  the  vessels  (Fig.  189),  but  soon  sprej 
out  in  the  vicinity,  mass  themselves  in  the  lymph-spaces  of  the  tissue,  ai 
thus  form  a  tissue=infiltrate  (Figs.  190,  e;  191,  h:  194,  p).  A\aien  tf 
exudate  is  very  abundant  it  may  spread  into  and  infiltrate  the  ueighbc) 
ing  sound  tissue  tluit  has  not  been  injured  by  the  inflammatory  irritari 
This  infiltration  may  be  so  marked  that  new  disturbances  of  circulati  i 
and  nutrition  n)ay  be  produced,  and  the  area  of  tissue-degeneration  al 
inflammatory  exudation  becomes  increased  in  exteid. 

The  exudate -present  in  a  tissue  may  be  in  part  absorbed  by  the  tissi; 
elements,  so  that  they  become  swollen,  separated  from  their  surroundin* 


TISSUE-LESIONS    IN    IXFLAM.M  A TK  )\ 


327 


I  (Fiji'.  100,  r,  (1),  and  not  rarely  contain  drops  of  fluid  {d)  which  aic  voui- 
nionly  designated  vacuoles.     There  often  occurs  also  a  coini)h'te  dissolu- 


3  ^   *<;^s^ 


G.  190. -Recent  purulent  meninj^ritis  (Miiller's  fluid,  b:oniatoxylin).    a,  Arachnoid  ;  h,  subarachuoideal 
tissue  ;  c,  d,  desquamated  eudollieliuiu  ;  c,  pus-corpuscles.     X  300. 


tion  of  the  tissue=elements  in  the  exudate,  especially  of  the  connective- 
tissue  cells  (Fig.  192,  d,f),  and  not  infrequently,  also,  of  the  intercellular 


]  Fig.   191.  -II;eiiiato(renous  staphvlococcus  myositis    'Micohol.   h;vtniit<>.\vlln-eosin).      n.  TnmsverM'lv  cut 
iiiiisclc-lumdl.'s;  /»,  jiunilem,  c,  scropiinili'iil,  piirlly  i-.iariil.iKMl  i'.\iid;il.-.         4.".. 

substance.     In  thisAvay  both  brain  and  muscle  tissue,  as  well  as  (»rdiiiary 
connective  tissue,  may  become  comi)letely  li(iuciied  in  the  (-ouisc  <»f  in- 

!  flammation,  but  this  liappens  only  when' the  ti.ssue  lias  been  killed  as  a 

I  result  of  the  tissue  injury. 

i        If  dead  cells  become  saturated  with  lymph  containing  libiinogen,  and 


328 


ixflam:matiox, 


if  tibriu-fermeiit  is  formed,  the  liciuefaction  of  the  iuliltmted  tissue  may; 
be  preceded  by  a  coagulation,  wheieby  tiie  cells  becoiiie  ehauged  partly 
into  homogeneous  masses  without  nuclei,  and  partly  into  granular  and 
fibrillar  masses. 


^■^«    / 


:^vr 


J;      ^A'«- 


l^f 


■->^.  -v^i^!- 


Fig.  192.— Section  through  the  border  of  a  blister  caused  by  a  bum  (alcohol,  carmine"),  o,  Hom'j 
layer ;  7),  rete  Malpighii ;  c,  normal  papilla? ;  (?,  swollen  cells,  some  of  whose  nuclei  arc  still  visible  thoug  ■ 
pale,  while  others  have  been  destroyed ;  c,  interpapillary  epithelial  cells,  the  deciiei- 1  mes  intact,  those  of  th ; 
upper  layers  are  drawn  out  lona-itudinally  and  in  part  are  swollen  and  have  lust  their  nuclei;  /,  totjj 
liquefaction  of  the  cells ;  (/,  interpapillary  cells,  without  nuclei,  swollen  and  raised  from  the  cutis ;  /i,  toUj 
degeneration  of  interpapillary  cells  whicli  have  been  raised  from  the  cutis ;  li,  coagulated  e-xudate  (flbriw 
lying  beneath  the  uplifted  epithelium ;  i,  flattened  papillte  infiltrated  with  cells.    X  150. 

If  the  exudate  within  an  organ — for  exami^le,  in  a  muscle — lies  chiefl; 
iu  the  supporting  tissno,  Avhile  the  specific  parenchyma  appears  lint  littlj 


1.-  -  ^_ "- 


.-  a 


Fk;.  193.— Parenchymatous  hepatitis  (Flemmine's  solution,  safranin).   a.  Liver-capsule:  7f,  liver-rods sh 
ing  fatty  degeneration ;  c,  liver-cells  showing  total  degeneration.    X  300. 

changed,  the  inflammation  is  designated  as  an  interstitial  inflammatic 
(Fig.  101,  h).     If,  on  the  other  hand,  the  degeneration  of  the  speci) 


I 


VAliIP:TIES    OF    IMLA.M.MATIO.N.  329 

tissue— i.e.,  the  epithelium  of  tlie  kidney  tubules,  the  liver-cells  (Fij-j. 
llJJS,  />,  (■),  or  the  eoiitructile  substance  of  the  muscles — isthcmost  i)rom- 
iiicnt  Teat n re  of  the  process,  the  condition  is  called  a  parenchymatous 
inflammation. 

When  the  seat  of  an  inflammation  is  on  the  surfac*'  of  an  oiiian,  it  is 
termed  a  superficial  inflammation  (Fio;.  194).  Jf  the  exudate  j^ains 
fi-ee  access  to  the  suiface  and  flows  from  the  same  mixed  with  des<|ua- 
mated  jmrtions  of  the  tissue  (Fij;-.  194,  d,  (',/,/„  g,  h),  the  inflammation 
:is  calleil  a  catarrh.  If  the  pouring  out  of  a  fluid  exudate  (Ui  the  surface 
of  the  skin  or  mneons  membrane  is  hindered  by  a  cohei'cnt  horny  epithe- 
lial layer  (Fig.  192,  a),  and  if  beneath  this  covei'ing  thei-e  ai'c  formed  cir- 
cumscribed collections  of  fluid,  in  which  the  deeper  and  softi'r  layers  of 


red 


\  Fig.  191— Mucous  catarrh  of  a  bronchus  (Muller's  fluid,  anihn(  brown)  a  (iliaUrt  epithelium:  »,. 
•deeper  cell  1  lycs  h  jroblit  cells  c  cdK  showinj?  nnikfil  iiiikous  fit  <r<  nt  rition  (,  iiukokI  cellswiili 
iiiiucoid  nuf  It  I  /  rl  •«  ]  i  nii  it(  1  iiu  )il((lls  i  d  mjh  iiii  itc  1  ( iliiK  d  ( ( lis  1  1 1\<  is  (  f  dn  ps  <if  mucus: 
/,.  layer  (■(  iiMMii   '     f  tli    i  l\  uiu  us    iii  I   |   i        uisls      /    In  t     f  tiu     us  _l  nil  nil    I  \MIIi  iiiim-ms  jiiid 

icells:  /i,(l.  s  111   11   It    I    I  III     h  III    fllii     \  I    1     \   111  t      I    mil   I     I  Hi I       fill     In  t     /    su    lli'ii  liyalinc 

i)iasement-iii  ml  i  iii<      /       im  <ti\(  tnsik      f  tli     ii  ik    si    millii  iii  1  \miIi  nils  iii  i  irt     in   cliliii'dlil I- 

ivt'ssels;  /I,  miKous  fr|  iiKi  tllNdwilli  mudis  /i,  lobule  of  muc  ous  tri  ind  wuliout  iiiui  lis  (  waiidfiluK 
jrellsln  epithelium,  j>,  clHuUi  iiitlltrition  of  the  connective  tihssuc  of  the  mucous k1  mds  110 

the  epithelium  dissolve  (Fig.  192,  d,/,  //,  h),  the  lesions  thus  i»rodnc<Ml 
are  called  vesicles  and  blisters.  When  the  exudate  from  serous  surfaces 
••'•llects  in  the  body  cavities,  thei-e  are  formed  in  the  latler  inflammatory 
;effusions,  which  not  rarely  reach  a  very  large  si/e,  disleiid  llie  affected 
|cavity,  and  compress  the  organs  contained  Avithin  it. 

It  is  customary  to  express  the  occuirence  fif  an  inflammation  of  an 
organ  by  achling  the  termination  ''?7/-s"  to  the  Greek  name  of  the  organ. 
Thus,  for  example,  are  formed  the  terms  endocarditis,  myocarditis,  jjcri- 
ciirditis,  ])leuritis,  peritonitis,  encephalitis,  i)haryiigilis,  keratitis,  orchi- 
itis,  oophoritis,  colj)itis,  metritis,  hepatitis,  nephiitis,  amygdalitis,  glos- 
sitis, and  gastritis.  The  ending  'Mtis"  is  also  sometimes  aflixed  to  the 
r.atin  names,  as,  for  example,  conjunctivitis,  tonsillitis,  and  vaginitis. 
'To  denote  an  inflammation  of  the  serous  covering  of  an  organ  or  of  the 


330  INFLAMMATION. 

tissues  immediately  about  it  the  prefixes  "peri"  and  "para"  are  placed 
before  the  Greek  names  with  the  termination  "itis."  Thus,  for  example, 
are  formed  the  words  i^erimetiitis,  parametritis,  periproctitis,  perityph- 
litis, paranephritis,  and  perilicpatitis. 

For  certain  forms  of  intiamination  especial  names  are  used,  as,  for 
example,  inflammation  of  the  lungs  is  called  pneumonia,  and  iuflamma- 
tiou  of  the  palate  and  tonsils,  angina. 

Since  Colmheim  taught  that  the  migration  of  leucocytes  en  masse  is  an  important- 
feature  of  inflammation  and  serves  as  a  source  for  the  cells  in  the  exudate,  the  ques- 
tion of  the  origin  of  the  cells  present  in  the  exudate  of  acute  inflammations  has  been; 
many  times  the  subject  of  discussion.  While  some  have  regarded  all  the  cells  in  tht! 
exudate  as  extra vasated  leucocytes,  oWiers  have  held  that  the  leucocytes  arising  froni 
the  blood -stream  form  only  an  unessential  element,  and  that  the  main  part  of  the  cells  j 
in  the  exudate  have  arisen  on  the  spot  from  the  tissue  "irritated"  by  the  cause  of  th(i 
inflammation.  ' 

Strieker  held  the  opinion  that  the  swelling  and  hardening  of  the  tissues  in  inflanima 
tion  are  not  caused  by  tlie  collection  of  exudate,  but  by  the  swelling  of  the  cell-reticulun: 
which  was  thought  to  traverse  the  tissues ;  and  that  these  changes  represent  a  pheuoinc; 
non  of  groAvth  of  the  cells  and  their  processes  which  is  characterized  bj'  swelling.  Th 
cellular  exudate — that  is,  pus — he  accounts  for  partlj^  through  the  segmentation  am! 
division  of  the  cell-reticulum  swollen  by  the  inflammation,  and  partly  through  a  trans 
formation  of  connective-tissue  librilla;  into  pus-corpuscles.  Heitzmnnn  regarded  th 
inflammatory  tissue-changes  as  a  reversion  of  the  tissue  to  the  embryonal  condition,  an 
believed  that  the  living  material  is  not  contained  in  the  cells  alone,  but  infiltrates  th 
entire  ground-substance,  and  increases,  in  the  progress  of  an  inflammation,  with  th 
liquefaction  of  the  ground-substance.  Connective-tissue  cartilage  and  bone  beconi 
resolved  during  inflammation  into  those  elements  from  Avhich  Uiey  are  formed — i.e 
into  cells — which  then  immediately  reproduce  their  kind.  Gramtz  believes  that  bot 
the  cellular  infiltrate  and  pus  are  formed  without  any  participation  of  the  leucocyte 
worth  mentioning.  Everywhere  in  the  tissue,  according  to  his  view,  there  lie  conceale 
in  gi'eat  numbers  cells,  which  he  designates  slumber-cells,  and  which  are  not  affecte 
by  our  nuclear  stains  and  therefore  not  recognizable  (according  to  him,  only  from  fi\ 
to  ten  per  cent,  of  the  tissue-cells  are  knowm  to  us) ;  these  cells  awake  in  inflanunatioi 
and  again  come  into  sight — that  is,  increase  in  size,  stain  with  nuclear  stains,  and  ther 
fore  again  become  recognizable. 

According  to  the  results  of  an  imprejudiced  and  careful  examination  of  inflam* 
tissues,  there  can  be  no  doubt  that  the  description  of  the  origin  of  the  inflammatory  i: 
filtrate  given  by  Strirlrr,  ITcHzninn-H,  Grawitz,  a,nd  their  pupils,  does  not  correspond 
the  coiKlitidns  as  tlicy  aftually  exist.  The  cells  which  lie  in  recently  inflamed  tiss 
cniisisv  in  i)art  (if  ieucocyles  which  have  wandered  from  the  vessels  and  in  part 
tissue-cells  wliich  are  more  or  less  degenerated,  and  are  often  separated  from  the  undf 
lying  tissues.  Later,  to  these  there  are  added  newly  formed  cells  which  have  arisi 
through  the  division  of  preexisting  tissue-cells. 


i 


Literature. 

(The  Processes  Occurring  in  the  Tissiim  during  Inflammation,  and  the  Ori, 
of  the  Cells  in  the  Exudate.) 


Baumgarten :  ITerkunft  d.  in  Entzlindungsherden  auftret.  lymphkorperart.  Elemeu 

Cbl.  1.  allg.  Path.,  i.,  1890.  ' 

Bottcher:  Entstehung  der  Eiterkorperchen  bei  der  traumati.schen  Keratitis.     Vinl 

Arch.,  58  Bd.,  1873;  Ueber  die  circumscripte  Keratitis.     lb.,  62  Bti.,  1875. 
Cattani :  Ueber  die  Reaction  der  Gewebe  auf  specifische  Reize.     Beitr.  v.  Zieglcr,  v  , 

1891. 
Coen:  Veriinderungen  der  Haut  nach  Einwirkung  von  Jodtinctur.     Beitr.  v.  Ziegli, 

ii.,  18H7. 
Ebertli:  Entziindung  d.  Hornhaut.     Unters.  a.  d.  path.  Inst,  in  Ziirieh,  Leipzig,  111 

and  1875;    Kern- u.  Zelltheilung  bei  Entziindung.     Internat.  Beitr.,   Festschr. . 

Virchow.  ii..  Berlin,  1891. 
Grawitz  :  DieEntwickclung  der  Eiterungslehre.     Deut.  med.  Wocli.,  1889;  Histol  . 

Vcriiiulerungen  bei  der  eitrigen  Entziindung.     Virch.  Arch.,  118  Bd.,  1889;  At:3 


VARIETIES    OF    IXFl.A.M  M  A  TION  , 


WAX 


^yy 


(Icr  piithol.  Gewcbelehre,  Berlin,  1893;  Eutzundmi^r  d.  llornlnuit.     Yirdi.   Arch 

144  Bd.,  isim. 
Griinwald  :  Zilk'u  im  Auswurf  u.   entzundl.    Ausscliwitzungcn.     Viirli.    Anli       \~)S 

15(1.,  18!)9. 
Key  II.  Wallis  :  Exp.  Unters.  i'lb.  d.  Ent/iiiidun£^  d.  llornliaut.     Vircii.  Arch.,  .">  Ud.^ 

\s:-2. 

KrafFt :  Zur  llistogenese  des  periostalen  Callus.     Beitr.  v.  Zieglcr,  i.,  ISSO. 

Marchand  :  Unteisuch.  liber  die  Einheiluug  vou  Fremdkorpeni.     Beit.  v.    Zicgler, 
iv..  ISSS. 

Neumann  :  Variabilitiit  der  Leukocyten.     Vircli.  Arch.,  174  Bd..  1903. 

NikiforoflF:  Ban  u.  Entwickeluug  des  Granulatiousgewebes.     Beitr.  v.  Zicglcr,  viii., 
1S!)0. 

Pappenheim  :  Einkornige  Zellcn  in  gonorrlioischen  Sekret.     V.  A.,  164  Bd.,  1901. 

Podwyssozky  :  Regeneration  der  Driisengewebe.     Beitr.  v.  Ziegler,  i.,  ii  ,  1884-88. 

Roemer  :  Die  ciiemische  Reizbarkeit  thierischer  Zellen.     Virch.  Arcii.,  12S  Bd.,  1S<)2. 

Strieker:  Studieu  a.  d.  Institute  f.  exp.   Pathologic,  Wien,    1S70;  Veisciiicd.   Auf- 

siitze  in  den  Wiener  nied.  Jaiirl).  a. 
(1.  J.  1871-83;  Allgeni.  Patholo- 
gic, Wicn,  1877-83. 
Weigert :  Die  Virchow'sehe  Entziin- 
(lunustlicoric  u.  d.  Eitcrun>;slehre. 
Fortsclir.  (1.  ^Icd.,  vii.,  ISSi). 
Wlassow  u.  Sepp  :  Eniiiiration  der 
Lvmphocvtcn.  V.  A.,  176  Bd., 
1904  (Lit.). 
Ziegler:  p^xp.  Tntcrs.  iibcr  die  ITcr- 
kiuilt  der  Tuberkelelemcnte, 
Wurzburg,  1875;  Unters.  fiber 
patholog.  Biudegewcbs-  u.  Gefilss- 
neubildiing,  Wiirzburg,  1876; 
Ueber  die  Betheiligung  der  Leu- 
kocyten an  der  Gewebsneubildung. 
Verb.  d.  X.  iuternat.  med.  Congr., 
ii.,  Berlin,  1891;  Ueber  die  Ur- 
saclicn  der  jiathol.  Gewebsneubil- 
dung. Festschr.  1'.  Viicliow,  ii., 
Berlin,  ISJU;  llistorisclies  u.  Erit- 
isches  liber  die  Lehn;  von  der 
Eutzlindung.  Beitr.  v.  Ziegler, 
xii.,  1892. 
See  also  gg  89,  91,  and  92. 

§  91.     Both   tlie   Jocal  tissue- 
(legene)'ation    and    tlie    exudation 

■\\     '^^'/'W*'*       *?t*?^*V7^ff>1  cases,  and  tlu'iv  "may  be  (list  iii- 

yp'*^^^^:;,'^^^     'y^rrt^O  .U'llshed     accoidiiioly     diU'civnt 

.>,>V.^      ;^/*^//^';'T*';/:;';V»V^  forms  of  inflammation. 

'''•ir''''''.V«iyt'?*    ,'V;'''4'' Iv  *•  'V**'*J^'*'*V^i  it   tlKM'xiuhitc  »'i»iisi.sts  ('ss(Mi- 

^'^•^v.•V.^Jl•  ;t    ,;•  '\''';jj,^^l*'" ' '«V,*^i  l^n" coiistit ucnts  arc  iiisi<;iiilici>iit , 

r^^*\*!i;l'i:V5!.V;f-,\iH  \''i''''   i  ^^  ^•'^   called  a  serous  exudate. 

i    X^'\.-'^-.'\V''yL^''\^'v    .."'rt^/.         a  When  contained  wilhiii  a  lissiu- 

r'J;':rV'v,-.-ic         •.yJ.'/.•.^;."^•         ^  _foi.  (.xaini)lc,  williin  llic  skin 


I  '■beainiii.-iisl.-.s  iMlcohnl,  li;ein;itn\vlin.  nisiiu.  ((.Layer 
I  of  pus-<-(,r|,usclesaiid  UesMUiiiiiiited  .■pitlieliiilil  ;  /Mrilaet 
'deepest  l;iyer  of  epitiieiiuiu  ;  t,  ba.seiiient-iiiembnitie  ; 
I  a,  hypenfmic  and  inflltrated  connective  tissue  of  the 
mucosa ;  e.  inflltrdted  submucosa  with  mucous  glands. 


XIOO. 


and  siilx'iitancons  1issn<',  <>r  in 
the  luiiiis— thcic  rcsnlls  an  in- 
flammatory (t'dema.  I'lic  cs 
ciipc  of  the  liiii.l  on  tlii-  free 
snil'a<'c  ol"  a  niiicoiis  oi-  .sci'ons 
nienil>ranc  .uivcs  the  i)ictnrc  of 
a  serous  catarrh  ;  circunisciibed 
collections  of  llnid  beneath  the 


332 


INFLAMMATION. 


horny  layer  of  the  epidermis  with  the  liquefaction  of  the  soft  layers  of  a. 
epithelium  lead  to  the  formation  of  vesicles  and  blisters  with  clear  con.-  ' 
tents  (Fig.  192,  d,  f). 

When  the  exudation  of  fluid  on  the  surface  of  a  mucous  membrane  is 
associated  with  a  marked  mucoid  degeneration  of  the  sui^eificial  epithe- 
lium (Fig.    104,  h,  c,  cj,  and  of  the  mucous  glands  (»),  there  arises  a 


Fig.  196.— Catarrhal  secretion  of  different  mucous  membranes.  A,  Secretion  from  mucous  membrane 
with  columnar  cells ;  B,  from  the  mouth;  0,  from  the  bladder.  1,  Round  cells  (pus-colls);  ;i,  large  rour, 
cells  with  bright  nuclei,  from  the  nose;  3,  mucoid  columnar  cells  from  the  nose;  4,  spirillum  from  theuosi] 
.'>,  mucoid  cells  with  cilia,  from  the  nose ;  6,  goblet-cells  from  the  trachea;  7,  niuml-cclls  with  spherules  ■ 
mucus  from  the  nose;  S,  epithelial  cells  containing  pus-corpuscles,  from  the  nose;  9,  fatt.y  cells  from, 
chronic  catarrh  of  the  iiliaryn.x  and  lar.vn.v  :  10,  cells  containing  carbon  pigment,  from  the  sputum;  11  aii 
13,  squamous  epithelium  fnun  the  nioutli;  ]:!,  mucoid  pus-corpuscles;  14,  micrococci;  15,  bacteria;  Ij 
leptothri.v  buccalis;  17, siUnicliirtr  dotticala;  18,  superficial,  19,  middle  layer  of  bladder  epitheliUD) 
2(),  pus-corpuscles;  ~1,  .vc/iizo//iiyct'(fS.     X  4t)0.  I 


'mucous  catarrh  (d,  f,  /,,  ff).  If  a  marked  desquamation  of  the  epitbj 
lium,  Avith  or  without  a  mucoid  change,  occurs  (Fig.  195,  a),  the  coud 
lion  is  termed  a  desquamative  catarrh  ;  and  such  a  process  may  occij 
not  only  on  mucous  membranes,  but  also  in  the  respiratoiy  parenchyni 
of  the  lungs,  on  serous  surfaces  (Fig.  189, /,/,),  in  the  kidney-tubule| 
etc.  •  If  many  pus-corpuscles  are  ])resent  in  the  exudate  it  may  be  spok(] 
of  as  a  desquamative  purulent  (Fig.  195,  a),  or  finally  as  a  pure  puri; 
lent  catarrh,  in  Avhich  condition  the  exudate  becomes  white  or  yelloy 
ish-whitc,  milky  or  creamy.  J 

The  form  aiid  character  of  the  cells  of  a  catarrhal  secretion  vary  wi^j 
the  location  and  the  variety  of  catarrh  (Fig.   196).     Bacteria  are  oft(| 


196, 


14,  15,  16,  r. 


',21). 
or  coagul'j 


preseut  in  the  cells  of  the  exudate  (Fi 

If  in  a  fluid  exudate  there  occurs  a  dei)osition  of  fil)rin 
tion,  there  are  formed  fibrinous  and  serofibrinous  exudates,  which  ai 
often  designated  as  croupous.     These  occur  chiefly  upon  the  surface  f 
serous  and  mucous  membianes,  and  in  the  lungs;  but  masses  of  fibri 


VAHIKTIES    OF    I  .\F1>A.MM  A  TK  )\  . 


IV.VA 


I   ill  tissues   iiililtrat('<l  \\itli  oxudatc,  as  moII  as  in  lyinpli 


may  Ih-  t< 
vessels. 

On   the    mucous    uienibranes 
patches  and  coherent  membrane 


the  lihrinous  exudates  form  Avhilish 
which  sometimes  lie  upon  them  only 
loosely,  but  at  olhei-  times  are  lirmly 
attached  to  the  underlying-  surface. 
In  the  serous  ca\  iti«'S  the  iil>iin»»iis 
coa,i;ula  lloat  in  the  form  of  Makes  in 
the  lluid  iioition  of  tlu'  exudate,  or 
form  a  lirmly  attached  dejiosit  upon 
the  surface  of  tlu^  membranes.  Such 
de[)osits  consist  at  times  only  of  thin, 
attached  films  or  <;ranuh's  which 
ii'ive  to  the  wiped-off  surface  a 
cloudy,  lustreless,  rough,  or  gi-anu- 
lar  appearance;  at  other  times  of 
larger  yellowish  or  yellowish-red, 
tirm  membranes,  Avhich  often  give 
to  the  surface  a  felted  oi-  villous 
appearance  (cor  villosum).  In  the 
lung,  croupous  inflammation  leads 
to  a  filling  of  the  alveoli  with  a 
coagulated  mass,  in  consequence  of 
which  the  lung  acquires  a  firm  con- 
sistence. 

On  mucoioi  surfaces  the  foi-mation 
of  croupous  membranes  takes  place 
when  the  epithelinm  is  ali-eady  des- 
quamated and  the  connective  tissue, 
at  least  in  part,  is  exposed;  lint  tis- 
sues covered  with  epithelium  may 
also  become  the  seat  of  fibrinous  d<'- 
posits  extending  fi'om  denuded  areas. 
The  desquamation  of  the  ei)itheliuni, 

in  such  a  case,  may  follow  gradually,  or  at  other  limes  nioie  iai)i(lly 

through  the   lifting   up  of   whole  layers  of  epithelium   (Fig.    107,  h), 

which  are   either   well 

'preserved    or    already 

jdegenerated   or   necro- 

itic,  and  intiltrated  with 

|exudate  (Fig.  199,  a). 

\      The    exudation    of 

Itibrin    may   begin    un- 

jderneath     the     raised- 

jup  epithelium  with  the 

iformation  of  fine 

meedle-like    forms    re- 

•sembling  crystals  (Fig. 

)197,  (1),  which  are  ar- 

J-.mged    radially  about 

(U  centre,    in  Mliich   at 

itiines  there  lies  a  small 

ihody,  probably  a  product  of  the  disintegration  of  a  red  corpuscle,  or  a 

iblood-plate.     Very  soon  there  form  thicker  or  thinner  threads  (Figs. 


Acute  basmorrhagic  fibrinous  in- 
imination  of  the  trachea,  caused  by  vapor  of 
liiiiiinonia  (Miiller's  fluid,  ha?matoxylin,  eosin). 
i'l.  Superflciallayer  of  the  connective  tissue  of 
it  he  mucosa,  with  greatly  dilated  blood-vessels 
land  extravasated  red  blood-cells;  />,  deep  layer 
I'lf  epithelium  raised  up  in  (0(0;  c,  desquamated 
it'pithelial  cells;  d,  ha?morrhagic  flbrinous  exu- 
■  ilate  with  radiating,  crystal-like  masses  of  fibrin, 

in  part  proceeding  from  small,  colorless  sphet- 

ul.?s.    X  300. 


-rf 


6  ^ 


YUi.  198.— Croupous  membrane  from  the  trachea,  a.  Section 
through  membrane;  />,  uppennost  layer  of  the  mucosa  Infiltrat^vl 
with  pus-corpuscles  ((/);  c,  fibrin  tlireuds  and  granules;  r/,  pus-cor- 
puscles. 


rpusi 
2.50. 


334  INFLAMMATION. 

198,  c;  190,  b,  c)  which  enclose  a  larger  or  smaller  number  of  leucocytes 
and  red  blood-cells.  The  arrangement  of  the  threads  is  nsually  reticu- 
lar, but  the  thickness  of  the  network  and  the  size  of  the  meshes  vary 
greatly.  When  there  is  unequal  development  of  the  fibrin  threads  and 
strands,  the  principal  strands  sometimes  lie  parallel  with  the  surface 
of  the  mucous  membraue  (Fig.  198,  c),    sometimes  perpendicular  to  it. 


•  1  '■ 


Fig.  199.— Section  from  an  inflamed  uvula  covered  with  a  stratified  flhrinous  membrane,  from  a  Cf. 
of  diphtheritic  croup  of  the  pharyngeal  organs  (Miiller's  fluid,  ha-matoxvlin.  eosin).  a.  Surface  layer  I 
coagulum,  consisting  of  epithelial  plates  and  fibrin  and  containintr  nuiuennis  cdlonies of  cocci;  b,  seco  1 
layer  of  coagulum,  consisting  of  flne-meshed  fibrin  network  enchisiiiL'-  leiimcvtis ;  c.  third  layer  of  coagulu 
lying  upon  the  connective  tissue,  and  consisting  of  a  wide-meshed  reticulum  nf  fibrin  enclosing  leucocytt) 
rf,  connective  tissue  infiltrated  with  cells;  f,  infiltrated  boundarv  layer  of  the  connective  tissue  of  themuec 
membrane ;  /,  heaps  of  red  blood-cells ;  (/,  widely  dilated  blood-vessels  :  ;/,  dilated  Ijnuph-vessels  filled  w 
fluid,  flbrin,  and  leucocytes ;  »",  duct  of  a  mucous  gland  distended  with  secretion ;  h,  transverse  section  ol 
gland ;  (,  fibrin  reticulum  in  the  superficial  layer  of  connective  tissue.     X  45. 

(Fig.  199,  c).  Thick  fibrinous  membranes  frequently  show  a  distiu! 
stratification  (Fig.  199,  a,  h,  c),  indicating  that  their  formation  has  c' 
curred  in  successive  batches  pushed  up  fi-om  below. 

When  a  mucous  membrane  becomes  the  seat  of  a  deposition  of  fibri 
the  underlying  connective  tissue  is  always  more  or  less  hyj^erfemic  (Fi 
199,  ff),  (Edematous  and  swollen,  infiltrated  with  leucocytes  (Figs.  If. 
d,  e;  200,  e),  and  usually  contains  here  and  there  also  thready  fibu 
precipitates  (Figs.    199,/;  200,  /).     Very  often  the  tendency  to  t; 


FIBKXNOUS    KXUDATTOX. 


335 


Fio.  200.— Croupous  tracheitis.  Section  through  the  connective  tissue  of  the  mucosa  (carmine  and 
Ibrin-staln).  a,  b,  c,  d.  Blood-vessels  with  flbrin  precipitates  :  e,  oedematously  swollen  connective  tissue 
vlth  leucocytes ;  /,  connective  tissue  with  flbrin-threads.    X  500. 


'"lifer     7^     <*o 


r.d 


*.*'f(«».-^=^^ 


Fig.  301.— Traumatic  flbrinopurulent  peritonitis  (alcohol.  Van  Gieson's) .    rt.  Peritoneum  of  the  alxloinl- 

wall;  7>,  serosa  of  a  knuckle  of  i '       '  '    " " *'"■" " 

atact;  d,  e,  flbrin-deposit.    X  'Xm. 


lal  waU;  7a  seTOra"oTa  knuckVe  of  intesYinVwhich'hadb^^^^    sutured  to  Ww  wall ;  r,  epithelium  remaining 


;iO.  202.— Fibrinous  pleuritis  (alcohol.  Van  Gieson's).    a.  Connective  tissue;  7>.  desquamated  epithelium; 
'  c,  thick,  homogeneous,  iJ,  granular  layer  of  flbrin  with  leucocytes.    X  100. 


336 


IJN  FLAMM  ATIO  1\-. 


precipitation  of  fibrin  is  manifested  also  within  the  blood-vessels  (Fig 
200)  inasmnch  as  these  contain  at  times  tangled  threads  and  rods  o: 
fibrm  (Fig.  200,  &),  at  other  times  fibrin-needles  grouped  m  stellat<, 
forms  or  in  clusters  («,  c,  d),  which  often  proceed  from  degeneratec 
endothelial  cells  or  leuco- 
cytes, or  from  blood-plates, 
or  radiate  from  portions  of 
the  vessel -wall  where  the 
endothelium  is  lost.  Like- 
wise, fibrin  -  threads  may 
be  also  found  in  the  dilated 
lymph -vessels,  in  associa- 
tion with  fluid  and  cellular 
exudate  (Fig.  199,  h). 

On  the  serous  membranes 
the   deposits  of  fibrin  ap- 
pear   partly    in    granular 
(Fig.  202,  d)  and  thready 
(Fig.  201,  d,  e),  or  in  thick, 
homogeneous  masses  (Fig. 
202,  c),  or  even  in  the  form 
of  ribbon-liko  bands.    Here 
also  the  epithelium  is  exfo- 
liated at  the  point  of  depo- 
sition (Figs.   201,  d,  e;  202, 
c),  but  may  be  preserved 
in  patches  and  covered  over 
with  fibrin  (Fig.   201,  c). 
The    connective   tissue    of 
serous  membranes  in  croup- 
ous inflammation  is  some- 
times more,  sometimes  less 
infiltrated,   and   may   con- 
tain leucocytes  and  fibrin, 
both  in  the  congested  ves- 
sels themselves  (Fig.  200, 
ff)  and  in  the  connective- 
tissue  spaces  (Figs.  200,  e, 
f;  203,  c).     More  marked 
exudations  of  fibrin   upon 
the  surface  of  serous  mem- 
branes may  ])r()(lu('e  tliick, 
felted  deposits,  the  formed 
elements  of   which  consist 
of  thready  fibrin  and  pus 
corpuscles  (Fig.  203,  d,  e), 
as  M'ell  as  micro-organisms 
(&).    An  abundance  of  i)us- 
corpuscles    gives     to    the 
exudate     a    fiJyrinopurnlent 
character,  the  yellowish  de- 
posits becoming  more  whit- 
ish in  color.  FK    2(W  — Fibrinopurulent  dii  1  tociiis  pkuiitiMii  a  tliretsar 
T7-7     •                    ;j  *       -41       old  child   (fornialin,  flbiin-staln).    «,  Intlamecl  plelml;.■.^iP^o• 
i''<0/•<«OMS  exudates  %n  tlie    cwcl;  c,  tibrin;  d,  6,  flbrinopurulent  exudate.    X  oOO. 


AAHIKTIKS    OF    IXKLA.M.M.Vl'K  )\  . 


:VA7 


Uinffs  are  cliaractcrized  by  Ihe  formation  of  ii  iiioro  or  loss  rloso  network 
of  librin-threads  (Fiij.  L'O-l.  l>),  in  whoso  nioslios  and  in  tlio  ininiodialo 
iieijililx'riioodof  Aviiioli  lie  lonoooytos  and  nsnalls  also  icd  hlood-oolis  (r), 
miuiilod  with  dos(iuanialod  i'i>itli('linin.  In  tho  tirsl  stajios  thoio  are  also 
found  (urasionally  ^lobnlar,  wreath-sliaped  procipitalos  of  lilirin  JoiiuMl 
to«iOthor  in  rows.  Fil)rin-t breads  may  develop  also  in  and  npon  (lta<l 
epithelium  (^Ilauser). 

In  tJie  lidnci/s  deposits  of  fibrin  may  ocour  in  the  form  of  tine  threatls 
or  hyaline  masses  in  the  urinary  tubules  and  i;lomerular  eapsules.  In 
the  himph-iihimU  libi-in-throads  are  formed  partioulaily  in  the  lymj)!!- 
channels. 

Hjemorrhagic  exudate— that  is,  an  exudate  eontaininj;-  lai'<;e  num- 
l)ers  of  rod  cells — ooours  ospooially  in  conneetion  with  Iho  ox.Mlatiou  of 
fibrin.  The  exudate  of  croupous  pneumonia  constantly  contains  it  lar.uoi 
or  smaller  number  of  red  blood-cells  (Fig.  204,  c),  and  likewise  in  librin- 


.^ 


Fig.  afH.-crouiK)Us  pneumonia.    Red  liepatization  of  tlu"  Uiuk  (alcohol,  carmine,  nbrin-staiii). 
trated  alveolar  septa  ;  b,  tlbrinous  exudate  ;  c,  red  blood-cells.     X  3)0. 


ous  pericarditis  and  pleuritis  great  numbers  of  rod  blood-c«'lls  not  infr<'- 
quently  escape  from  the  vessels.  Iliemorrhaojc  inllammalions  occur  not 
infrofpiently  in  the  central  nervous  system,  in  lymi)h-glan(ls,  in  the  skin 
md  kidneys.  In  the  last  case  the  blood  escapes  from  tho  glomerular 
vessels. 

The  serous,  fibrinous,  and  serofibrinous  intlainmat ions  are  caused  l)y 
thermal  and  chemical  influences,  as  well  as  by  bacteria;  Init  are  most 
frequently  the  result  of  infection,  ]»articulaily  (tf  infoction  with  the  7>/>- 
IwoccuH  pncumon'xr.  (Fig.  204,  h)  and  the  Borillus  <lipliflHri<r.  'IMio  I'ormor 
eau.ses  particularly  croupous  inflammations  of  the  lungs  and  j.loura,  th«' 
latter  gives  rise  to  fibrinous  inflammations  of  the  throat,  ])alato,  and 
respiratory  i)assagos. 


338  INFLAMMATION. 

J^''euma)in  liokls  the  opinion  that  in  rrcoif  lihriiiDus  inflammations  of  the  serous 
membranes  the  hj-aline  bands  and  lumps  on  the  surfacr  of  tlic  membrane  are  not  exu- 
dative fibrin,  bnt  represent  layers  of  counectivi'  tissue  that  luive  undergone  a  fibrinoid 
degeneration.  I  cannot  subscribe  to  this  view,  but  agree  rather  with  the  majority  of 
writers  who  have  expressed  opinions  upon  this  subject  that  the  deposits  are  exuda- 
tive fibrin.  The  illustrations  which  yeumrnin  has  presented  in  his  work  are  in  no  man- 
ner confirmatory  of  his  view,  but  enable  us  rather  to  affirm  that  JSeiiriiann  had  before 
him  in  his  preparations  exudative  fibrin. 


Literature. 

{^Catarrhal,   Serous,  and  Fibrinous  Infftmmation,  and  Formation  of  Inflom- 
matory  Elehs. ) 

Abramow:  Fibrinose  Eutziiud.  d.  serosen  Haute.     Beitr.  v.  Ziegler,  xxiii.,  1898. 
Arnold:  ;Morph()l<)gie  d.  extravascul.  Gerinnung.     Virch.  Arch.,  150  Bd.,  1897. 
Baginsky:  Diphtlierie  u.  diphthcritischer  Croup,  Wieu,  1898. 

Baunigarten:  Pathogenese  der  diphtherischen  Membran.     Berl.  klin.  Woch.,  1897. 
Borst:   Fibrinose  Exsudation  u.  fibrinoide  Degeneration.      Zeit.  d.  Phys.-med.  Ges. 

Wiirzburg,  1897. 
Cornil:  Infiamm.  des  membranes  sereuses.     Arch,  de  med.  exp.,  1897. 
Ernst:  Uebcr  das  Vorkommen  des  Fibrins  in  Nierencylindern.     Beitr.  v.  Ziegler,  xii., 

1S93. 
Gay  lord:  Fibrinous  Exsudates.     Jour,  of  Exp.  Med.,  iii.,  1898. 
Georgiewsky :  Fibrin.  Entziind.  seroser  Haute.     Beitr.  v.  Ziegler,  xxv.,  1899. 
Graser:  Die  erste  Verklebuug  seroser  Haute.     Langenbeck's  Arch.,  50  Bd.,  1895. 
Hauser:  Pathol.  Fibringerinnung.     Deut.  Arch.  f.  klin.  Med.,  50  Bd.,  1893;   Entsteb. 

(1.  fibrin.  Exsudates  bei  der  croup.  Pneumonic.     Beitr.  v.  Ziegler,  xv.,  1894;  Gerin- 

nungscentren.     Virch.  Arch.,  154  Bd.,  1898. 
Heinz:  Jod  u.  Jodverbindungeu.     Virch.  Arch.,  155  Bd.,  1899;   Entsteh.  d.  Fibrins. 

Ih.,  1(30  Bd.,  1900. 
Herxheimer :  Fibrinose  Entzlindungen.     Virch.  Arch.,  160  Bd.,  1900. 
Heubner:  Uebcr  die  diphtheritische  Membran.     Jahrb.  f.   Kinderheilk.,  xxx.,  1889 

Verb.  d.  Congr.  f.  inn.  Med.,  viii.,  1889. 
Jatta:    Genese  de  la  fibrine  dans  les  inflam.  de  la  plevre.     Arch.  ital.  de  biol.,  xxxi. 

1898. 
Kossel:  Ueber  Schleim  und  schleimbildende  Stoffe.     Deut.  med.  Woch.,  1891. 
Kramer :  Veranderungen  d.  Rachen-  u.  Kehlkopf schleimhaut  b.  Diphtheric.     Inaug. 

Diss  ,  Freiburg,  1890. 
Marchand:  Fibrinose  Exsudation  bei  Entzlindungen.     Virch.  Arch.,  145  Bd.,  1896.   . 
Middeldorpf  u.  Goldmann:   Exp.  u.   path.-anat.   Unters.   iib.   Croup  u.  Diphtherie* 

.Tena,  IsOl.  ' 

Mviller:    Veriind.  d.  Blutkorp.  bei  extravascul.  Gerinnung.     Cbl.  f.  allg.   Path.,  viii, 

1S97. 
Neumann:    Pikrokarminfarbung  und   ihre   Anwendung   auf   d.    Entzimduugslehn' 

Arch.  f.  mikr.  Anat.,  xviii.,  1880;    Fibrinoide  Degeneration  d.  Bindegewebes  In, 

Entzlindungen.     Virch.  Arch.,  144  Bd. ;  Fibrinoide  Degeuerat.  u.  fibrin.  Exsud; 

tion.     lb.,  146  Bd.,  1896. 
Oertel:  Pathogenese  der  epidemiselien  Diphtlierie,  Leipzig,  1887. 
Ribbert:  Zur  Anatomic  der  Lungeiient/.iindung.     Fortschr.  d.  Med.,  xii,,  1894. 
Salty kow:  Entzlindungen  der  seiijsen  Hilute.     Beitr.  v.  Ziegler,  xxix.,  1900. 
Sudsuki  :  Pathogenese  der  diphtheritischen  Membran.     B.  v.  Ziegler,  xxix.,  1901.   i 
Touton:  Vergl.  Unters.  liber  die  Eutstehung  der  Hautblasen,  Tubingen,  1882.  ! 

Weigert:    Anat.  Beitr.   zur  Lehre  von  den  Pocken,  Breslau,  1874;   Ueber  Croup  i 

Diphtheritis.     Virch.  Arch.,  70  Bd.,  1877;   72  Bd.,  1878;   Ueber  d.  pathol.  Gerij 

nungsvorgange.    lb.,  79  Bd.,  1880;  Methodenzur  Farbung  von  Fibrin.     Fortsclj 

d.  :\ied.,  v.,  1887.  _  ,       ' 

Wlassow:    Die  histol.  Vorgitnge  bei  der  Gerinnung  u.  Thrombose.     Beitr.  v.  Ziegli 

\v.,  1894. 
Zahn:  Bcitrage  zur  pathol.  Histologic  der  Diphtheritis,  1878. 
Zenker:  Intravenose  Fibringerinnung.     Beitr.  v.  Ziegler,  xvii.,  1895. 
Ziegler:  Ueb.  d.  Entziinduug  der  serosen  Haute.     Beitr.  v.  Ziegler.  xxi.,  1897- 

See  also  §i^  89  and  92. 


PURULENT    I N  FLA  M  M  AT  1  ()  \ , 


339 


§92.   When  the  iiillaiimiatory  exudate  is  made   up  cliictly  ol'  Icuco- 
;ytes,  there  is  produced  within  the  tissue  a   small-celled   infiltration 


^^-.G»4. 


■>^v«i.-^vtrvi^.^ii5^ 


I  Fig.  205.— Purulent  bronoliitis,  peribidnotiitis,  and  peribronchial  broncliopncmnonia  in  a  child  one  year 
Id  three  months  old  (Miiller's  tiuiil,  ha^inatoxylin,  eosin).  a.  Purulent,  /),  mucoid  bronchial  contents; 
f,.  bronchial  epithelium  intUtrated  witli  round  cells  and  partly  (le.s<)uainat<'il ;   i/.  inllltrated  bronchial 

.all  with  frreatly  dilated  hi l-vesseis;  r.  inlilliatcd  peribronchial  and  periarterial  connertive  tissue;  /,  al- 

!*olar  septa,  in  part  iiililtratfd  witli  cells  :  (/.  Ilbrinniis  exudate  in  the  al\  roll ;  h.  al\coli  llllcil  with  exudate 
Icb  i!i  cells  ;  i,  ;ii\i'iili  lillcd  with  exutlate  <■>  mtainint:  few  cells:  /, ,  cruss-sccliiiu  "f  a  pulmonary  artery; 
jbronchial,  peribronchial,  and  iuteracinous  vessels  showing  marked  congestion.     ,-,  4;}. 

Figs.  191,  b;  205,  d,  e,  f)  which  under  certain  conditions  may  be  so 
parked  that  the  structure  of  tlie  tissue  is  more  oi-  h'ss  obscured.  If 
\olynuclear  leucocytes  or  pus-cells  are  present  in  large  numbers  in  tlie  tluid 


'fH-^- 


I  Fig.  306.- Section  of  a  smallpox  pustule  (injected  hiBmato.xylln  preparation),  n.  Hornv  layer;  h.  stra- 
,m  mucosum  of  the  epidertnis :  d,  cutis ;  e,  smallpox  pustule  :  /,  cavity  of  the  pock,  contalnintr  at  f^  pu.s- 
ilut""''*t  1  ■  ''■  '"'•''Tapillary  remains  of  epithelium  inQltrat*;d  with  pus-con)uscles ;  A,  papillary  ImkIIcs 
•lurated  with  cells;  i,  umbilication  with  thin  pock  cover;  ii,  edge  of  the  pock,  the  roof  at  this  point  con. 
ung  of  the  horny  and  transitional  layers.    X  25. 


340  INFLAMMATIOX. 

exudate  on  the  surface  of  a  mucous  membrane  or  external  wound,  so 
that  the  exudate  is  white  or  yellowish- white  in  color  and  of  a  milky  or 
creamy  consistence,  it  is  called  pus,  and  such  an  inflammation  is  desig- 
nated a  purulent  catarrh  (Fig.  205,  a).  A  persistent  marked  secretion 
is  termed  a  blnnwrrhwa.  Collections  of  pus  in  the  body-cavities — for 
example,  the  pericardial,  pleural,  or  joint  cavities^ — give  rise  to  purulent 
ejfimons  or  empyemata.  If  Mithin  a  blister  arising  through  the  lique- 
faction of  the  epithelial  lavers  beneath  the  horny  layer  of  the  epidermis 
there  takes  place  a  marked  collection  of  leucocytes,  the  fluid  becomes 
more  and  more  turbid,  white,  purulent,  and  the  vesicle  becomes  changed ' 
into  a  pustule  (Fig.  206,  /,). 

When  leucocytes  collect  in  such  large  numbers  within  a  tissue  as  to 


""Mm   ■ 


^m%^ 

1 

i 

^M-'/^ 

WM<M0^B0^^ 


Fig.  207.— Embolic  abscess  of  the  intestinal  wall  with  embolic  purulent  arteritis,  and  embolic  aneuris, 
in  cross-section  (alcohol,  fuchsin).  a,  b,  c,  d,  e.  Layers  of  intestinal  wall ;  f,  remains  of  arterial  wall,  crosi 
section;  f;,  embolus,  surrounded  by  pus-corpuscles  lying  within  the  dilated  and  partly  suppurating arter^ 
7i,  parietal  thrombus ;  i,  periarterial  purulent  inflltration  of  the  submucosa;  k,  vein  showing  marked  co' 
gestion.    X  28.  , 

give  it  a  white,  gray- white,  or  yellowish -white  color  the  process  assumi 
the  character  of  a  purulent  infiltration.  Should  this  be  followed  I 
li(iuefaetion  and  dissolution  of  the  tissue  the  process  results  finally  :; 
tissue=suppuration  and  abscess=formation  (Fig.  207,  i) — that  is,  intl; 
formation  of  a  cavity  filled  with  pus. 

When  purulent  infiltration  and  tissue-suppuration  occur  on  the  suj 
face  of  an  organ — for  example,  on  a  mucous  membrane  (Fig.  208,  d, 
fl) — the  process   leads    to   a    superficial   loss    of   substance — an  ulce 
The  formation,  through  suppuration,  of  duct-like  cavities  gives  rise  to  fi 
tulous  tracts. 

The  liquefaction  of  the  tissues,  which  is  designated  as  suppuratio' 


CAUSKS  OF  sri'i'i  jiA'iMox.  ;;41 

j  is  possible  only  under  the  condition  that  they  die.  This  tissue- necrosis  is 
j  usually  present  before  the  occurrence  of  sup])uration,  and  is  caused  by 
the  sp'ecitic  action  of  the  agent  exciting  the  inliamniation.  The  tissue 
I  may,  however,  die  only  during  the  course  of  inHanmiatory  infiltiation 
I  ami  (hen  li(|nefy. 

[        If  an  accnniulation  of  ])ns-corpuscles  is  associated  with  an  abundant 
'  collection  of  llnid,  the  exudate  is  si)oken  of  as  seropurulent ;  and  such 
an  exudate,  Avhen  intilt rating  t lie  tissues,  is  ott^'U   dcsignatrd   purulent 
,  oedema.     The  rapid  spread  of  a  purulent  or  ser(>i)urul('nt    inllannnatiou 
j  over  wide  areas — for  example,  through  extensive  areas  of  subcutaneous 
[or  submucosal  tissues — is  known  as  phlegmon   (Fig.  200,  r,  d).     Tins 
j  leads  very  often  to  the  formation  of  extensive  ])us-cavities,  iu  which 
there  lie  shreds  of  disintegrating  tissue  infiltrated  with  i)us. 
j        The  association  of  serous  exudation  and  fibrin  picripitation  with  snp- 
jpuration  leads  to  the  formation  of  fibrinopurulent  exudates  ( l*'ig.  LM).'), 
\d,  e);  and  effusions  into  the  body-ca\  ities,  and  meningeal  exudates,  as 
well  as  croupous  exudates  ou  mucous  surfaces  and  in  tlu^  lungs,  and  also 
phlegmons  may  bear  this  character.     It  is  to  be  noted,  however,  that 
with  the  increase  of  suppuration  the  formation  of  fibrin  becomes  de- 
creased, and  the  masses  of  coagula  already  present  dissohe.     Tlie  fibrin- 
masses  infiltrated  with  pus  are  white  and  easily  torn. 

Suppurations  and  the  associated  format  ion  of  abscesses  and  ulceis  are 
in  the  majority  of  cases  caused  by  bacteria,  most  frequently  by  the 
Staphylococcus  xnjogenes  aureus,  Strcpiococcus  pyogenes,  and  the  Gonococctis  ; 

/ 


Wr 


Fig.  208. -Suppuration  and  nt'cnsis  nf  thf  mucosa  of  the  laa'e  intestine  in  dysenU'ry  (MiilliT'.s  lluid, 
naBmatoxylin,  cosin).  Section  throusrti  the  miicosa  Ui\  ami  sutiuiucosa  (/))  of  the  larpe  intestine ;  <•.  inuswu- 
laris:  </,  interplandular,  (/,,  suhfrlandular  iiiHltration  of  the  mucosa;  c,  focus  of  inllllratlon  in  tlie  subinii- 
fosa;  /,  infiltrated  upper  (.'landular  layer  uuderfroiiiL'  desquamalion  ;  (/,  ulcer  with  inllltnited  base.     >;  ii. 

but  suppurations  due  to  Aef'ntomyces,  Baeillustiiplil  (tlxlomiiKiHs.  lUpIocoi-i'iis 
pneumou ifc,  <}]■  Wic  Ihtrfniion  eoli  eommutic,  nvv  not  rare.  The  ,sta|)li.\  lo 
icocci  generally  inodiice  localized  inllaimiiat ions;  streptococci,  on  llic 
other  hand,  i)hlegmonons.  The  i»rcscncc  of  <'ertaiii  bacteria  { lidcilhis 
'  lihlegmones  emphysematosfc,  Friinkel ;  Baeillus  aerogenen  eapsidoliis,  W«'lch) 
'inay  cause  the  formation  of  gas  (gos-p/ileginou).  Suppuration  is  some- 
jtimes  ectogenous,  sojnetimes  lymidiogenousor  luematogenous;  and  in  the 
jlast  case  often  bears  the  chai-acter  of  a  metastatic  process  (Fig.  207  j. 


342 


INFI^MMATION. 


Of  the  chemical  substances  which,  when  introduced  into  the  tissues, 
can  produce  suppuiatiuu  nuiy  be  mentioned  mercuiy,  oil  of  turpentine, 
petroleum,  Hxe-  to  ten-pei -cent,  solutions  of  silver  nitrate,  cieolin,  digi- 
toxin,  dilute  croton-oil,   and  sterilized 
cultures  of  various  bacteria,  in  which 
the   bacterial  proteins  are    the   active 
agents.       The    suppurations   produced 
by   chemical    substances    differ    from 
those    produced  by  infection,  in   that 
they  heal  more   easily,  do  not  spread 
in  the  tissues,  and  do  not  give  rise  to 
metastases,   and  through  the  fact  that 
theii'  i)r(»ducts  when  inoculated  possess 
no  virulence. 


«»^ 


j^^|: 


■  „.  .—  '^^'■■^^'if^':-'--ilvfyk 


^: 


Literature. 


{Suppuration  and  Gas-phJegmon.) 

Brandenburg:  Reaction  der  Leukocyten  auf 

Guajaktiuctur.       3Iunch.     ined.     Wocli., 

1900. 
Buchner:  Die  clieniisclie  Reizbaikeit  d.  Leii- 

Ivocvteii  u.  deren  Bezieli.  zur  Eiitztindung. 

Beil.    kliii.  AVocli.,     1890  ;    Bakterienpro- 

teini'  11.  (leien    Bezieh.    z.    Eatziiuduug. 

CI)!,  f.  V\x\v..  1S90. 
Bung-e:  Zur  Aeliologie    der   Gasplilegmonen. 

F'.rt^chr.  (1.   Med.,  xii.,  1894. 
Coenen:  Die     Aleiironat  -  Pleuritis.      Virch. 

Arch.,  163  Bd.,  1901. 
Councilman:  Zur    Aetiologie   der   Eiterung. 

Vireh.  Arch.,  92  Bd.,   1883. 
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Zellen  d.   Eiters.     V.   A.,   173   Bd.,  'l903 

(Lit.). 
Dmochowski  u.  Janowski:  Eiterung  erreg. 

AVirk.  d.  T.vpliusl)aci]lu.s.     Beitr.  v.  Ziee- 

ler,  xvii.,  IS'.).-)  (Lit.). 
Dubler:  Ein   Bcitrau'  zur  Lelire  von  der  Ei- 
terung. BaseL  1890. 
Fraenkei,    C:   Ueber     die 

Leipzig,     1893;     Muncl 

1899     " 


Fig.  ^09.— PhlepiiK.n  of  the 
sue  with  formation  of  a  visiCl 
(Muller'sfluid,  hspiiiiitoxylin,! 
b,  epidermis;  c,  iiitlliratt-d  f:i 
of  pus  ;  e,  cellular  foel  in  oorium  ;  /,  subepit  I 
lial  vesicle  due  to  oedema.    X  3H.  -, 


uibcutaneous  1  j 
tlirough  oedeii 
)sin).  a,  Coriirj 
tissue;  <?,  fo(; 


Gasplilegmonen, 

med.      Woch., 

Z.  f.  Ilyg.,  40  Bd.,  1902;  Gaspldeg- 

nione  u.  Schaumorgane.    Ergebn.  d.  a.  P., 

vii.,  1904.  ; 

Grawitz:   Bedeutung  des  Cadaverins  flir  d.  Entstehen  von  Eiterung.     Virch.  Arc!, 

110  Bd.,   1887;   Zur  Theorie  der  Eiterung.     lb.,  116  Bd  ;  Histol.  Verilnd.  bei  «|.' 

eiteriireu  Entziiuduug.     lb.,  118  Bd.,  1889.  i 

V.  Hibler:  Spaltpiize  in  Zellen  bei  Eiterung.     Cbl.  f.  Bakt.,  xix.,  1896.  j 

Janowski:    Die  Ursachen  der  Eiterung.     Beitr.  v.  Ziegler,  xv.,  1894  (Lit.);  Morplj;- 

o-ie  des  Eiters.     Arch.  f.  exp,  Path.,  36  Bd.,  1895.  ' 

Kaufmann:  Einflnss  des  Digitoxins  auf  die  Entstehung  eiteriger  Phlegmonen.     Arj. 

f.  exp.  Path.,  XXV.,  1889;  Die  Entstehung  der  Entzlinduug,  Leipzig,  1891.  j 
Kiener  et  Duclert:  Formation  at  guerison  des  absces.  Arch,  de  med.  exp.,  v.,  ISEi 
Klempner:  Ueb.  d.  Bez.  d.  Mikroorganismen  z.  Eiterung.     Zeitschr.  f.  klin.  Med.,  ', 

issn.  ; 

Kronacher:   Die  Aetiologie  und  das  Weseu  der  acuten  eiterlgen  Entztiudung,  Je ', 

IS'.n,  : 

Krynski:   Ueber  die  Ursachen  acut-eiteriger  Entziindungen.     CbL  f.  allg.  Path,  .i 

1890. 
Lemiere.  Dt 


la  sujipuration,  Paris,  1892. 


NECROTIC    IXFLAMMATIOX.  343 

Levy;  Die  mikrooruaiiisiiu'ii  der  Eitrning.     Aicli.  f.  exp.  Piilli.,  2J)  Bd.,  1891. 
Miiller:  Stand  diT  Eitrruiigst'niiji'.     ("1)1.  f.  IJakt.,  xv.,  18!»4. 

Muscatello:  Kliol.  dclla  caiKrcna  (.'iiilisfmalica.     Aicli.  per  Ic  Sc.  Med.,  xx.,  189(5. 
Nathan:  Ziir  Artiologie  diT  EitiMUiiir.      Langciihcck's  Arcli.,  xxxvii,,  iWs.  ' 
Orthmann:  I'i'Irt  die  Ursaclicu  der  Eitcihildung.     Virch.  Arch.,  !«)  IJd..  1SS2. 
Passet;   rntfisuchungcu  iib.  d.  Aetiologk- d.  lairrig.  Plilfginoiie  d.  3Iouscheu,  Ik'rlin 

iss.j. 
Peiper:  Eiterige  Schmelzung  dcr  Gewebo.     Viirli.  Arcli.,  llSBd.,  1889. 
Rinne:  IKt  Eiterungsprocess  und  sciue  ^letastasi'ii,  Ikrliii,  1889. 
Roger:  Do  la  suppuiatlou.     Kevue  de  Chir.,  1891. 
Sandler:  (itisphk'gmone  u.  Scliaiimorgane.     C.  f.  a.  P.,  xiii..  1902. 
Steinhaus:  Die  Ai'tiologio  dcr  aciitcn  Eitcrunii-.  Lcip/i^'.  1880. 
Stolz:  (;a>phlroni(iiie.    "B.  v.  Bniiis,  xxxiii..  1!M)2. 
Welch  ami  Nuttall:  Gas  Plilogiiion.     J.  Hopkins.  Bull.,  lS!t2. 

See  also  j-^  8!»-91. 

^93.  As  was  explained  iu  §  9l',  siippuiati\  e  iullanimatioii  always 
leads  to  tissue- necrosis;  but  this  necrosis  is  immediately  lost  sifjht  of  in  tiie 
presence  of  the  licpiefaction  and  dissolution  of  the  tis.sues  Mhich  foriu 
the  characteristic  feature  of  suppuration.  In  other  forms  of  action  upon 
the  tissues,  there  may  occur  a  more  extensive  tissue -uecrosis,  recoguiz- 


%b 


flf        ^11         *f.  1^       I         ^ 

Fig.  210.— Necrosis  of  the  epithelium  of  the  epiglottis  (MiiUer's  fluid.  ha°matoxylin).  «,  Living  epl- 
tbelium  with  well-staiued  nuclei;  b,  necrotic  epithelium  with  nuclei  nut  staining?  ;  t,  leucoo.vte.s  lyiuK  hi 
the  epithelium ;  </,  hypera?mic,  inflamed,  and  infiltrated  connective  tissue.    X  300. 

able  even  to  the  unaided  eye,  which  is  not  followed  l)y  suj^puration,  but 

ou  the  other  hand  is  characterized  by  the  fact  that  the  necrotic  portions 

of  the  tissue  remain  unchanged  for  a  long  time,  and  only  relatively  la1«' 

I  are  removed  through  sequestration  and  sloughing  or  through  absorption. 

,  Since  the  tissue-necrosis  in  such  a  case  lornis  tlic  chief  fcatnic,  the  con- 

j  (litiou  may  be  appropriately  designated  a  necrotic  inflammation. 

The  tissue- necrosis  associated  with  iiillanuiial  ion  may  lie  (•aus<'(l  by 
•  caustic  chemicals,  high  or  low  temperatures,  and  ischa;mia,  as  well  as 
I  by  infection  (typhoid  fever,  diphtheria,  dysentery,  and  tubcrcnlosis). 
I  The  necrosis  of  the  tissue  may  appear  hrst  of  all  as  the  immediat*' 
'  effect  of  the  injurious  action,  the  inliammatory  exudation  fullowing 
I  later,  and  being  confined  to  the  region  adjoining  the  necrosis;  tiiis  is 
'  e.specially  the  case  after  the  action  of  corrosive  substances,  and  higli 
^  temperatiii-e,  and  in  ischtemia.  In  other  cases,  which  belong  cliielly  t(» 
the  iiifeet ions,  an  inflammation  is  first  establislied,  tlie  inllaiued  and  in- 
I  filtrated  tissue  later  becoming  necrosed.  In  tuberculous  iid'eclinns  th»' 
'  necrosis  occurs  only  after  the  tissue-proliferatiou  has  develoi)ed  and  has 
;  existed  for  some  time. 


344 


INFLAMMATIOX. 


^-^^ 


Necrotic  inflammations  are  most  frequently  seen  on  the  mucous  mem 
braues,  and  are  here  usually  called  diphtheritis,  particularly  those  whicL 
are  caused  by  infection.     The  necrosis  may  at  lirst  affect  the  epithelium, 
which  iu  consequence   loses 
its  nuclei  (Fig.  210,  b)  and 
later  accjuires  a  lumpy  ap- 
joearance.       If     there     are 
formed   m-  h  i  t  e,    o  p  a  q  u  e 
patches    ujiou    the    mucous 
membrane,  as   in  the  phar- 
ynx iu  diphtheria,  the  con- 
dition may  be  spoken  of  as 
epithelial  or  superficial   dipli 
f/ieritis.      Usually,   however, 
the  designation  diphtheritis  is 
applied  only   to    tissue   ne- 
croses in  which  the  inflamed 
and  infiltrated  con  n  ective 
tissue    iindergoes    necrosis 
(Fig.  211,  «),   and  becomes 
converted  into  a  lumpy  or 
granular   mass  without  nu 
clei,   or  into  a  more  homo 
geneous     mass      containing 
fibrin,  in  which  the  struct- 
ure   of    the  tissue   can    no 
longer  be  recognized. 

Diphtheritic      sloughing 
of  the  tissues  of   a  mucous 
membrane  is  observed  par- 
ticularly often  in  the  intestine   (Fig.  211),   but   occurs  also    in    othe 
mucous  membranes,  as  in  those  of  the  vagina,    the  descending  urinar 
passages,  and  the  region  of  the  throat,  where  the  tonsils  are  especiall 

frequently  affeci 
ed,  etc.  The  m: 
erotic  tissue  forn:| 
i^^fr-'^  ff"~t^>%  white,  or  grayisli 
white,  or,  through 
the  admixtni-e  (' 
blood  or  bile  <' 
other  impuritie; 
dark  green,  yelloA^! 
brown,  or  othe;; 
wise  c  o  1  o  1*  e 
sloughs,  which  nh 
surrounded  byrec 
dened  and  inflamcj 
tissue.  If  somi 
time  has  alread: 
elapsed  since  i; 
formation,  and  if 
liquefaction  of  tl 
tissue  at  the  boun( 
ary    between  th 


1 


Fig.  211.— Bacillary  diphtheritis  of  the  large  intestine  ;■ 
dysentery  (alcohol,  gentian  violet).  «,  Necrotic  portion  >' 
the  glandular  layer  of  the  mucosa,  infiltrated  with  bacilli;  il 
intact  intlaiiied  mucosa;  i\  muscularis  mucosae;  d,  su. 
mucosa;  - .  coionli's  of  bacilli;  /,  glands  with  living  epithj 
Hum ;  (/,  glands  with  necrotic  epithelium  and  bacilli ;  h,  co  < 
nective  tissue  iuBltrated  with  cells  ;  (",  blood-vessels.    ;■-  SO.  I 


,^^ 


x^i 


¥ 


Fig  212.-  Section  of  the  uvula  in  pharyngeal  diphtheria  with  croupous 
deposits  (alcohol,  aniline  brown),  o.  Normal  epithelium;  ?),  connective 
tissue  of  the  mucous  membrane ;  c,  reticulated  fibrin ;  (I  connective  tissue 
of  mucosa  mflltrated  with  coagulated  flbrin  and  round  cells,  and  partly 
necrotic ;  e,  blood-vessels ;  /,  haemorrhage ;  g,  clumps  of  micrococci.    X  75. 


iip:altxg  of  acute  ixflamma  riox. 

iving  and  dead  ti.ssues  has  occurred,  with  a  sepaiatioii 
be  necrosed  parts  t'oini  h)OselY  attaclied  oi-  wliolly  i're«' 
)a  the   surface    of  tlie    membrane,    these   consist in.u'  at 

small  Hakes,  at  otJier  l 


Fio.  213.— Diphtheritic  necrosis  within  a 
wollen  mesenteric  lymph-Kland,  in  typlioid 
ipver  (alcoliol.  flbrin-stain).  Fibrin  network 
:<'tween  the  necrotic  cells.    X  300. 


characterized 


345 

(.f  the  hitter. 
(h'])(»sits  iyiu}:: 
times  only  of 
times  of  lar<;er 
sUm<;hs. 

I  )il)ht]ieritisof  mucous  mem])ranes 
may  be  associated  with  croupous  (h'- 
l)osits  (Fij;-.  212,  e,  d),  so  tliat  the 
tissue-necrosis  (d)  may  be  covered 
over  Avilli  iil)rin  (r). 

WouiHl-^ranulations  may  also  ne- 
crose in  the  same  way  as  do  intlamed 
mucous  membianes;  sucii  a  condi- 
tion may  therefor*^  ))e  called  iround- 
dipldhcritis. 

Acute  tissue- necroses  caused  by 
infection  occur  in  the  case  of  the 
internal  organs,  chietiy  in  tlie  lympli- 
glands  (Fig.  213),  spleen  and  bone- 
by  the  formation  of  o])a(iue  grayisli 


marrow,    and  are 

vhite,    yellowish,    or   dirty-gray   sloughs.     Xot-   infrequently   librinous 

•xudations  are  seen  within  the  necrotic  tissue  (Figs.  212,  d  :  213). 

,     In  the  necrosis  caused  by  tuberculosis  the  destruction  of  the  tissue 

kcurs  gradually,  and  bears  the  character  of  a  caseation. 

(     When  an  intiammatory  focus  contains  bacteria  which  excite  puti-id 

leconii)ositi()n  of  albuminoid  liodies,  the  inflammation  may  take  on  the 

;haracter  of  a  putrid  gangrene  ;  and  the  tissue  may  disintegrate  into  a 

lirty  gray  or  black,  tinder-like  mass  which  gradually  dissolves  and  gives 

•If  an  extremely  disagreeable  odor.     Gas-bubbles  are   also  sometimes 

(leveloped  in  the  focus.     (See  ^  92.) 


Literature. 

(Xerrotic  Injlam  mat  ion . ) 

pomil:  Anat.  patliol.  des  ulcerations  iiilcst.  dans  la  dv.senteric.     Arcli.   dcpljys. ,   v., 

I       1SS3 

Hoffmann:  Unters.  ul)cr.   d.  pathol.-anat.  Ycrand.  dcr  Orgauc  Ix'i  Abdnminaltyplms, 

ISC,!). 
/.  Kahlden:    Die  Actiologic  u.  Geuese  der  aciiten  Xepliritis.     Ik'ilr.  v.  Ziogli-r,   .\i., 

Kaufmann:  Die  Sublimatvergiftung.  Breslaii,  1S88.     Virch.  Arcli.,  117  IM..  1SS9. 
Kelsch:  Contrib.  a  I'anat.  patliol.  de  la  dysenteric.     Arch,  de  phys.,  v..  ISTo. 
Lesser;    Die  anat.  Verand.  d.   Verdauungskanalcs  durcli  Aetzgifte.     N'ircii.  Arch.,  S:j 

H(i.,  ISSI. 
Letulle  el  Vaquez:   Einpoisonnement  par  I'acide  chlorhydriciuc.     Arch,  de  piiys.,  i., 

iss!). 
Marchand:    Darniveranderuugeii   bei  Typhus  abdominalis.      C'l)l.    f.    allg.   J'ath..  i., 

Is'.IO. 
Matzenauer:  Ilospitalbrand.     Arch.  f.  Derm.,  55  lid.,  1901. 
Neuberger:  Wirkung  des  Sublimats  auf  die  Nieren.     Beitr.  v.  Zieglcr,  vi.,  18S«). 
.      See  also  i-^  89-92 


II.  The  Termination  of  Acute  Inflammation  in   Healing. 

§  94.  Should  there  occur  in  any  tissue  what.soe\er  an  acute  inlhniima- 
tion,  sooner  or  later  there  always  arise  processes  which  ha\c  in  aim  \\w 


346  IXFLAMMATIOX. 


removal  of  the  chauges  established  and  a  restoration  of  the  degenerate 
tissue,  and  which  may  therefore  be  regarded  as  processes  of  repair.  ] 
the  cause  which  excited  the  inflammation  is  no  longer  present,  thes 
processes  consist  essentially  in  the  cessation  of  the  jMitholof/ical  exudatio 
and  its  replacement  by  the  normal  vascular  secretion,  the  removal  or  ahsorj 
Hon  of  the  exudate  present  and  of  the  necrotic  tissue,  and  the  restoration  ofth 
destroyed  tissue.  If  the  exciting  cause  of  the  inflammation  is  still  present  i| 
the  tissue  and  active,  it  must  1>e  removed  or  rendered  inert. 

The  cessation  of  the  alteration  of  the  vessel= walls  is  brouglit  aboi 
through  the  restoration  of  the  normal  blood-suj^ply  to  the  damaged  blooG 
vessels,  so  that  the  nutrition  of  the  vessels  again  becomes  normal.  If  tl 
alteration  was  slight,  and  if  the  exciting  cause  of  the  inflammation  ha 
acted  only  for  a  short  time — if  it  is  the  case,  for  example,  only  of  tli 
brief  action  of  a  trauma,  or  high  temperature,  or  chemical  substance,  th;: 
was  quickly  removed — the  restoration  of  the  vessels  may  take  place  in  ■ 
very  short  time,  i.e. ,  in  a  time  that  may  be  measured  in  minutes  and  hour; 

When  the  exciting  cause  of  the  inflammation  acts  for  some  length  c 
time — as,  for  example,  in  the  case  of  bacteria  which  live  and  multiply  ij 
the  tissues,  or  if  changes  are  brought  about  through  the  inflamniatic 
itself,  which  act  in  such  a  manner  as  to  alter  the  vessels — if  there  hj 
been,  for  exami^le,  a  tissue-necrosis — the  vessels  are  subjected  for  sonl 
time  to  a  continued  harmful  action,  which  hinders  the  complete  restor' 
tion  of  their  functions.  \ 


Fig.  214.— Phagocytes  from  granulation  tissue  with  included  leucocytes  and  fragments  of  same  (f!- 
limate,  Biondi's  stain),  o.  Round,  h,  spindle,  fibroblast  with  leucocytes ;  c,  ((,  e,  fibroblasts  containingi- 
mains  of  leucocytes.     :■:  500.  ] 

The  absorption  of  the  exudate  occurs  in  many  cases  easily  a,l 
quickly,  in  that  it  is  taken  up  by  the  lymph-stream,  eventually  also  ^ 
the  blood.  This  takes  place  most  quickly  in  the  case  of  serous  exudat;, 
yet  in  many  places  fibrinous  exudates  may  also  be  quite  rapidly  removt', 
but  this  occurs  only  when  the  coagula  soon  liquefy.  For  example,  1|e 
coagulated  exudate  in  the  lung  may  be  liquefied  and  made  capable  f 
absorption  through  the  action  of  'A proteolytic  enzyme  (Miiller)  that  aris 
most  probably  from  the  leucocytes.  The  absorption  of  exudates  is  v<y 
often  aided  by  phagocytes,  that  is,  through  the  activity  of  ama^boid  ct'S 
present  in  the  inflamed  area,  in  taking  \\\)  corpuscular  substances  ad 
destroying  them.  Thus,  for  example,  large  mononuclear  cells  (mac,- 
phages)  lying  within  the  inflamed  area  may  take  up  through  au:?- 
boid  movement  polynuclear  leucocytes  (Fig.  214,  a,  h)  and  destroy  fid 
digest  them  (c,  d,  e).  In  the  same  manner  red  blood-cells  and  tbr 
disintegration-i)roducts  may  be  taken  up  (Fig.  115 ).  Firmer  fibrin*  S 
exudates  such  as  are  formed  especially  upon  the  serous  membranes,  fd 
also  large  collections  of  pus,  usually  offer  considerable  resistance  to  >- 
sorption  and  are  the  cause  of  the  prolonged  course  of  the  inflammatii, 
although  the  character  of  this  may  become  changed  from  what  it  waf  n 


IlEALIXG    OF    ACUTP:    IM  LAM  M  A  IK  )\.  .S47 

he  beginning-.  In  very  many  cases  ahsorj)! ion  is  acconiiilished  by  the 
;iniultaneons  snbstitntion  for  the  exudate  of  (Miibryonic  lissiu*  which 
ater  bcconu's  ehanged  into  coiHicctixc  tissue. 

Tile  sequestration  and  absorption  of  necrosed  tissue,  with  tiie  e\- 
•eption  of  tlie  easliiig-off  of  dead  epitlieliuni,  wliich  may  l»e  veiy  (|uielJy 
iccomplished,  always  require  a  certain  leiigtii  of  time,  whieli  varies 
u'COidiug  to  tlie  nature,  situatiou,  and  extent  of  the  necrosed  tissue, 
[n  general,  the  inllannnation  persists  as  long  as  neei-otic  tissue  is  still  ])res- 
■nt.  Suprrjicial  necrosed  iis-wrsma!/  be  cast  off  after  seiiHcstration^ihwi  is, 
ifter  the  separation  of  the  dead  from  the  living  tissues.  lu  the  case  of 
ileep-seated  tissue-necroses  in  Avhicli  the  tissue  does  not  soon  undergo 
jotal  liciuefaction,  al>.sorj)tio)i  is  usually  slow,  and  is  brought  altout  llnougli 
ji  gradual  substitution  of  living  tissu(^  for  the  dead.  F^hagocytosis  often 
fakes  i)laoe  also  in  the  absorption  of  necrotic  tissue.  Falty  ]>riiduets  of 
[.lisintegration,  which  have  a  positive  chemotactic  action  uj)ou  tiie  anue- 
|i)oid  cells,  are  taken  up  in  large  amounts,  so  ihut  fat -f/ratiidc  .sfj/ie rules  are 
jformed  (see  Fig.  0!>). 

t  The  regeneration  of  the  degenerated  tissue  is  dependent,  for  its  oc- 
currence, partly  upon  the  degree  and  extent  of  the  degeneration,  partly 
i.ipou  the  nature  of  the  tissue,  and  partly  upon  the  mode  of  action  of  the 
jigent  exciting  the  inHamnmtion. 

1  If  the  tissue-cells  of  the  intlamed  area  are  but  slightly  degenerated, 
they  are  quickly  restored  when  the  nutrition  becomes  normal.  If  single 
pells  are  lost  but  the  organization  of  the  whole  is  not  disturbed,  there  can 
[take  place  in  most  tissues  a  rapid  renewal  of  cells  through  a  regenerati\e 
ijrowth  of  the  remaining  cells.  This  is  true  particnlai'ly  of  tlu^  diifereut 
forms  of  connective  tissue,  the  surface  epithelium,  liver-  and  kidney-cells, 
while  ganglion-cells,  bone-cells,  cartilage-cells,  and  heart-muscie  cells 
possess  but  little  or  no  power  of  regeneration  (see  Chapter  YI.).  Ex- 
tensive destruction  of  tissue  with  solutions  of  continuity,  wounds,  fi-ac- 
jtures,  suppurations,  necrotic  inllammations,  etc.,  lead  to  tissue-i)iolifer- 
•ations,  which  are  indeed  sufficient  to  close  the  defect,  but  for  the  greater 
•part  do  not  lead  to  a  restoration  of  the  normal  tissue,  but  to  the  foi-ma- 
jtiou  of  a  tissue  of  a  lower  grade,  which  in  its  earliest  stages  is  known  as 
granulation  tissue,  in  its  mature  form  as  cicatricial  tissue. 

With  the  entrance  of  regenerative  proliferation  and  the  formation  of 
granulation  tissue,  there  appears  in  the  course  of  the  intlamniatiou  a 
Iphenonienou  which  lat<'r  gives  to  the  inllammatiou  an  es|)e('ial  charac- 
Iter,  so  that  it  may  l)e  designated  a  proliferating  inflammation. 
I  The  phenomena  of  proliferation  begin  in  iuthimed  tissues,  at  the 
jearlies.  after  eight  hours,  but  unt  usually  first  clearly  recognizable  after 
Ifroni  twenty-four  to  forty-eight  hours. 

i  In  general,  they  appear  the  more  rapidly  the  milder  the  inllamma- 
ftion  and  the  moie  quickly  the  pathological  exudation  is  oNcreonn'  (»r 
!<liininished.  Wui)puration,  necrosis,  and  gangrene  of  the  tissues  hinder 
Iproliferaiiim  and  retard  the  beginning  of  rei)air,  oral  h'ast  contine  the 
(reparative  processes  to  the  neighljoring  tissues. 

i  Every  tissue  capable  of  proliferation  furnishes  formative  cells  for 
(tissue  of  its  own  kind  or  for  one  closely  related  to  it.  Pus-coipuscles  are 
liiot  formed  by  the  tissue-cells;  on  the  other  hand,  cells  neir/i/  ilereloped 
\from  the  tissue-cells  by  proliferation  way  become  mixed  with  the  exudate, 
^degenerate  in  the  same,  and  die.  Thus  iiot  all  the  cells  newly  developed 
|through  proliferation  fulfil  their  function  of  i»ro(lucing  new  tissue. 
j      The  removal  of  the  exciting  cause  of  inflammation  takes  i)lace  very 


348  INFLAMMATION. 


differently  in  different  cases,  and  depends  in  tlie  first  place  upon  th 
natnre  of  the  cause.  Many  trauniatisnis  and  thermal  intluences  act  b 
for  a  short  time,  and  have  no  further  influence  upon  the  course  of  th 
inflammation.  3Iany  substances  acting  chemically  may  be  quickly  take, 
up  bj^the  tissue-juices  and  made  inert,  or  excreted,  while  others  remai 
locally  active  for  a  longer  time.  InsoiuhJe  foreign  bodies  in  the  form  of  du^ 
which  have  penetrated  into  the  tissue,  as,  for  example,  into  the  lungi-j 
are  for  the  greater  part  taken  np  hy  phayoeytes  and  carried  away  (se 
§  21)  and  either  deposited  here  or  there,  or  are  removed  from  the  l»od^ 
Of  the  bactei-ia  exciting  inflammation,  many  soon  die  as  the  result  c 
baeterieid(d  sub,sfanees  formed  in  the  diseased  area  (see  §  311.  Thedestnn 
Hon  of  the  bacteria  tal'es  plaee  partly  in  the  tissne-fuids  and  partly  b 
phagocytosis,  the  bacteria  being  taken  up  by  the  cells  either  alive  or  ha\| 
ing  first  been  killed  are  then  digested.  Of  the  bacteria  xn-oducii]! 
inflammation,  many  soon  die,  while  others  live  and  constantly  prt 
duce  new  generations  which  in  turn  cause  new  inflammation,  often  i 
such  a  way  that  in  the  first  diseased  focus  the  inflammation  may  subsicj 
and  healing  take  place,  while  in  the  neighborhood,  or  even  in  more  dii 
tant  regions,  metast<dic  -inf  animations  develop.  { 

On  account  of  the  gieat  differences  which  exist  both  in  the  nature arj 
the  behavior  of  the  exciting  cause  of  the  inflammation,  as  well  as  in  tlj 
course  of  the  inflammatory  tissue-degeneration  and  the  exudation,  and  :* 
the  course  of  the  healing  processes,  it  is  easy  to  understand  that  the  who- 
course  of  an  inflammation,  even  to  its  termination  in  healing,  may  vail 
greatly  in  ditfereut  cases,  so  that  all  the  possibilities  of  its  course  Cj 
hardly  be  reviewed.  At  the  same  time  it  is  not  difficult  to  compreheij 
the  decline  of  the  different  forms  of  inflammation,  since  ultimately  tli 
whole  process  is  always  made  up  of  the  same  factors — that  is,  of  tissui 
degeneration,  pathological  exudation,  and  of  jjrol iterative  processes,  tlj 
last  of  which  are  calculated  to  remove  the  disturbances  caused  by  t:| 
first  two  factors.  , 

Neumann  groups  under  the  term  inflammation  all  those  phenomena  which  devel , 
locally  after  a  primary  tissue-lesion,  and  are  directed  toward  the  healinsj  of  this  lesic| 
According  to  this  view,  regeneration  is,  therefore,  the  most  important  part  of  the  ij 
flammatory  process,  in  that  it  is  especially  adapted  to  restore  the  defect  of  tissue  causj 
by  the  primary  tissue-lesion,  or,  as  Neumann  puts  it,  to  restore  the  uninterrupted  ccj 
tinuity  of  the  tissue.  Such  an  identification  of  inflammation  with  regeneration  I  hcj 
as  inadmissible,  in  the  first  place  because  tissue-regenerations  occur  which  clinical 
and  anatomically  in  no  way  bear  the  character  of  an  inflammatory  process.  Then  a  I 
the  inflammatory  pathological  exudations  cannot  be  regarded  as  phenomena  that  cl 
be  compared  with  regeneration,  and  that,  like  it,  have  for  an  end  the  healing  of  \\ 
primary  tissue- lesion.  Even  if  they  act  favorably  in  individual  cases  (the  productij. 
of  bactericidal  antibodies,  formation  of  complement  by  leucocytes),  this  is  not  alwap 
true.  Much  more  often  do  they  cause  serious  damage  which  increases  that  establisll 
by  the  primary'  tissue-lesion,  and  often  enough  form  a  hindrance  to  the  rapid  establi  r 
ment  of  the  healing  process.  ; 

The  phenomena  of  chemotropismus  or  chemotaxis,  that  is,  the  attraction 'r 
repulsion  of  motile  cells  by  chemical  sulistances  sohilile  in  water,  were  first  observed/ 
Struhl  and  P/V^er,  who  carried  out  observations  on  the  myxomycetes,  infusoria,  b- 
teria,  s])ermatozoa,  and  zoospores.  Investigations  by  Leber,  Massarf,  Bordct,  Borissn, 
GahntHchewsky,  and  others  have  shown  that  the  leucocytes  likewise  are  attracted  ;'' 
chemical  substances  {positive  chemotropismus  or  chemotaxis)  or  are  repelled  by  th^i 
(negative  chemotropismus).  In  particular  do  products  of  the  vital  activities  of  f 
fission-fungi  (Leber,  Massart,  Bordet,  Gabritscheu'sky),  or  the  bacterial  proteins,  that», 
alliuminous  bodies  of  the  dead  bacterial  cells  (Buchner),  even  in  a  great  dilution  (accQi- 
ing  to  Buchner,  pyocyaneus  protein  acts  even  in  a  three-hundred-fold  dilution),  possjs 
a  positive  chemotactic  action.  According  to  Buchner,  this  property  is  shown  also  f 
gluten-casein  from  wheat-gluten  and  legumin,  aleuronate,  glue  from  bones,  and  alhi 


1 

th(fl 

bufl 


PHAGOCYTOSIS    AM)    (1 1  i:.M(  )IA  \  IS.  349 

;ilbuminates  from  peas,  while  ammoniuin  butyrato.  tritiK'tliylaiiiiii,  aminonia,  leuciii, 
tyrosin,  urea,  and  skatol  show  negative  chcniotaxis. 

Literature. 

(Fhar/oc[f(o.si.s  and   ClKntoUixis.) 

Arnold:  Staubinhalation  u.  Staiibmetastase,  Leipzig,  ISSo;    Ueber  die  Geschicke   dor 

Leukocyten  in  der  FremdkorpereniboHe.     Virch.  Arch..  V.Vi  Bd..  1893. 
Barfurtli:   Die  Riicklnldung  des  Froschkrvenschwanzes.     Ar<?h.  f.  mikr.  Anat.,  xxix., 

lS,s7. 
Bloch:  (.'heinotaxis.     Cbl.  f.  allg.  Path.,  vii.,  1S96. 

Borissow:  Cheiuotakt.  Wirkung  versch.  Substanzen.     Beitr.  v.  Ziegler,  xv.,  1S94. 
Bordet;    Phagocyto.se.     Ann.  de  llnst.  Pasteur,  x.,  1890. 
Buchner:   Die   cheinische   Reizbarkeit   der   Leukocyten    untl    deren    Beziehinig   zur 

Entziuidung.     Muncli.  med.  Woch.,  1890,  u.  Berl.  kUii.  Woch..  1890.  ref.  ("1)1.  f. 

Bakt..  ix.,  1891;    Pyogene  8toffe  in  d.  Bakterienzellen.     Berl.  klin.  Woch.,  1890; 

Die   Ent  .vickelung  der  Bakterienforschung  seit   Xiigelis   Eingreifen   in   ilieselbe. 

Miinch.  med.  Woch.,  1891. 
iCantacuzene:  Mode  de  resorpt.  des  cell,  h^patiques.     A.  d.  IT.  P.,  1902. 
Cassaet:   De  I'absorption  des  corps  solides.     Arch,  de  med.  exp.,  iv.,  1892. 
Dineur:  Sensibilite  des  leucocytes  a  I'electricite.     Soc.  des  sciences  m^d.  de  Bruxelies, 

1892. 
Fleiner:   Resorption  korpuskularer  Elemente  durch  Lunge  u.  Pleura.     V.  A.,  112  Bd., 

1S8S. 
Gabritschewsky :   Proprietes  chimiotactiques  des  leucocytes.    Ann.  de  .'Tnst.  Pasteur, 
!         iv..    1890. 

|Heidenh.aiii:  Hi.stologie  u.  Physiologic  tl.  DiiDndarmschlciniliaut.     Pflusrcrs  .\rch.,  48 
I         Bd..  1888. 

V.  Kolliker;  Die  normale  Resorption  des  Knochengewebes.     Leipzig,  1887. 
Knickmann:    Ercnidkorpertuberkulo.se.     Virch.  Arch..  138  Bd.,  Suppl.,  1894. 
Langhans:    Bcul)achtungen  iiber  Resorption  der  Extra vasate.  Virch.  Arch.,  49  Bd., 

1870. 
Lesser:  Ueber  das  Verhalten  des  Catgut  im  Organismus.     Virch.  Arch.,  95  Bd.,  1884. 
Loos:   Degenerationserscheinungen  im  Tierreiche.  bes.  iiber  die  Reduktion  des  Frosch- 

larven-schwanzes.  Leipzig.  1889;    ref.  Biol.  Cbl.,  ix. 
Lebert:   Die   Entstehung  der  Entziindung,  Leipzig,  1891,  u.  Fortschr.  d.  Med.,  vii., 

isss. 
Massart  (  i  Bordet:   Rech.  sur  I'irritabilite  des  leucocytes,  Bruxelies,  1890. 
Massartci  Rodet:    Le  chimiotaxisme  des  leucocytes  et  I'infection.     Ann.  de  I'lnst. 

Pa.st..  v..    1.S91. 
(Metschnikoflf:   Intracellulare  Verdauung,  Wien.  1883.  u.   Biol.  Cbl..  ii.,  1883;    Path- 
I        ologie  comparee  de  I'lnflammation,  Paris.  1892;  La  phagocytose  niu.sculaire.    Ann. 
I        de  ITnst.  Pasteur,  vi..  1892;    La  resorption  des  cellules.    Jb..  1899;  Phagocytose. 
!         Handl).  d.  pathog.  Mikroorg.,  iv.,  1904. 

iMuscatello:   Aufsaugungsvermogen  des  Pcritoneums.     \'.  A..  142  Bd.,  189."). 
Nikiforoff:   Bau  und  Entwickelung  des  Granulation-sgewebes.     Beitr.  v.  Zicglcr,  viii., 

\S\)[). 

Noetzel:   Histolyse.     Virch.  Arch..  151  Bd.,  1898. 

Pfeflfer:    I'cber  chemotakti.sche     Bewcgungen    von    Bakterien,   Flagellatcn    u.  Vol- 

vccincen.     Unters.  a.  d.  botan.  Inst,  zu  Tubingen,  ii.,  1888. 
Ponfick:    Studien  iib.  d.  Schicksale  korniger  Farbstoffe  im  Organismus.     ^".  A.,  48 

Hd..   1S(;9. 
Rindfleisch:  Experimentalstudien  iiber  die  Histologie  des  Blutes,  1863. 
Roser,  K.:   Beitrage  zur  Biologic  nicdcrster  Organismen.  Marburg.  1891. 
Ruppert:   Exper.  Unters.  iib.  Kohlciislaubinhalation.     Virch.  Arch.,  72  Bd.,  1878, 
Slavjansky:  Exper.  Beitr.  z.  Pncunionokoniosislehrc.     Virch.  Arch..  48  Bd.,  1869. 
Werigo:   La  chimiotaxie  negative.     A.  de  med.  exp..  1901. 
iWoronin:  Chomotaxis  u.  taktile  Empfindlichkeit  d.  Leukocyten.     (1)1.  f.  H.ikt..  xvi., 

1894. 
Ziegler:   Exper.  I'nters.  iiber  die  Herkunft  der  Tuberkelelenicntc.  Wiirzl)urf.',  1875; 

I'nters.  iiber  pathologische  Bindegewebes-  und  Gefassneubildung,  Wiirzburg,  1876. 

Seealso  §§  95  and  97. 


350 


INFLAMMATION. 


III.  Inflammatory  New=formation  of  Tissue  ;  Healing  of  Wounds  an 
Substitution  of  Exudates  and  Tissue=necroses  by  Connectiv 
Tissue, 

§  95.  The  inflammatory  proliferation  of  tissue  isesseutially  a  iegei| 
erative  process  which  aims  to  couipeiisate  for  the  tissue-lesion  produeei 
by  any  cause  of  iullammatioii.  Especial  conditions  may  so  intineu(' 
the  process  that  they  not  rarely  lead  to  hyi)erplastic  proliferations  of  tl 
connective  tissue  which  fail  to  accomplish  this  purpose  and  cause  nei 
injury,  and  this  is  especially  the  case  when  the  cause  of  inflammatic! 
(chronic  infection)  or  the  persistence  of  the  residues  of  acute  infl.amm;| 
tiou  (exudates,  abscesses,  tissue  necroses)  keep  up  a  chronic  conditi(| 
of  inflammation.  ' 

The  inflammatory  new-formation  of  tissue  is  brought  about  essential ' 
in  the  manner  described  earlier  (§§  81-86)  of  the  regenerative  arj 
hyperplastic  proliferation  of  tissue.  They  may  be  distinguished  fro; 
simple  regenerations  by  the  fact  that  they,  at  least  in  a  part  of  the' 
course,  are  accompanied  by  circulatory  disturbances  and  pathologio 
exudations,  especially  by  an  immigration  of  lymph oeiftes  and  lencocytes,  aii. 
that  these  have  a  modifying  action  upon  the  course  of  the  process. 

The  granulation  tissue  which  is  formed  during  the  course  of  an  inflai' 
mation  is  nothing  more  than  an  embryonic  tissue  arising  through  oi 
proliferation   and  infiltrated  with    leucocytes   and  lymphocytes,      i 


tti,  polyniicli'iir  li 
C],  murtinucli-nill 
connective  tissue. 


ills  froma  wound-granulalion  (Miiller's  fluid,  picrocarmintO.  ft.  >rononue» 
is;  h,  different  forms  of  mononuclear  flbroblaats ;  c,  libroblast  with  two  nmi 
I;  (/,  fibroblasts  in  the  stage  of  connective-tissue  formation ;  e,  fully  deveW 


'the  beginning  it  consists  essentially  of  cells  and  new-formed  hlood-V£&\ 
which  al  first  And  their  sui)i)()rt  in  the  ground-substance  of  the  tissue  fr  n 
which  Ihcy  pass  out,  l)ul  soon  foi-m  for  themseles  a  new  (ironnd-sHbstui'i. 
The  cells  of  the  granulation  tissue  are  in  part  proliferated  tiss  >■ 
cells  (  Fig.  21.-),  />,  c,  d),  in  i)art  polynuclear  leucocytes  ((^i)  and  monoM- 
clear  lymphocytes  («).     In  most  cases  the  proliferated  cells  are  coma- 


GRAXILATIOX    TISSUE.  351 

jive-tissue  eolls  which  hitcr  ])roduc('  oonnoctivo  tissue  (<J,  r)  and  are 
llierefore  kiiinvu  us  fibroblasts.  The  fiiiuiuhition  tissue,  lu)\vever,  may 
'iso  eoutaiu  the  derivatives  of  other  tissues,  for  example,  of  the  i)erios- 
iMun,  uuirn)\v-t  issue,  and  uiusele-t  issue,  in  the  form  o(  osfnthla.sts,  ch(m<lrn- 
/(ists,  and  .sarrohhi.st.s,  Avhieh  air  abh^  to  form  bone,  eart  iia.ii'e,  and  muscle. 
I'urtlu'r,  newly  formed  ;iJ<iu(h(J(tr  rpifhcliinii  may  occur  within  .glands, 
/Idle  in  mucous  ineml)ranes  and  in  the  outei-  skin  new- formed  .sv/r/Wrv- 
pHheliiim  may  be  found  in  or  upon  the  granulat  ion  tissue,  tlicsc  hein-- 
•ble  to  produce  ('piflicUal-tissuefoniiatioiis.  The  fibroblasts  of  the  granu- 
lation-tissue are  large  polyuuu-phous  cells,  Avith  clear  luu-lei  (Fig.  215, 
;),  and  in  i)art  possess  loug  processes.  Young  forms  m- it  bout  processes 
'lay  resemble  epithelial  cells  and  are  therefoie  classed  with  the  so-called 
pithelioid  cells.  With  the  help  of  theii- ]u'ocesses  they  cau  ])ush  into 
he  tissue  s])aces,  but  usually  show  no  lively  ainceboid  moAcments. 

In  the  fnrther  development  of  the  granulation  tissue  the  fibroblasts 
|Orm  connective=tissue  fibrillae,  a  portiou  of  the  protoplasm  taking  ou 


'4k. ^d:^ 


^:j 


10.  216.— Scar  fifteen  days  old  (Maximow,  1.   c).     a,  Filjroblasf.s;   6,  polvmori)lioii.s  Ivnipliocvtes 
(polyblasts);    c,  uncliaiij,'ed  lyiiiphocyte  (polyblast).      x  500. 

j.  fibrillar  appearance,  or  tiist  becoming  more  homogeneous  and  then 
'►reducing  tibrillfe  (Figs.  215,  d^  r;  216,  o;  217,  a). 

I  The  polynuclear  leucocytes  of  the  graindation  tissue  (  Fi--.  215,  a) 
^^lSlngfI•om  the  blood  arc?  not  cai)able  of  further  developnu-nt  ;in(l«Mthei- 
zander  farther  or  tinally  die,  i»articularly  those  which  -.is  pii.srorim.sr/r.s 
■ollect  on  the  surface  of  the  tissue  or  in  a'bsces.se.s.  If  bacteria  are  j)res- 
^nt  in  the  ti.ssue  (streptococci,  stai)hylococci,  gouococci,  anthrax-bacilli, 
'•ic.)  the  leucocytes  may  act  an  j>/iaf/ori/frfi  (vu'cropJioors)  nud  aid  in  the 
llestructi<.n  of  the  bacteria. 

i  The  lymphocytes  and  mononuclear  leucocytes  of  the  granulation- 
issue  are  cells  which  for  the  chief  i)art  arise  from  \\w.  blood,  although 
uch  cells  may  later  be  present  in  tlu^  tissue,  and,  increasing  by  division, 


352 


INFLAMMATION , 


may  be  mingled  with  the  cells  of  the  exudate.     Many  of  them  die 
the  granulation  tissue,  as  do  the  polynuclear  leucocytes ;  or,  on  the  oth 
hand,  they  may  change  into  various  cell-forms,  and  from  this  point 
view  they  may  be  designated  polyblasts. 

Enlargement  of  the  cell-protoplasm  and  a  certain  enlargement  ai; 
clearing  of  the  nucleus  give  them  the  character  of  epithelioid  cells ;  y' 
usually  they  are  of  smaller  size  than  fibroblasts  and  their  nuclei  stal 


PI' ' '  I  W  111 '  W  '  Up  I 


Fig.  217. — Tissue  from  a  scar  sixtv-fivi- days  old  (Maximow,  1.  c).    a,  Fibroblasts;   6,?>i,spiD> 
formed  lymphocytes  (polyblasts),  with  elongated  nuclei    embedded    in  the    tissue;    c,  plasma   IL 


darker  (iron-ha-matoxylin  or  methylene  blue)  than  those  of  the  fil')- 
blasts.  i 

By  sending  oid  plump  psendopodia  they  may  take  on  the  most  varied  fop 
(Fig.  216,  h).  On  the  surface  of  smooth  foreign  bodies  they  may  'M 
form  an  epithelial-like  dei^osit  or  covering,  ' 

In  the  development  of  fibrous  cicatricial  tissue  they  may  be  embed  id 
?ii>,  permanent  elements  of  the  same  in  the  form  of  spindle  cells  which  fiu:iy 
can  be  distinguished  only  with  difficulty  or  not  at  all  from  the  ordiujy 
connective-tissue  cells  (Fig.  217,  h,  bj.  Occasionally  they  assume  i,so 
a  character  corresponding  to  that  of  the  so-called  Idasmatocijtes  of  Eaufer 
(Fig.  218,  h),  that  is,  they  form  spindle  or  branched  cells,  coarsly 
granular,  showing  many  vacuoles  and  often  containing  granules  staiidg 
metachromatically  (polychrome  methylene  blue).  Further,  they  j»ii 
assumetheappearanceof  yv/r^s/;/'^^^//.s•  (Figs.  217,  c,  218,  c),  that  is,  rolid 
or  irregularly  formed  cells  having  an  eccentric  nucleus  and  a  bright  iin- 
tral  and  a  dark  granular  peripheral  plasma.  These  i^lasma-cells  1  er 
die  or  take  on  the  appearance  of  the  first-named  forms. 

The  derivatives  of  the  lymphocytes,  poli/hlasts,  are  those  cells  w  cli 
show  the  greatest  activitv  in  the  granulation  tissue  as  phagocytes,  ud 


GRAN ULATIOX    TISSl'K. 


35:i 


I  not  only  take  up  bacteria  but  also  cells,  red  blood-cells  and   leucocytes 
|(Fia'.  -14),  and  destioy  them  or  cany  lliein  away. 

Thev  liave  also  an  especial  inclination  In  form  multinucleated  jjiant- 


FiG.  218.— Plasma  cells  and  klasmatocytes  within  scar  tissue,  forty  days  old   (Maximow,  I.  c). 
a,  Fibroblasts;   b,  klasmatocytes;   c,  plasma  cells;    d,  blood-vessel.     X  500. 


cells,  and,  indeed,  syncytial  forms,  that  is,  through  {he  conjhirnrr  of  crlls 
'  hjlny  in  close  contact.  This  is  most  frequently  ol)served  when  larger  or 
,  smaller  foreign  bodies  or  necrotic  portions  of  the  tissue  lie  within  the 

LMannlation  tissue  (Fig.  219,  d),  and  they  are  therefore  designated  as 
i  foreign=body  giant=cells.  Soluble  snbstances,  for  example,  catgut  sntures 
j  or  necrotic  muscle-substance,  can  be  gradually  dissolved  by  them. 

The  presence  of  certain  forms  of  bacteria  (tubercle-bacilli  and  lepia- 
;  bacilli)  can  also  lead  to  their  formation. 

j       The  blood-vessels  of  the  granulation  tissue  arise  through  oflf.shoots 
jfroni  the  old  vessels  (see  Fig.  lOGj,  which  very  early,  even  at  tliat  time 

in  which  the  immigration  of  leucocytes  takes  place  (Fig.  L'2<»,  l>,  />,),  show 


»W*"^ 


^"iv.^^^*""'^'*'''''^  ''"'''  ''ficapsulated  in  the  subcutaneous  tis-sue  (alcohol,  Uismank  brnwni.    </,  Hair;  /j, 
nbrous  tissue  ;  r,  proliferating  grraiiulation  tissue  ;  t/,  piant-i-elis.     X  IW. 

(proliferative  processes  (a),  and  in  the  formation  of  granulation  tissue 

I  take  on  a  very  lively  proliferation.     The  young  granulation  tissu<*,  as  :i 

result,  becomes  i)ermeated  by  a  great  number  of  blood-\essels,  so  tiiat  it 

[acquires  a  red  ;ipp(>aranc<'.      i)niing  the  traiisfonnat  i( f  the  granulat  ion 

i  L'3 


3.J4: 


TNTLAMMATION. 


Fig.  220.— Cross-section  of  blood-vessel 
from  the  deep  layers  of  the  skin,  forty  hours 
after  painting  the  skin  of  a  rabbit  with 
tincture  of  iodine  (Flemming's  solution, 
safranin).  «,  Endothelial  cells  with  mi- 
toses; b,  b,,  leucocytes.    X  350. 


tissue  into  connective  tissue  or  scar-tissue  tliere  occurs  an  obliteratioi 

of  the  vessels  and  the  scar  becomes  pale. 

The  structure  of  the  granulation  tissue,  the  origin  and  the  fate  of  th 
cells  contained  in  it.  have  been  for  decades  the  object  of  mvestigation  and  discussioi 
and  even  to-day  not  all  of  the  questions  can  be  regarded  as  solved.  It  has  been  de^noi 
strated  beyond' doubt,  liowever,  that  the  builders  of  cicairicial  tissue,  the  fibroblasts,  ai 

derivatives   of  the  fixed    cunnectire-tissue    cells. 

further,  it  is  certain  that  the  polynuclear  Icuci 

cytes  arise  from  the  blood  and  undergo  no  fu 

ther    development.      The    origin    of    the   sma 

mononuclear  cells  which   resemble   the   lymjilK 

cytes  and   the  mononuclear  leucocytes  "  of   tl 

blood  is  still  a  matter  of  dispute,  as  is  alsn  tl 

role  which   they   play  within   the   granulatioi 

tissue.     Even  in  the  year   1876,  on  the  gruui; 

of  experimental  investigations,  I  expressed   tl 

opinion   that    they    were   capable   of  a  fmili. 

development  into    epithelioid   cells  and    th:it    : 

the  time  of  their  formation  and  transform;!  tii 

they  exert  phagocytosis  and  take  up  other   eel 

and   digest  them    and    that    they    can   becon 

changed  into  permanent  elements  of  cicatrici 

tissue.     I  have  further  demonstrated  that  uiid( 

especial   conditions  they  form    syncytial    gian 

cells. 

Maximoiv,  through  investigations  carried  on  in  my  laboratory  in  the  years  1901' 

1902,  has  confirmed  the  view  that  the  mononuclear  leucocytes  and  lymphocytes,  aft' 

passing  out  from  the  blood-vessels,  may  undergo  further  development,  and  has  demo:: 

strated  that  within  the  cicatricial  tissue  they  take  on  in  part  the  appearance  of  Ida 

matocytes,  plasma-cells,  and  mast-cells,  also  in  part  appearances  similar  to  those  of  t) 

ordinary  fixed  connective-tissue  cells,  so  that  finally  differentiation  of  the  two  cell-fon 

is  no  longer  possible.     They  also  change  in  part  to  fixed  connective-tissue  cells,  but  > 

not  produce,  as  I  formerly  assumed,  the  fibrillary  ground-substance. 

With  reference  to  the  varied  forms  which  these  cells  show,  Maximow  has  designati 
them  pAyblasts.  Much  more  appropriate  would  be  the  term  polymorphocytes  i\ 
poikilocytes,  although  the  latter  term  is  in  common  use  for  various  forms  of  degeneratii! 
red  blood-cells. 

The  differentiation  of  the  different  cell-forms  as  given  above,  rests  essentially  up( 
differences  in  the  structure  of  the  protoplasm.  Plasma  cells  (Unna)  or  the  "kriuiK 
zellen"  {von  Marschalko)  are  mononuclear,  roimd  or  oval,  at  times  elongated  cells  th 
stain  intensely  with  methylene  blue  and  possess  an  eccentrically  placed  nucleus  showi 
a  chromatin  network  and  five  to  eight  chromatin  granules.  At  the  peripheiy  of  t 
cell  the  protoplasm  is  more  densely  chunped,  so  that  there  is  formed  a  lightei-  ai 
surrounding  the  nucleus.  The  kiasmatocytes  {Ranvier)  are  spindle-shaped,  branched 
stellate  cells  with  blunt  or  swollen  ends  and  a  granular  protoplasm  that  often  contai 
little  vacuoles.  The  mast-cells  (Ehrlich)  are  round  or  fiat  or  spindle-shaped  cells,  wi 
numerous  distinct  coarse  granules  that,  with  the  basic  aniline  stains,  show  an  inter 
metachromatic  reaction. 

Cells  of  the  character  of  lymphocytes,  leucocytes,  plasma-cells,  kiasmatocytes.  a 
mast-cells  occur  even  in  normal  tissue  and  are  regarded  by  some  authors  as  esjicc 
forms  of  tissue  cells  and  bj^  others  as  cells  arising  from  the  blood.  According  to  \\1 
we  know  of  their  occvu-rence  the  most  correct  visw  is  probably  that  which  regards  th( 
as  different  stages  of  development  of  a  mesenchjiiial  group  of  cells  of  an  especial  ki 
that  are  to  be  separated  from  the  tissue-building  fixed  cells,  and  to  this  group  tht, 
should  be  added  also  the  polynuclear  leucocytes  and  the  eosinophile  cells.  Certj' 
stages  of  development  are  present  in  the  blood,  others  are  found  in  the  tissue  and,  inde( 
partly  in  especial  tissue-formations  (lymphadenoid  tissue,  bone-marrow),  and  partly 
ordinary  connective  tissue.  Under  certain  conditions  the  individual  forms  may  p.- 
into  one  another,  as,  for  example,  lymphocytes  may  become  transformed  into  plasij 
cells  and  klasnratocytes  into  mast  cells. 

The  mononuclear  cells  that  collect  so  quickly  in  an  inflammatory  area  arise,  for  t 
chief  part,  from  the  blood-vessels.  When  the  given  cell-group  occurs  at  the  place 
inflammation  (as,  for  example,  perivascularly  situated  kiasmatocytes  or  lymphocyti 
they  may  increase  by  division  and  take  part  in  the  formation  of  the  cellular  collect io  . 
In  scar  ti.ssue,  for  example,  polyblasts  of  the  appearance  of  kiasmatocytes  may  char^^ 
again  into  cells  corresponding  to  amoeboid  lymphocytes. 


IXFLAM.MATOHY    NEW-FORM  ATION      OF     TISSUE.  355 

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356 


INFLAMMATION. 


Entziindungi 
Entziindimg.     D. 


medi 


Path. 


Bd 


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Woch.,  1SS6. 

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1890. 

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1879 

TJnna:    Granuloplasma.     Histopath.  Atlas,  Hft.  6,  1903. 

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Ziegler,  E.:  Exp.  Unters.  iiber  die  Herkunft  derTuberkelelemente,  Wtirzbiirg,  187^; 
Unters.  iiber  pathologische  Bindegewebs- u.  Gefassneubildung,  Wiirzburg,  187( 
Beteiligung  der  Leukocyten  an  der  Gewebsneubildung.  Verh.  d.  X.  interna, 
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Ziegler,  K.:  Oedem.  d.  Haut  u.  d.  Unterhautzellgewebes.  B.  v.  Ziegler,  xxxvi.,  190  j 
See  also  §  94  and  §  97.  1 

§  96.  If  upon  any  part  of  the  body-surface  there  occurs  an  ope 
wound,  which  does  not  become  infected  with  bacteria  or  seriously  iij 
jured  in  any  way,  the  edges  and  base  of  the  wound  after  twenty-foi 
hours  become  deep-red  and  somewhat  swollen.     The  individual  constitu 

ents  of  the  tissue  can  still  \\ 
clearly  recognized,  only  the  ti; 
sue  appears  somewhat  swollej 
and  here  and  there  small  shrci 
of  necrotia^tissue  may  be  seel 


^^fl*#5ft^/*^5^t^^^^^-?«^ 


Fig   Ji     A\(mnd  grinul  iti(  ns   firm  nr 
witli  tlbrinopuruleia  n\eiin/  niiilki  s  tlm  1   1 
Im)      o,  Gianulation  tissue     h  flbnn  iiuiuhnt 
bloo(l\iss(K  135 


small  red  papules,  which  rapicy  i 
increase  in  number  and  size,  Ij- 
come  confluent,  and  after  t') 
to  three  days  form  a  granuir 
red  surface — a  granulation  si- 
face.  This  is  covered  witla 
more  or  less  abundant  wound  p- 
ci'etion,  wliich  forms  a  gray,  j)- 
latinous  layer,  later  becomilg 
more  yellow  and  creamy.  Ijis 
layer  consists  of  a  coagtilde 
e.ruddfe  and  numerous  poly  i- 
clear  leucocytes. 

The  changes  which  the  fi'- 
face  of  the  wound  shows  an  in 
the  first  two  days  dependent  u  'm 
the  local  hyperj^mia,  and  thtjii- 
filtration  of  the  tissue  with  )1- 


HEALING    OF    WOINDS,  ;i57 

hilar  and  fluid  exudate,  and  upon  the  swellinj;  and  li(iuefaetion  of  tlie  tis- 
sue; aseailyaslhe  second  day  there  is  a(hled  tiiercto  a  lissuc-prolil'cralion 
with  new  -Corjnation  of  vessels,  U'adini;-  to  the  (U'veh)i)nient  of  wound- 
granulations.  After  a  few  days  there  will  lia\e  dt'veloped  in  the  wnmid 
i\  (f ran i(l(i! Ion  1  issue  (Fv^.  221,  a)  consist i)i(/  of  Jihrohldsts  and  Irnroci/h s.  mid 
rich  in  iridc  r(sscls  (c),  and  in  -wliich  there  \ery  soon  ajjpeais  a  Ji/nil/ar 
(/r(nind-si(hst(incc.  Theleneocytes,  which  belonj;-  chielly  lo  the  i)olyniU'lc:ir 
form,  are  foundin  all  the  layers  of  the  skiuin  fiesli  juraiinlatioiis,  i)iit  heap 
themselves  pai'ticularly  in  the  superlicial  strata,  and,  cmhcddrd  in  Jihrin, 
cover  over  the  surface  of  the  granulation  tissue  (i).  The  libroblasts 
are  found  most  abundantly  in  the  deeper  layers  (Fig.  221,  a),  and 
here  the  new-formation  of  connective  tissue  ])roceeds  most  actively. 

When  a  certain  degree  of  fibrilhe-formatiou  has  been  re:.ched,  the 
process  comes  to  a  standstill,  the  remains  of  the  fibroblasts  with  their 
miclei  lemain  as  lixcd  connective-tissue  cells  (Fig.  215,  c),  continue  to 
live,  and  attach  themselves  to  the  surfa<'e  of  the  bundles  of  iibrilhe. 
The  process  has  tlieu  reached  its  termination — the  granulation  tissue  lias 
become  scar-tissue. 

In  open  wounds  of  the  skin,  when  infection  does  not  disturb  the  \ 
course  of  healing,  the  formation  of  granulation  tissue  lasts  until  the  \ 
wound  is  again  covered  with  epithelium.     The  regeneration  of  the  latter   1 
proceeds  from  the  edges,  the  epithelium  gradually  pushing  itself  o\er  the 
granulations.     With  the  formation  of  connective  tissue  the  reproductive 
processes  essentially  terminate,  but  transformation  processes  continue  in 
the  cicatricial  tissue  for  some  length  of  time.     Shortly  after  its  formation  , 
the  cicatrix  is  rich  in  blood  and  appears  red ;  later  it  loses  a  portion  of  ' 
its  vessels  through  their  obliteration,  becomes  pale,  and  contracts  to  a 
volume  much  less  than  the  original.     Large  scars  of  tlie  skin  show^  per-  - 
inanently  a  smooth  surface,  since  the  iiapillary  bodies  are  not  again 
'formed  or  only  imperfectly  (Fig.  223,  e).     The  tissue  of  the  scar  remains 
ifor  several  months  abnormally  rich  in  cells,  but  in  the  couise  of  time 
becomes  poorer  in  cells  and  harder,  and  comes  to  contain  elastic  libres. 

When  the  healing  of  a  wound  occurs  in  such  a  manner  that  the  tissue- 
defect  is  closed  by  the  formation  of  a  grainilation  tissue  visil)lc  to  the 
iiaked  eye,  the  process  is  designated  repair  hif  second  intention  {per  secun- 
dum intentionem). 

Tlie  healing  of  incised  wounds  of  the  skin,  whose  edf/es,  united  hy 
Isutures,  f/rou- t/)f/ether  Jnj  first  intention,  takes  i»lace  in  essentially  the  same 
'manner  as  the  healing  of  an  open  wound  by  second  intention;  but  the 
;])rocesses  of  intlammaTion,  proliferation,  and  ncw-foi-mation  of  tissu(^are 
jless  prominent,  partly  because  they  take  ])lace  below  the  skin,  and  ]>artly 
because  they  are  of  much  less  extent  and  intensity. 

The  result  of  such  a  cut  is  always  a  more  or  less  abundant  cxndat  ion 
fon  the  edges  of  the  wound,  formiiig  a  coagulated  mass  often  contain- 
ling  blood  (Fig.  222,  c),  which  glues  together  the  opposing  wound-sur- 
[faces.  Very  soon  there  arises  an  innainmatoiy  infiltration  (»f  the  edges 
iof  tlie  wound,  which  varies  gieatly  in  dilfcrcnt  cases,  and  when  tliccomse 
iof  repair  isasei)tic  never  reaches  any  signilieant  degree  (//,  // ),  attaining 
jits  maximum  in  from  two  to  four  days,  diminishing  from  the  fifth  to  the 
iseventh  day,  and  ctmipletely  disai)i)earing  at  or  soon  after  the  end  of 
|the  S(H'ond  week.  The  intlammatoiy  infiltration  is  usually  greater  in  the 
neighborhood  of  the  wound-sutures  "than  at  the  edges  of  the  Mound. 

As  early  as  the  second  day  regenerati\e  processes  of  proliferation 
l)egiu  in  the  connective  tissue  and  in  the  vessels,  and  lead,  in  th<'  coiirs<i 
of  several  days,  to  the  formation  of  an  emlnvonic  tissue,  which  lies  partly 


358 


IXFLAMINfATTON". 


in  the  spaces  of  the  connective  tissue  at  the  edges  of  the  wound  (Fifi 
222,  /),  and  partly  extending  into  the  open  space  of  the  wound  itself  (f 
and  here  gradually  grows  into  the  coagulum  which  is  present  and  replace 
it.  This  tissue  is  usually  present  in  varying  quantity  in  different  pari 
of  the  wound  (Fig.  222),  and  may  be  entirely  absent  in  places.  After 
certain  number  of  days,  the  time  varying  according  to  the  size  of  tl:; 


V-JT^ 


.^^-.y.  rz'jz 


Fig.  223.— Healinpr  of  incised  wound  of  skin  united  by  suture  (Flemming's  solution,  safranin).  Prf  r- 
ation  made  on  the  sixth  day.  a.  Epidermis :  h,  eorium  ;  c,  fibrinous  exudate,  in  part  haemorrhagic  ;i. 
newly  formed  epidermis,  containing  numerous  division-flgures,  and  with  plugs  of  epithelium  exten  (? 
into  the  underlying  exudate  ;  e,  division-figures  in  epithelium  at  a  distance  from  the  cut ;  /,  prolifera^R 
embryonic  tissue,  developing  from  the  connective-tissue  spaces,  and  containing  cells  with  nuclear  divi  i- 
flgures,  and  in  part  also  vessels  with  proliferating  walls:  g,  proliferating  embryonic  tissue  with  leucoc;^J; 
h,  focus  of  leucocytes  in  deepest  angle  of  wound ;  i,  fibroblasts  lying  within  the  exudate,  one  showi;  a 
nuclear  division-figure ;  k,  sebaceous-gland ;  ^  sweat-gland.    X  70.  ! 


wound,  the  thickness  of  the  exudate  between  the  edges  of  the  wound,  s,d 
the  inteusily  of  the  proliferation,  the  masses  of  embryonic  tissue  grow  g 
from  the  edges  of  the  wound  blend  together,  and  there  follows  the  foriV 
tion  of  young  connective  tissue,  which  joins  the  edges  of  the  woundi)- 
gether,  and  at  the  same  time  extends  also  into  the  old  tissue,  so  that  ;ie 
boundary  between  the  old  and  the  new  tissue  becomes  indistinct. 

While  connective  tissue  is  being  formed  in  the  deeper  parts  of  le 
wound,  the  epithelial  covering  on  the  surface  is  also  being  regenerf^d 
(Fig.  222),  and  indeed  in  this  manner,  that  the  epithelium  pushes  c.er 
the  wound-surface,  and  through  a  continuous  cell-division  (d,  e)  foas 
an  epithelial  covering  consisting  of  many  layers.     The  epithelium  My 


J 


HEALING    BY    FIKST    1  NlKXI'lOX, 


:^r)0 


push  across  the  wouud-suirncc  eviMi  lu'lort'  :i  new  roiiiial ion  of  cells  Ikls 
taken  i)l:u*e. 

The  younc:  couueetive  tissue  of  the  sear  uniting  tlie  edjifes  of  the 
S«ronml  is  distiiiuuisliable  ft)r  a  ]ou^  time  from  the  iiei<:;hl)oriii<i  ohU-r  tis- 
Isue  throu^di  its  riehm-ss  in  cells  (Fi.u'.  223,  </,/),  as  well  as  lhi(>n<;h  11h^ 
lliner  librillatiou  of  its  tirouiul-snhstanee;  and  in  lar^e  ineiscd  \vonMds 
lof  tlie  skin  there  may  be  found  in  it,  here  and  there,  after  the  lapse  of 


■'""^^ 


Fig.  233.— Cutaneous  portion  of  a  laparotomy  cicatrix,  sixteen  days  after  the  oi)eratlon  (Miiller's 
fluid,  haeraatoxylin.  Van  dieson's).  n.  Epithelium;  h,  corium;  c,  subcutaneous  fat  tis.sue ;  d,  scar  In 
corium;  e,  new  epithelial  covering ;  /,  scar  in  fat  tissue.    X  38. 

I  weeks  or  even  months,  slight  evidence  of  ])i"oli feral  ion  and  inflammalion.s. 

i  In  general,  howevei",  transformation  ]>ro('esses  gradually  occur  in  tin; 
hlanchiiig  scar,  so  that  its  tissues  come  to  ap])i<)ach  more  closely  to  the 
iiornial.  and  linally  the  place  of  the  incision  can  no  longer  be  easily  rec- 
ognized.    If  the  wound  lieals  by  tiie  interi»osit  ion  of  abnndant  embryonic 

•tissue,  there  may"  occur  a  defect  of  tlie  i)ai)illary  bodies  (i'ig.  22.'),  r),  so 

[  that  the  scar  remains  smooth. 

jj  07.   When  thei'e  is  found  upon  the  surface  of  an  inflamed  serous 

■  membrane  (Fig.  224,  a)  an  adherent  layer  of  fibrin  (/>*,  there  n^nally 
developcpiickly  beneatli  it  granulation-formations.  The  earliest  begin- 
nings of  these  can  be  seen  as  soon  as  tli«'  loiirtli  day  after  the  fornialion 
of  the  fibrinous  dei)osit,  and  they  <'<»iisist   at  lirst  of  the  ajjpearancc^  of 

'  Jibrobla-stfi  (f)  and  i)olyblasts  in  the  deepest  layers  of  the  fibrinous  mem- 
brane.     These  arise  through  the  ])rolifeiat  ion  of  the  conne<-ti  vet  issue 

i  cells  of  the  affected  serous  mend)iaiie.  and   wander  to  the  .surface,  and 

'  into  the  fibrin.     In  association  with  this  Dhenomeiion  thei-e  follows  v«n-y 


360 


INFLAMMATION. 


Fig.  234.— Fibrin  deposit  and  beginning  formation  of  granulaticj 
tissue  in  a  fibrinous  pericarditis  five  days  old  (Miiller's  fluid,  haemi: 
toxylin).  a,  Epicai-diuin;  h,  flbrin-membrane ;  c,  dilated,  congests! 
vessels ;  d,  round  cells  infiltrating  the  tissue ;  e,  lymph-vessel  filled  wr 
cells  and  clots ;  /,  fibroblasts  within  the  deposit.    X  150.  I 


soou  a  new-formation  of  blood-vessels,  and  in  the  course  of  days  or  o  ■ 
weeks  there  is  developed  npon  the  surface  a  vascular  embryonic  tissue  0]| 
granulation  tissue,  which,  when  the  overlying  fil)riu  layer  is  very  com' 
pact,  lifts  this  up  in 
toto  (Fig.  225,  b,  c)  ; 
or  penetrates  into  the 
interstices  of  the  fi- 
brin-membrane (Figs. 
224,  /;  226,  h,  d), 
and  in  the  course  of 
time  reiilaces  the  fi- 
brin. Eemains  of  the 
fibrin  (Fig.  226,  e) 
may,  however,  often 
persist  for  a  long 
time,  weeks  or 
months,  within  the 
granulation  tissue. 

In  the  formation  of 
the  granulation  tissue 
and  the  development 
of  scar-tissue  the 
epithelium   (endothe-  j 

lium)  of  the  serous  membranes  takes  no  part,  since  it  produces  no  fibrcj 
blasts.  On  the  otlier  hand,  the  products  of  the  inflammatory  prolifeKJ 
tion  become  covered  later  with  epithelium.  i 

The  final  result  of  the  process  is  the  formation  of  connective  tissu<; 
which  leads  either  to  a  ihicl-ening  of  the  serosa  which  had  been  covere; 

with  fibrin,  or  to  an  adh< 
ston  of  the  opposing  surfad] 
of  the  serous  mrmbrane,  sj 
that  the  inflammation  maj 
be  designated  as  adhesiv\ 
The  result  in  individu;! 
cases  depends  partly  upcj 
the  amount  of  the  fibr:' 
deposit  and  i)artly  upci 
the  situation  of  the  aflecj 
ed  organ,  and  its  conditi(j 
during  the  process  of  heijj 

ifl"'\%i^^'PS.-#"1  '"^Small    deposits    j 

Mi    ••i»4C^#^^^^^fe^^4§^f  /    i  fibrin,  limited  to  one  su  ■ 

face  of  the  serous  mei 
brane,  lead  only  to  thici 
enings  of  the  seros:* 
wliich, becoming  pale  wi| 
the  obliteration  of  the  v<i- 
sels,  are  represented  finsf 
ly  by  white  thickeuius 
frequently  designated  } 
tendinous  spots.  T? 
firm  glueing  together  of  two  serous  layers  by  an  abundant  deposit  of  fibu 
leads  also  to  a  firm  adhesion  of  the  "same  through  the  abundant  forirh 


i^^'i 


in  the  pleura,  in 
;'  duration  (alco- 
ii:i ;  l>,  very  vas- 
scles,  and  gran- 


ORGANIZATION    OF    KNIDATHS. 


:?(ii 


Fig.  231).— Formation  of  granulation  tissue  in  the  fibrinous 
deposits  of  a  pericanlitis  several  weeks  old  (Miiller's  fluid, 
liaematoxylin,  eosin).  a,  Epicardium  ;  h,  deposit  on  the  epi- 
i-ardium.  consisting  of  granulation  tissue  (cf),  and  flbrin  (c). 


f  ion  of  connect  ive  1  i.ssno.  In 
tlu!  cas(^  of  a  smaller  amount 
of  liltiin,  and  rcpcatctl  rub- 
bing of  the  ntemlnanes  upon 
each  other,  thei«^  «le\t'h)p 
only  loose  wr)iihra>inii.s  or 
sirinf/i/  (iilhr.sion.s,  Avhich  still 
peiiiiit  the  serous  surfaces 
to  ]no\e  iii)on  one  another. 
AVry  large  amounts  of  fihrin 
may  also,  under  ceitain  con- 
ditions, in  pai-t  i)ermanently 
resist,  absorption,  so  that 
they  remain  lyinjiAviihin  the 
newly  formed  connective 
tissue,  and  then  usuallx-  be- 
come (■((/(■!  lied. 

Coagulated  exudates  in 
the  lun«;s  may  (luickly  be- 
come liquetied  and  abmrhril, 
but  it  also  happens  that 
their  removal  may  Ite  asso- 
ciated with  a  connective- 
tissue  prolifei-ation,  Avliich 
leads  to  an  induration  of  t/ir 
lung.  The  i)roliferation  i>r()- 
ceedinji;  from  the  lunj;  tissue 
leads  either  to  ii  thickening 

of  the  septa  (Fig.   227,  a,  h)  or  extends  into  the  exudate  lying  in  the 

alveoli,  in  the  form  of  an  embryonic  tissue  {d,  c),  which  later  comes  to 

Icoiitain  newly  formed  blood- 

! vessels  (//). 

{      Hasses  of  coagula  with= 

)in  blood=vessels,  Mhich  are 

culled  thrombi,  give  rise,  in 

case  no  infection  occurs,  to 

au   intiammatoiy  —  that   is, 

associated  Avith  cell-emigra- 

.tiou  — ])i<)liferatiou    of    the 

ivessel-wall,     a    j^rolifendijig 

\rnseuliti.s.      This  i)rocess  cor- 

Iresponds  exactly  to  the  iii- 

jtianimatory  piolifeiation  of 

the  serous   niembianes.     It 

is    entirely     immaterial 

whether  the  throndiosis  has 

heeu  caused  by  a  preceding 

inflammatory  process  or  by 

any  other   comlitions,   inas-  "^M^^"'"'''^'^. 

much  as  the  i)resenc(i  of  the 

mass  of  coagulum  is  suffi- 
cient to  cause  inflammation 

and  tissue-proliferation. 

i      The   first   change    intro- 


_<i§^^' 


/' 

d 


Fio.  227.  — Intraseptal  and  inirii-alviMiai  furinatlon  of  con- 
nective tissue  in  tlie  lung  (alcohol,  liaMriatoxyllni.  <i.  Thick- 
ened tlbrocellular  alveolar  septum,  in  part  liillltraled  with 
round  cells  (/<);  c,  Ilhrinocellular  exudate  In  the  alveoli; 
(I,  ititra-alveolar  formative  cells;  c,  stnmd  of  splmlUM-ell 
llbrohliists;  (/.  intra-alvef)lar  newly  formed  blood-vessel. 
X  2U0. 


362 

duced  in  the  substi= 
tution  of  thethrom= 
bus  by  connective 
tissue  is  here  also 
the  appearance  of 
fibroblasts  (Fig.  228, 
/<),  which  arise  from 
the  vessel-wall,  and 
later,  with  the  aid  of 
vessels  growing  in 
from  the  vessel -wall 
and  its  neighbor- 
hood, form  an  em- 
bryonic tissue,  which 
ultimately  changes 
into  connective  tis- 
sue. The  complete 
substitution  of  an 
obturating  throm- 
bus or  embolus 
leads  to  the  obliter- 
ation of  the  vessel- 
lumen  by  vascular- 
ized connective 
tissue  (Fig.  229,  g) ; 
the  substitution  of  a 
formation  of  fibrous 


INFLAMMATION. 


1 


J* 


^!''W^M 


#-^ 


'i^j 


rifi  2^8  — I>t  \i  li  i"i'< 'If  rif  tnihi\(iiiii  tl'^sllP  in  a  tliioniliost  d  feme 
artery  of  an  old  man,  tlnee  week^  aftu  li^'dtion  (aNdliol  liimatowli 
a.  Media;  ?>,  elastic  limiting  niembiane;  t,  intiina  tliu  kened  tliroi  i 
older  inflammatory  protessf  & :  d,  coagulated  blood  ,  t,  <  ellular  inflltrat  i 
of  the  media,  /,  of  the  mtima;  f/,  round  cells,  parth  in  the  thromt, 
partly  between  it  and  the  intlma;  h,  different  forms  of  flbrobls;. 
X  3(10. 


parietal  thrombus,  on  the  other  hand,  results  in  tj) 
thickenings  of  the  vessel-wall.     As  the  result  of  ii 


f 

:  :.--■ ":  ■  -  -•  "■  -V*'':'?'*;v^ 


•v-'-:\' 


II  e  h     d  c,  '.I 

Fig.  239.— Periphery  of  a  healing  pulmonary  infarct  (Miiller's  fluid,  haematoxylin,  eosin).  a,  E  xl- 
extrivvasate  chanced  iiito  a  yellowish  granular  mass;  b,  necrotic  alveolar  septa  without  nuclei ;  c>r'ly 
formed  connective  tissue;  c/,  vascular  granulation  tissue  within  the  alveoli;  c,  fibroblasts  within  a, oil 
containing  the  residue  of  the  h;pinorrhage ;  /,  artery ;  {/,  Viiscular  connective  tissue  formed  withii  he 
artery  at  the  place  of  the  embolus.     X  40. 


ORGAXIZATIOX    OF    NECROTIC    TISSUE 


363 


iphleb 


imperfect  subslitutiou  and  liquefaction  of  the  i)art  not  substituted,  there 
arise  strands  and  threads  of  connective  tissue,  which  cross  the  lumen  of 
the  vessel.  The  ealcilication  of  portions  of  thrombi  not  rei)hiced  by 
connective  tissue  leads  to  the  formation  of  vessel-stones  farterio-  or 
)oliths). 
Necrotic  tissue,  Mhich  cannot  be  se(iuestr;ite(l  nnd  (lischar<;ed  exter- 
nally, is  also  replaced  by  a  vascuiar  connective  tissue,  wiiich  becomes 
converted  into  scar-tissue;  and  this  subslitut  inn  takes  phu-e  in  the  same 
manner  as  in  the  case  of  librinous  exudati's  and  thrombi.  The  requisite 
condition     for    this 

•  substitution  is  that 
the    necrotic    tissue 

;  shall  contain  no  sub- 

Istances  (bacteria) 
which  hinder  tis- 
sue-proliferation or 
excite  se\ereintlam- 

,  mation.     In  general 

;if  is  immaterial  how 

I  the  necrosis  has  oc- 

jcurred,  and  whether 
the  necrotic  tissue  is 

I  free    from    exudate 

jor  is  infiltrated  with 

[  exudate    or    blood. 

I  The  first  phenom- 
enon    leading     to 

•  healing  is  the  asso- 
ciation with  the  iu- 
Hammatory  exudate, 
in  the  neighborhood 

;  nf  the  necrosis,  of  a 

i  tissue-proliferation, 
wliieli  produces 
granulation  t  i  s- 
sue,  which  grows 
toward  the  necrotic 
tissue  (Fig.  229,  d, 

c),  dissolves  it,  and  finally  replaces  it.  If  this  process  is  not  disturbed 
by  any  influence  whatever,  even  very  large  tissue-necroses  (f(»rexamph', 
a'ha'inonhagic  infarct  of  the  lungs)  may  in  the  couise  of  weeks  and 
months  l)e  ma(h'  to  disa])pear  and  may  be  i'ei)hiced  by  c(Minective  tissue. 
It  may  also  hap])en,  however,  that  certain  tissues  resist  abs()ri)ti()n,  or 
that  tlie  dexelojiment  of  granulation  tissue  stops  so  eaily  that  remains  of 
the  nccroHcd  iisHnrs  persist  and  later  become  calcified. 

When,  as  the  result  of  an  inlhimjuation  or  ischa-mia  within  an  organ, 

^  only  the  more  sensitive  elements  (be— for  exam])le,  epithelial  or  miisch^ 

:  cells— while  the  connective  tissue  i-emains  intact,  the  ai)soii)ti»>n  of  the 

Miecrotic  portions  takes  place  very  (piickly,  and  there  is  formed  within 

^  a  short  tinu^  usear  or  callus  of  eomirefi  re  tissue  (  Fig.  2.S0.  r),  in  whicii  the 

I  specific  tissue-elements  ai-e  lacking. 

]        Pus  is  (juickly  «/;.vor/>rf/ from  small  abscesses,  an«l  the  drfrfl  eln.snl  hi/ 

!  granulation  and  scar  tissue.     Large  amounts  of  pn 

';  the  body-cavities  and  from  the  lungs. 


Fk;.  21^0.— Fibroid  area  in  heart-muscle.  Sertlon  tlirouRh  a  muscle-tra- 
becula  wliich  has  undergone  fibroid  rhatiRP  (Miiller's  Huid,  hapmatoxylin). 
a.  Endocardium;  h,  cross-section  of  normal  musclc-cclls ;  r,  hyperplastic 
connective  tissue  rich  in  cells;  r/,  airophic  niusi-if-ct-lls  in  hypen>lastic 
connective  tissue;  f,  dense  connective  tissue,  poor  in  nuclei  and  contain- 
ing no  muscle-cells;  f,  vein,  iti  whose  neighborlMiod  niuscle-c«lls  are 
still  preserved;  g.  small  blood-vessels;  /i, small-celled  iuDltraUon.     X  40. 


IV  be  :ibsorbed  from 


364  INFLAMMATION. 

Abscesses  cause  in  their  neighborhood  a  proliferation  of  granulation 
tissue  which  leads  to  the  formation  of  an  abscess=membrane.  Tbt 
abscess-cavity  may  become  obliterated  through  the  absorption  of  the  pib 
and  the  growing  together  of  the  granulation-membrane  covering  the  Avail- 
of  the  cavity ;  the  abscess  finally  heals  and  leaves  a  scar.  Incompleti 
absorption  may  lead  to  thickening  of  the  pus  and  later  a  cak'ificdtivn  ol 
the  )-f'.siilHe.  If  the  pus  does  not  become  inspissated,  the  abscess  maj 
persist  and  in  the  course  of  time  may  be  increased  in  size  by  secretioi 
from  its  walls. 

Empyemata  may  heal  in  a  similar  manner  to  abscesses  through  tin 
absorption  of  pus.     At  the  time  of  absorption  the  tissues  enclosing  tin 
jius  produce  granulation=  and  scar=tissue,  which  may  reach  a  consider 
able  size  when  the  ^jroccss  of  al)S()r})tinn  takes  a  long  time  (Fig.  L'.';l' 
AYhen  incomitlelely  absorbed,  caleijicaiion  of  the  thickened  pus  may  ocni. 

Foreign  bodies,  so  far  as  they  ai'e  al)Soibal)le  and  exert  no  spcciii 
influence  u^ton  their  surroundings,  are  likewise  dissolved,  and  replace  I  h 
connective  tissue  in  the  same  way  as  are  tissue-necroses  or  fibrin  massi- 
If  they  possess  accessible  interstices,  these  may  be  penetrated  1> 
granulation  tissue.  If  their  mass  cannot  be  absorbed,  they  becom 
encapsulated. 

Literature. 

(Mealiuff  of  Wounds  and  Productive  Inflammation.) 

Anschiitz:  Primarer  Wundverschluss.     Beitr.  v.  Bruns,  xxv.,  1899. 

Barth:   Knocheiiiinplantation.     B.  v.  Ziegler,  xvii.,  1895. 

Baumgarten :   Die  sog.  Orga.nisation  des  Thrombus,  Leipzig,  1877;   Die  Rolle  der  fixt 

Zellen  in  der  Entziindung.     Berl.  klin.  Woch.,  1900. 
Beneke:   Die  Ursachen  der  Thrombusorganisation.     Beitr.  v.  Ziegler.  vii.,  1890. 
Borst:   Chron.  Entzimd.  u.  pathol.  Organisation.     Ergeb.  d.  allg.  Path.,  iv.,  1900. 
Biittnei':    Verb.    d.    Peritonealepithels   bei    Entziindung.       Beitr.  v.    Ziegler.    x.w 

1S99. 
Cassaet.  De  I'absorption  des  corps  solides.     Arch,  de  med.  exp.,  iv.,  1892. 
Chlamsky:   Methoden  der  Darmvereinigung.     Beitr.  v.  Bruns,  xxv.,  1899. 
Cornil  et  Carnot:   Rcgen.  cicatricielle  des  conduits  et  des  cavites  muqueuses.     Arc 

de  mod.  exp.,  1898  and  1900;   Cicatrisation  des  plaies  du  foie.     Sem.  med.,  1S9n. 
Councilman:    Acute    Interstitial    Nephritis    (Plasma-cells).      Jour,    of    Exp.    .Me^ 

189S. 
Enderlen  u.  Justi:   Heilung  v.  Wunden  d.  Gallenblase.     Z.  f.  Chir.,  61  Bd..  1901. 
Foa:    Teller  Niereninfarkte.     Beitr.  v.  Ziegler,  v.,  1889. 
Giovannini:   Lesioni  inflammatorie  e  neoplastiche  della  pelle.     Arch,  per  le  .Sc.  Mei 

x.,  1886. 
Graser:   Die  feineren  Vorgange  bei  Verwachsung  peritonealer  Blatter.     Dent.   Zeit. 

Chir.,  xxvi.,  1888;  Zusamraenheilung  von  serosen  Hauten.     Yerh.  d.  Chir.-Congi 

1895.  ! 

Hallwachs:  Ueber  Einheilen  von  organischem  Material.     Langenbeck's  Arch.,  24  B 

1S79. 
Hamilton:  On  Sponge  Grafting.     Edinburgh   Med.  Jour.,  xxvii.,  1881-82. 
Herbert:  The  Young  Plasma-Cell  in  Chronic    Inflammation.     Jour,    of    Path.,    \', 

1900.  j? 

Hildebrand:   Implantation  v.  Haaren  in  Dermoidcysten.     B.  v.  Ziegler,  vi.,  1890.  [^' 
Hinsberg:   Betheil.  d.  Peritonealepithels  bei  Einheilung  v.  Fremdkorp.     Virch.  Arc, 

l.-)9  Hd.,   1S98. 
Jacobsthal:   Ilistologie  der  Arteriennaht.     Beitr.  v.  Bruns,  xxvii.,  1900. 
Kaneko:   Kimstliche  Erzeugung  von  Margines  falciformes  u.  Arcus  tendinei.     A  . 

i'.iitwickolungsmech.,  xviii.,  1904. 
Kiener  ct  Duclert:   Formation  et  gueri.son  des  absces.     Arch,  de  med.  exp.,  v.,  I!"  • 
Krxickmann:  Heilung  v.  Lederhautwunden.     v.  Graefe's  Arch.,  42  Bd.,  1896. 
Ktister:    Wunden.     Eulenburg's  Realencyklop.,  xxvi.,  1901. 


f 


I 


CHRONIC    INFLAMMATION. 


365 


liatis:   Riiissorbiniento  del  catgut.     La  Riforina  MeiL,  ISOL 

iTeyev:    I'leiiulkuiperperitonitis.     B.  v.  Zieglor,  xiii.,  LS<)X. 

yionckeberg:  \evh.   d.  Pleuroperitonealopithels  l)ei   Kiiiliciluii'j;  voii    !■  rciiKlktH-ptTii, 

i       B.  V.  Ziegler.  xxxiv.,  1903. 

iluscatello:   Condiz.  necess.  alia  produz.  di  aderciize  pcriton.     .Vrcli.  per  k-  Sc.  .Med., 

XX.,  ISOG. 
)clieton:  Transplantation  toter  Knochenteile.     Virch.  Arch.,  124  Bd.,  1S91. 
i'oggi:  La  cicatrisation  immediate  des  blessures  de  I'estomac.     Beitr.  v.  Ziogler,  iv., 

Jena.  1S8S. 
lanvier:  Mecanisme  hist,  de  la  cicatrisation.     Lab.  d'liist.  du  rollege  do  Krance,  1900. 
ioloff;    Rollc  d.  I'leuroperitonealepithels  bei  d.  Entsteli.   d.   Bindegewebsadhasioncn. 

Arl).  a.  d.  Inst.  v.  Baumgarten,  ii.,  1897. 
jalzer:   I'elicr  Einheihmg  von  Frenidkorpern,  Wien,  1S9(). 

jchottlander:  Kern-  u.  Zelltheilung  im  Endothel  d.    entziind.    Iloriiliaut.     .\rcli.  f. 
I       niikr.  .\nat..  x.xxi.,  1888;   Ueber  Einstichstuberkulo.se.  Jena,  1S97. 
iSchujeninofif:  Veranderungen  d.    Haut    nach    Aetzungcn.     Beitr.    v.    Ziegler,   xxi., 
:        1S97. 

>snftleben:   Verschluss  der  Gefiisse  nach  der   Unterbindung.     Vircli.    .Vrch.,  77  Bd., 
'       1S79. 

/ermorel:   Rech.  sur  I'inflamm.  pleurale,  Paris,  1898. 
'iegler,  E.:   Entzimdung  der  serosen  Haute.     Beitr.  v.  Ziegler,  xxi.,  1897. 

6ee  also  §§94  and  95. 


IV.  Chronic  Inflammations. 

§  98.  Inflammation  is,  according  to  its  nature,  an  acute  process,  but 

various  conditions  may  cause  the  phenomena  of  tissue-def;eneration  and 

exudation  to  persi.st  for  a  longer 
time,  and  the  inflammation  be- 
comes clii'onic. 

The  causes  of  chronic  in- 
flammations may  be  fouiid,  in 
the  hrst  i)hice,  in  the  fact  that 
in  the  course  of  an  acute  infiain- 
mation  there  occur  chant/cs  ichich 
2)revent  a  rapid  healiny.  In  this 
sense,  as  may  be  deduced  from 
the  foregoing,  act  all  large  tis- 
sue defects  and  tissue  necroses, 
as  well  as  large  masses  of  exu- 
date which  are  with  difliculty 
ab.sorbable.  When  necrotic 
miisses  of  tissm^  are  not  com- 
l»lett'ly  ab.sorhahlc,  as  in  tlie  case 
of  largi!  ])ie('('s  of  bone,  they 
may  indeed  becomti  secpicstrat- 
ed,  but  ])ersist  as  secpicstra  for 
years  (Fig.  2.'n,  a),  and  keep  up 
a  constant  inflammation.  Fol- 
lowing! he  ])ro(ln<'li<)nof  a  large, 
suiMMlicial  defect  of  llie  skin  as 
a  lesnlt  of  a  burn,  lliere  devel- 
ops a  granulation  lissne,  but 
nionlhs  jnay  i>ass  belure  the 
wound   surface  is  conciciI   (t\t  t 

with  ei)ithelinm  fr«»ni  lli Iges 

and  the  pi-ocess  tlierel)y  brunghl 
Fig.  ;>3L. -Necrosis  of  fifteen  years'  duration  in  the  .],.<_„. 

jower  pan  of  the  ciiaphysis  of  the  femur,    a,  Seques-        lO  a  CIOS«  . 

I'-nini : /j,  c.  edges  of  the  opening  in  the  thickened  bone  A      fni-f  lu'i-    cause    of    rlii'onic 

jalcoholic  preparation) .    Reduced  one-third.  ^ 


366 


IXFLAMMATIOX, 


inflammation  is  found  in  con 
For  example,  the  frequently 
repeated  inhalation  of  dust 
may  cause  chronic  inflamma- 
tion of  the  lungs;  repeated 
rubbing  of  the  skin  may 
cause  a  chronic  inflammation 
of  the  part  affected;  patho- 
logical alterations  of  the 
stomach  contents  may  cause 
chronic  inflammation  of  tlu 
stomach.  In  the  canals  el 
the  body  in  which  concretions 
may  form,  the  latter  may 
give  rise  to  lasting  tissue- 
lesions. 

When  there  exist  in  a  tis- 
sue unfavorable  nutritive  con- 
ditions— i.e.,  marked  conges 
tion — these  may  enable  sliglil 
external  influences,  that  undo 
normal  conditions  either  j^ro- 
duce  no  inflammation  at  all 
or  one  soon  subsiding,  to  set 
up  ulcerative  processes  sho^\  - 
iug  no  tendency  to  heal.  In 
this  manner,  for  exainple, 
chronic  ulcers  of  the  leg  may 
arise. 

A  very  frequent  cause  of 
chronic  inflammation  is  fur- 
nished by  infections,  i>arti('u- 
larly  those  caused  by  bacteri(( 
and  moulds,  which  multiply  in 
the  body  and  thus  constantly 
give  rise  to  new  inflammatory 
irritation.  The  inflammations 
which  they  cause  are  distin- 
guished from  others  chielly 
Ijy  the  fact  that  they  lead  t'<  • 
connective  -  tissue  prolifera- 
tions {infectious  granulation 
tumors),  and  that  they  usmilly 
show  a  prof/ressire  character, 
and  foiiii  metastases  through 
the  lymph-  and  blood-vessels. 

Finally,  clironic  intoxica- 
tions form  a  last  cause.  These 
affect  chiefly  the  kidneys  and 
the  liver,  and  may  be  at- 
tributed either  to  the  con- 
tinued introduction  into  the 
organism  through  the  gastro- 
intestinal tract,  lungs,  or  skin 


stanthj   repeated  injnrtj  hy  external  inititences. 


k 


j; 


m 


' ,  t 


^  ) 


I  I  (II  I      I  1      r  I         I  f    1   1  pun 

Till  1(  II.   1  liiiu  iisMic   with   ^lui  I  III       ih      li     111  I  <  h  I 

fill     ^     111     th        IK  \\l\     f    MM      i  mi       I   \t     lIsslK         /      tl 

(.n((l  I  Ic  HI  I    (    luwiN   1   iiiinl   (    niuctUL  ti^-Mit    witli  i 
elistiL  IlbHs,  d,  {ri  null  itiun  tis'^ue  covered  witli  pus 

cloSiiii  hmiting  mcIUuraue  uf  thtj  pleura;  /,  elaouio  flbrv , 


CHRONIC    INFLAMMATION. 


307 


,  333.— Section  of  a  stonecutter's  lung  with  fibroid  nod- 
alcoliol,  i)i<Tocarinine).    a.  Group  of  llbrold  nodules; 

normallung  tissue;  c,  thickened  lung  tissue  still  containing 

nchi,  vessels,  and  a  few  alveoli.    X  9. 


i'  substancos  liannful   to  the  organs  directly  concornod  or  fo  olliors; 

r  injurious  snbstant'cs  may  be  produced  within  the  l)ody  itsell',  tlirough 

sturbances  of  the  i)rocesses  of  metabolism,  thus  ,ui\  iui;'  rise  to  ;i  clnotiir 

itoiiito.vicdiion. 
The  forms  of  chronic  inflammation  me  delenniiied  i);iitlv  by  their 

iiidaineiital  causes,  ])artly  by  the  character  ot'  the  alVected  tissue. 
Chronic    iiillanniiat  ions     characterized     especially    i)y    hyperplastic 

rmations  of  connective  tissue  are  I'omid  especially  in  the  ser- 
ous nuMubranes,  lungs,  and 
skin,  but  may  occur  also  in 
other  tis.sues.  Chronic 
pleuiilis,  caused  by  exu- 
dates which  are  with  ditli- 
culty  absoi'bable,  or  by 
chronic,  infections,  Iciid  to 
extensive  t<r(ir-lil:r  ihickcniiujH 
of  tJie pleura  (^V'\y[,.  232,  h,  c), 
the  new-formation  of  tissue 
occurring  in  part  \\\\o\\  the 
pleura  (c)  and  in  part  with- 
in it  (/>).  3Ioi'<M>ver,  indu- 
ration of  the  Jun(/  ((()  may 
follow  vai"ious  infectious  in- 
flammations, or  may  be 
caused  by  the  continued  in- 
halation of  stone  dust,  in  the 
latter  case  being  character- 
ized   by   the    formation    of 

)roid  nodules  (Fig.  I'.'J.S,  a),  in  part   also   by  diffuse   induration   (c). 

(utinued  irritation  in  the  neighborhood  of  the  orifices  of  the  urogenital 

»paratus,   as  through  the  discharge  of    irritating  seci-etions  Tchi-onic 

iiiorrha'a),   leads  frequently  to  the  foi-niation    of  pointed  eondi/lonuda 

ondytomaia  acuminata) — i.e.,  to  a  hypei-pl;isi;i  of  the  p:iitil!;e  and  epithe- 

iin,  in  Mliich  the   inflamed  _ 

id  infiltrated  papillai  grow 

It  with   tiieir  vessels   (Fig, 

'f,  a,  !>')  and  frequently  di- 

«le  into  bi'anches. 
Fre(|uently     repeated     or 

ntinned     slight     infiamnni- 

>ns  of    the   skin    and   sub- 

taneous  tissue,  due  to  me- 
lical  lesions,  parasites,  or 

iv  other  continued  irrita- 
n,  may  also,  if  they  leach 
consideiable    extent,    give 

^'  to  a  diffuse  hyperi)lasia 
connective  tissue,  which  is 

lown  as  elephantiasis. 
Inflaniniatoiy      prolifera- 

i>ns  of  the   periosteum  and 

Ine-marrow,  which  give  rise  to  pidlioloi/ieal   neir-form<dions  (f  tionc  o 

^I'ttperostosis  (Fig.  235).  may  be  caused  both  by  non-specitic  iri'ilat  ions- 

•T  example,  by  intlammations  which  run  their  course  in  the  neighbor 

t'od  of  chronic  ulcers — as  w^ell  as  by  specilic  infect  ion.s — for  example 

'philis  or  tuberculosis. 


Fig.  234.— Condyloma  aciiniinatum  (injected  preparation). 
a,  Enlarped  iiranchiiiK  papilhe;  /<,  epjdennls.     >:  at. 


368 


INFLAMMATION, 


Chronic  catarrhs  of  tlie  mucous  membraues  are  sometimes  caused  bv 
specific  iulVction  (gonorrhoea,  tuberculosis),  sometimes  by  uou-specifi< 
iujuries  (concretions,  pathological  changes  iu  the  gastric  or  intestina 
contents),  and  sometimes  by  continued  disturbances  of  circulation  (cou 
gestion). 

Chronic  abscesses  arise  usually  from  acute  abscesses,  and  have  th 
same  etiology  as  the  latter;  but  may  also  develop  more  gradually  and  ar; 
then  caused  by  special  infectious,  most  fre- 
quently tuberculosis  and  actinomycosis.  They 
are  usually  limited  externally  by  a  conuec- 
ti\  e-tissue  membrane  covered  with  granula- 
tion tissue,  and  may  increase  iu  siz-o  partly 
through  the  secretion  of  pus  from  the  ab- 
scess-wall, and  partly  through  the  destruction 
of  the  wall  and  the  neighboring  tissue.  Pro- 
gressive enlargement  toward  the  deep-lying 
parts  leads  to  the  formation  of  burrowing  or 
congestive  abscesses.  Their  increase  in  size 
is  always  to  be  ascribed  to  the  persistence  of 
the  infection.  Perforation  into  neighboring- 
tissues  leads  accordingly,  also,  to  new  infect- 
ive inflammations. 

The  tuberculous  and  actinomycotic  forms 
of  chronic  abscesses  are  distinguished  from 
other  forms  partly  by  the  specific  characteris- 
tics of  the  pus  and  partly  by  the  peculiar 
structure  of  the  abscess-membrane  (see  Tuber- 
culosis and  Actinomycosis,  Chapter  X.). 

Chronic  ulcers  are  caused  chiefly  by  spe- 
cific infections  (tuberculosis,  syphilis,  gland- 
ers), but  non-specific  injurious  agents  may 
lead  to  chronic  ulcerative  processes  in  tissues 
which  are  especially  susceptible  to  such 
changes.  Thus  chronic  congestion  in  the 
vessels  of  the  leg  may  have  such  an  effect 
that  ulcers  arising  through  any  mechanical 
influence  may  be  prevented  from  healing  un- 
der the  unusual  conditions  in  which  the  leg 
finds  itself.  Likewise  peculiar  qualities  of 
the  stomach  contents  may  hinder  the  healing 
of  an  ulcer  of  the  stomach.  If  healing  be- 
gins at  one  edge  of  an  ulcec-  while  the  ulcera- 
tion advances  at  other  parts,  there  arises  the 
form  of  ulcer  known  as  scrpif/inoKs.  The  ex- 
cessive development  of  granulation  tissue  in 
an  ulcer  leads  to  the  prodnction  of  an  ulcus  ' 

elevatum  hi/pert roph icum ;  a  dense  callous,  lardaceous  thickening  of  j© 
edge  and  base  gives  rise  to  the  form  known  as  ulcus  callosum,  or  indoM, 
or  (itoju'cum. 

Chronic  proliferations  of  granulation  tissue — i.e.,  f/ranuJationsm'h 
persist  as  suc/i  for  a  longer  or  shorter  time  without  becoming  changed  i  o 
connective  tissue — occur  chiefly  in  various  specific  infections,  the  1  >t 
known  being  tuberculosis,  sj/2}hilis,  leprosy,  glanders,  rkinoscleroma,  ■  ^ 
actinomycosis.     Since  the  granulations  iu  these  infectious  often  ftui 


Fig.  235,— Periosteal  hyperos  i3 
of  the  tibia,  at  tlie  base  of  a  otn  ie 
ulcer  of  the  leg.  Reduced  > 
fifths. 


VAHIKTIKS    OF    CIIHOMC    IXFLA.M  M  A'l'IOX.  'M'){\ 

jliiiijioid  i)rolit'er;it-ioiis  and  tuiu«»i-likt'  t(»iiii:it  ions,  llu-y  arc  (•Itcii  also 
LalU'd  fungous  granulations  orcaro  luxurians  and  infectious  granula- 
tion tumors  or  granulomata.  All  tlu'se  show  certain  peculiarities 
»\hii'h  enable  lis  to  recognize,  I'loni  tlie  strucluie,  origin,  and  life-history 


Fig.  236.— Section  till  m  itiopbu  Iii^'iMntestinc  (alcoliol,  aliim-cjinninc).    n,  (ilan- 

lular  layer  decreiised  tut  11.  u  i     i-  n  imu  in  i/lit ,  /<,  imiM  ularis  mucusii' ;  i,  subiuin-usii;  </,  musi-iilaris; 
total  atrophy  of  the  uiULo:5d     -^  oil 

if  tlie  oraniilation-formatioii,  also  its  specific  etiology  (see  .Chai)ter  X.). 
[I  should  be  noted,  however,  that  tlie  etiology  of  some  of  the  gianulo- 
uata  developing  in  the  skin  is  still  nnknown. 

Chronic  inflammations  iu  wliich  atrophy  of  the  specific  tissue  is 


Ma 


h^ 


-^>V 


-ol^ 


'<^/j^i'<^ 


e    a- 


Fir  2T  — Inrluntmn  nnrl  itrophv  r  f  th(  n  n  il  tls'-iir  fn  <  lir  rii    in  plirltis  ( il 
nirkfnpd  111(1  (Urn         |     jl       f   1        i      i      /     i    i      il     I   i     i  iil   i  \     -  l^         v 

\*  i>s  urt  in  jiirt  m  i  n  ii  1  \n  1  li  in  ti  ii  Mil  i  itl  li  i  f  i  tin  n  iii  i  |  irt  I  M  /  ("iii- 
*l'ttl>  <  hlittrit  1  Ll  II  nili>  h  in  Ji  ii  ii^  iii  i  -  >  f  (  iL'-iilili  n  irJsiiiL'  fr  in  t  xii  I  it<  in  I  <!' m|uii. 
'iitMl  tpiitK  Inn  111  stniu  1  with  niK  li  i  /  (l(  s  pi  ini  iti  d  nloiiMnilii  i  pin»  lliiin  (/  (upsnlar  <  p'thi-- 
ii'in  'i  <  Hi]-  1  nun  irv  tubule  with  atrophu  (pitlKlnim  i  c  oil  ipsi  d  tuhuU  without  <  pHht  Hum,  /i. 
M»rpitsti(   loiirit   ti\    tii^ne  •jtrom  I    /  cellular  fo(  i     /;i   nornul,  soni<  wh  it  (111  itcd  tiiiiiilis    n,  aIT»nnt 

!'-«<«  1     (I    \(  111  'M 

sssociatcil  Miih  hyperplasia  of  the  connective  tissue,  occiii-  jiailieiilaily 
n  the  mucous  membrane  of  the  gastro  iiit<'stiiial  tract,  and   in  the  kid- 
»eys  and  liver. 
L>4 


370 


INFLAMMATION, 


In  the  intestinal  canal  the  cause  may  lie  in  specific  (dysentery)  as  ' 
well  as  iu  uoii-specitic  irritations;  the  latter  being  dependent  upon  some 
abnormal  property  of  the  contents  of  the  canal.  The  epithelial  elemcDts 
may  undergo  necrosis  in  association  with  persistent  desquamation,  the 
connective  tissue  being  unaffected ;  or  they  may  necrose  and  disintegrate 
at  the  same  time  with  the  connective  tissue  upon  which  they  rest.  Thet 
final  result  is  a  mucous  membrane  (Fig.  236)  which  either  contains  nc 
glands  (e)  or  only  rudimentary  ones  {a). 

In  the  liver  and  kidneys  the  chronic  inflammations  which  lead  tc 
atrophy  and  induration,  and  whose  final  results  are  known  as  cirrhosii 
of  the  liver  and  indurated  contracted  kidney,  are  hfematogeuous  dis 
eases,  in  so  far  as  they  do  not  depend  upon  disturbances  in  the  effereu' 


'^^^'A  i^^  l-  ^ . 


tlL  ~..flfifj^**r    »     ""^ 


-X  \ 


?x. 


Fig.  238.— Connective-tissue  hyperplasia  and  proliferation  of  bile-ducts  in  chronic  hepatitis  (alcohf 
haematoxylin I .     a.o,.  Liver-lobules;   h,  hyperplastic  periportal  connective  tissue;   c,  old  bile-ducts: 
newly  formed  bile-ducts ;  f ,  foci  of  small-celled  infiltration.     X  55. 


passages  (obstruction,  inflammation  of  pelvis  of  kidney,  formation  e 
concretions),  and  are  caused  partly  by  hifections  and  partly  by  intoxia 
tiom.  They  may  begin  either  as  acute  inflammations  or  more  insidiously 
and  are  characterized  by  atrophy  and  degeneration  of  the  glandular  ti;! 
sue  (Fig.  237,  h,  i),  hyperplasia  of  the  connective  tissue  (Fig.  237,  a,  i 
and  Fig.  238,  6),  through  cellular  infiltration,  formation  of  granulatio 
tissue  (Fig.  237,  /,  and  Fig.  238,  e),  through  obliteration  of  old  vesse 
(Fig.  237,  c,  d),  and  through  the  formation  of  new  vessels.  In  the  liv( 
there  occurs  also  very  frequently  a  formation  of  new  bile-ducts  (Fi; 
238,  d),  which,  however,  for  the  greater  part  do  not  functionate. 


CHAPTER  VIII. 
Tumors. 

I.  General  Considerations. 

§  99.  A  neoplasm,  or  autonomous  new-growth,  atypical  blastoma 

r  tumor  in  tlie  narrower  sense,  is  ;i  ncic-J'ormaihni  of  H.snuc,  (ippannihj 
ristiif/  and  f/roiriiif/  indrpeudeutJi/,  having  an  atjiplral  structuir,  inserted 
srirxsh/  into  the  orf/ani.sin,  j>o.S'S('.S'.s'//<^  no  function  of  .service  to  the  body,  and 
\iowin(/  no  typical  termination  to  its  growth.  The  atypical  character  of  the 
i ructnre  of  a  tnmor  is  shown  in  its  external  appearance  as  Mell  as  in  its 
iiternal  oryanization  in  that  a  trne  tnnior  departs  more  or  less  in  stnict- 
ire  from  that  of  a  normal  organ.  Wlien  this  departnre  is  bnt  slight,  the 
ructure  of  the  tnmor  approaclies  closely  to  tliat  of  the  tissne-hypertro- 
hies;  and  there  oecnr  cases  in  which  the  diffeience  in  sli-uctiire  is  so 
ttle  that  it  becomes  ^•el•y  difticnlt  to  decide  whether  an  excessive  new- 
lowth  of  tissue  is  to  be  classed  as  a  tumor  or  a  hypertrophy. 
i  Tumors  may  develop  in  any  tissne  of  the  body  which  is  capable  of 
rowth,  and  arise  through  the  proliferation  of  the  tissue=cells,  asso- 
::ated  with  a  new=formation  of  blood=vessels.  Not  infiecpiently  there 
?ci\vs  A\mnn  emigration  of  lei(coci/tes  and  li/mphocj/fes  into  Uw  tnmor,  and 
Kudative  processes  and  inflammatory  tissne-proliferations  may  take 
ilace  in  its  neighborhood,  bnt  these  phenomena  form  jio  essential  part 
f  the  development  of  the  tnmor. 

The  processes  of  cell-division  and  new-formation  of  blood-vessels  are 
lie  Siime  as  those  described  in  §§  80  and  82 — i.e.,  the  division  of  the  cells 
iikes  place  by  karyomitosis,  and  the  new  vessels  are  formed  from  buds 
liven  off  by  the  proliferating  cells  of  the  walls  of  old  vessels.  The 
iiitoses  are  for  the  greater  i:»art  typical  (Fig.  239,  h),  bnt  tlu're  are  also 
i)und  relatively  often  atypical  forms,  snch  as  asymmetrical  di\isioiis, 
luclear  figures  with  abnormally  large  chromatin  masses  (s(»-call('d  giant 
Iiitoses),  pluripolar  mitoses,  and  forms  of  nuclear  fragmentation,  and 
liso  direct  segmentation, 

1  In  their  fully  developed  condition  tumors  are  for  the  greater  ])ait  well 
('fined  /Vo>«  the  surrounding  tissues,  but  in  some  cases  they  may  pass  into  the 
nghhoring  tissue  without  any  sharply  defined  border  of  transition.  Further, 
n  entire  organ  may  become  transformed  into  a  tumor,  or  large  portions  of 
'Hsue  not  sharply  outlined  from  their  surroundings  may  take  on  the  character 
f  atumor.  Through  the  disintegration  of  tumor  tissue  there  very  fre- 
luently  arise  idcers. 

The  difference  between  the  structure  of  a  tumor  and  that  of  noiinal 
ssue  is  usually  recognizable  even  macroscopically,  but  thei-e  are  also 
imors  which  so  closely  resemble  the  parent  tissue  from  wliich  theyai-ise 
lat  the  difference  can"^  be  made  out  only  thiough  a  more  careful  exami- 
ation. 

j  The  circumscribed  tumors  are,  usually /(or/M7«/- (Figs.  24(»,  '/ ;  -'12.  <l.  <  -. 
1-13,  a).     The  size  of  the  single  nodules  varies,  according  to  tli.-  kind  of 

371 


372 


TUMORS, 


tumor  and  the  stage  of  development  at  the  time  of  examination,  from  tlie 
smallest  visible  miliary  and  submiliary  nodules  to  masses  weighing  ten  tc 
twenty  kilograms  or  more.  When  situated  upon  the  surface  of  an  organ 
nodular  tumors  not  infrequently  take  on  the  form  of  a  sponge  (Fig.  240. 
d)  or  of  a  polyp,  and  are  accordingly  designated /ww^o/tZ  or  polypoid  tii 
mors.  "When  a  new-growth  on  the  surface  of  a  mucous  membrane  or  tin 
skin  leads  to  an  enlargement  and  branching  of  the  papilla?  there  present 
or  if  new  jjapilhe  are  formed,  there  arise  warty,  verrucose,  and  papUlari 
tumors  or  papillomcda  (Fig.  241).  A  further  development  of  the  i)apillarii 
structure  may  lead  to  a  dendritic  branching  and  the  formation  of  a  catdi 
Jiower  mass. 

Tumors  usually  develoi)  from  small  beginnings;  only  rarely  do  the; 
arise  from  centres  extending  diffusely  throughout  an  entire  organ.     Thei 


Fig.  2.39.— Tissue  from  a  carcinoma  of  the  breast,  containing  numerous  division-flffures  in  different  pha 
of  mitosis  (Flemming's  solution,  safranin).    a,  Stroma ;  b,  epithelial  plugs.    X  5(10.  ^ 


growth  may  be  either  rapid  or  slow,  and  with  occasional  periods  of  qij 
escence.  Their  growth  may  be  suspended  for  years,  and  then  sudden; 
again  they  iK'Come  active. 

The  structure  of  the  tumor  is  determined  by  the  parent  tissue  fn 
which  it  taJces  its  origin  ;  and  although  the  true  tumors  always  show  a  C( 
tain  atypical  character,  they  yet  retain  certain  characteristics  of  the  p: 
tissue. 

According  to  their  stnictiiie  and  genesis  tumors  may  be  divided  ii  • 
three  groups:  1,  co)inertice-tissuc  tumors;  2,  epithelial  tumors;  3,  teraU^ 
tumors  and  cysts.  It  shoukl  l)e  noted,  howcAcr,  that  there  are  many  for« 
of  tumors  which,  according  to  the  point  of  view,  may  be  classed  as  if 
longing  to  two,  or  even  1o  all  three  groups. 

The  connective=tissue  tumors  or  the  tumors  arising  from  the  sf 
porting=tissue  substances,  and  which  are  often  called  histoid  tumors,  a- 
sisl  of  tissues  which  in  their  structure  correspond  in  part  to  mature  all 
in  part  to  eml)ryonal  connective  tissue  of  the  mesoderm,  and  moreo^jr 
take  tlieir  origin  from  mesodermal  connective  tissues.     Ordinarily  th 


GENERAL    COXSIDEHA TIOXS    KK(;  AHDI  .\(;    TIMOHS. 


(lie  also  iiK'liuled  in  this  group  Uioso  tumors  arisin<;  from  11 
i^pecilic  elements  of  the  nervous  system,  the  iilia-eells  and  uaniilini 
ells,    : 


muscle-tumors,    since 


.     Illc 


lliese     in     tlicii 
moie    than    tli 
epithelial. 

The  (lilferences  in 
the  types  of  the;  con- 
nect i\e  -  tissue  tumoi's 
are  essentially  depen- 
dent upon  the  charac- 
ter of  the  grouud-sub- 
stance,  and  in  part  also 
upon  the  cells.  AVhen 
the  tumors  aie  very 
rich  in  cells  and  the 
jiiouud  -  substance  but 
s  1  i  o-  li  1 1  y  developed, 
they  acquire  a  soft  con- 
sistency and  are  classed 
with  the  Hurcomata. 
Yeiy  soft  foi-ms  are 
^  f    ^  ^^  designated  as  i»<'r/»<7rn7/ 

If    \  ^%-^^   ^ii--^*'''''**^         -'  *^^'    f'i'ff/'    mrdidlareH. 

4  '     ^^b-^^"  T  "fc^^*^^^       J    -  Through  the  cojubiua- 

'.^  ^St^  -^^c.^^  ^         .,  ^I^jj^  r^  different  forms 

of  connective  tissue 
theie  arise  mixed  con- 
nect irr-t  issue  fidjiors. 

The  epithelial  tu  = 
mors  are  composed  of 
cells  derived  from  sur- 

'ace  epithelium  or  from  f/Jand-ceUs,  and  also  of  vaseidar  roiniecfire  tissue — 
hich  forms  a  supporting  framework  in  the  spaces  of  which  tlie  cells 

[rising  from  the  proliferation  of  surface  epithelium  or  gland-cells  lie  in 

Letinite  groups.     Inasmuch  as  this  arrangement  gives  to  the-tuuujrsa 

Itructure  suggesting  that  of  a  gland,  they  are  often  also  called  organoid 

nuiors,  in  coutradistinctiou  to  the  histoid  connective-tissue  tumor.s.     It 

iliould  be  noted,  however,  that  there  are  also  included  in  the  couuec- 

jive-tissue  group  of  tumors  certain 

I'arieties     (endotheliomata)     which. 

bve  an  organoid  structure. 

1    The  cells  which  give  the  epithe- 

jial  tumors  their  especial  character 

rise  either  from  the  ectoderm  oi-  en- 

ioderm,  and  from  the  glands  devel- 

Iping  fiom  the  same,  or  finally  from 

he   niesoch'rmal    ei)itheliuni    of   the 

pericardium,  and  of  the  i)leural  and 

.•eritoneal  cavities,  or  of  the  glands 

rising    from    this    layer    (kidneys, 

exual   glands,    adrenals).      Tumois 

javiiig  the  last-named  origin  often 

|how  more  or  less  distinctly  the  espec 


Fig.  310.  -Fungoid  carcinoma  of  the  endometrium  of  the  posterior 
all  of  the  uterus,  a.  Body  of  the  uterus;  ft,  cervix;  c,  vagina;  rt, 
imor.    Two-thirds  natural  size. 


.'41.- 1'; 


.f    th 


1   charactei 
Very  soft  cellular  epithelial  tumors  are  also  designated 


irom  which  tliev  arise. 


I   ..f  ii'clutii.      Nut 

l»arent  tissue 
III  (liilhiijj. 


374  TUMORS. 

Combinations  of  epithelial  proliferations  M'ith  proliferations  of  tb 
connective  tissne,  whicli  exceed  the  ordinary  amonut  of  snpporting  ti; 
sue  or  bear  a  sarcomatous  character,  lead  to  the  formation  of  eplthelh 
mixed  tionors. 

The  teratoid  tumors  and  cysts  form  a  group  which  is  especiall; 
characterized  on  the  one  hand  by  the  fact  that  they  contain  the  mo;,: 
A-aried  kinds  of  tissue  which  may  be  derived  from  all  three  germ-laye.'! 
(teratoid  mixed  tionors),  and  on  the  other  hand  by  the  presence  of  tissi 
formations  ia  regions  where  they  do  not  normally  occur.  Tumors,  ther* 
fore,  which  according  to  their  structure  maybe  placed  in  one  of  the  othc. 
groups,  may  be  considered  as  teratomata  on  account  of  their  situatio] 
Further,  there  are  also  included  in  the  group  of  teratoid  tumors  certa ' 
formations  which  according  to  their  structure,  origin,  and  j^hysiologic i 
relations  ought  not  to  be  classed  with  the  tumors.  ' 

Tumors  usually  develop  singly ;  but  it  also  happens  that  M'ithin , 
certain  tissue  system  there  may  appear  either  coincidently  or  in  succe; 
sion  a  great  number  of  tumors  of  the  same  kind,  so  that  it  must  li 
assumed  that  the  conOitions  requisite  for  the  development  of  these  t| 
mors  Mere  present  in  different  parts  of  the  system  affected.  At  tim; 
there  develop  in  different  organs  of  the  same  individual  two  entirely  d 
ferent  varieties  of  tumors,  which  stand  in  no  relation  to  each  other,  a^l. 
whose  coincident  appearance  is  purely  accidental,  ' 

I 

The  exact  determinatiou  of  wliat  sliould  be  inchided  under  the  term  tumoiji 
hardly  possible ;  and  consequently  the  designation  tumor  is  applied  to  many  differ.:!; 
formations  which,  according  to  their  etiology,  genesis,  and  life-characteristics,  have  i|d 
the  same  siguiticance.  The  idea  of  tumor  is,  therefore,  veiy  differently  conceived  K 
different  authors.  I  regard  it  as  advisable,  and  also  as  based  upon  the  life-characte j- 
tics  of  the  tissue-formations  which  we  are  about  to  consider,  to  exclude  in  the  first  pie 
from  the  class  of  tumors  all  hyperplastic  proliferations,  and  further  all  retention-cjS 
which  arise  purely  through  the  retention  of  secretions  and  show  no  independent  nfi- 
formation  of  tissue.  Further,  according  to  my  view,  there  sJiould  he  separated  from  ;« 
true  tumors  all  proliferations  of  tissue  due  to  the  pi'esence  of  parasites  or  to  infection,  \'- 
ticularly  the  infectious  granulomata  which  occur  in  tuberculosis,  syphilis,  leprosy,  i^. 
Should  it  be  proved — which  so  far  has  not  been  done — that  some  of  the  ue\v-gro\v;s 
now  included  with  the  true  tumors  are  caused  by  Infection,  they  should  also  be  ;- 
eluded  from  the  category  of  true  tumors.  j 

The  above  classification  of  tumors  is  based  essentially  upon  their  histolog^l 
character  and  histogenesis.  They  may  of  course  be  classified  according  to  other  po;;8 
of  view.  Lubarsch  has  offered  the  following  classification  with  reference  to  the  gro  |h 
and  behavior  of  the  tumor:  (1)  Tumors  which  differ  from  the  parent  tissue  in  jie 
arrangement  of  their  elements,  but  for  the  chief  part  present  no  recognizable  incriw 
or  at  most  only  a  transitory  growth  (various  teratoid  new-growths,  misplaced  tis'ie 
anlage,  congenital  na;vi,  many  adenomata,  myomata,  fibromata,  lipomata,  chonp- 
mata,  and  osteomata);  (2)  tumors  which  show  a  certain  autonomy  and  independenc  jJi 
their  structure,  but  yet  on  the  whole  obey  the  normal  laws  of  life  in  that  they  alv/s 
respect  the  physiological  tissue  boundaries  (myomata,  adenomata,  angiomata,  lipoma  1); 
(3)  tumors  winch  am  wholly  emancipated  from  the  physiological  laws  of  life  and  ;le 
in  the  tissues  in  total  lawlessness  of  growth  (carcinoma,  sarcoma).  j 

The  atypical  structure  of  tumors  is  not  given  so  much  prominence  by  allu- 
thors  as  has  been  dduc  above.  This  is  particularly  true  with  reference  to  those  tui'rs 
which  are  similar  in  structure  to  the  parent  tissue  from  which  the}'  arise,  and  whicl'Te 
accordingly  designated  homoplastic  tumors.  It  should  be  noted,  however,  that  evijin 
these  tumors,  in  "so  far  as  they  represent  true  neoplasms  (chondroma,  osteoma,  fibr  ia, 
etc.),  there  occur  in  general,  in  the  histological  structure,  coarser  oiganization,'o«i 
external  form,  pronounced  departures  from  the  normal.  Tumor-like  congenita' -is- 
sue-hypertrophies (for  example,  many  osteomata),  as  well  as  hyperplastic  newpr- 
mations  of  tissue  resulting  from  inflammatory  processes,  must  be  separated  froEilie 
true  tumors.  \ 

Tumors  are  in  no  sense  useful  to  the  organism  as  many  tissue-hypertro  iies 
may  be.     Tumor-tissue  does  not  possess  the  specific  activity  of  that  tissue  from  vl^h 


DEVELOPMENT    OF    TIM01{S.  87") 

it  springs,  so  that  tumors  can  in  noway  lu-  rcirardcd  as  useful  new  format  inns  of  tissue. 
It  happens,  intieeil,  that  in  certain  tumors  tliere  occur  processes  of  secretion  wliidi 
correspouti  to  normal  secretions— thus,  epithelial  tumors  may  produce  mucous  or  hornv 
or  colloid  material  (thyroid  tumors),  or  bile-pigment  (liver-tumors),  even  in  metastatic 
nodules— but  from  these  facts  we  can  conchulc  only  that,  in  manv  tumors  which  do  not 
differ  too  greatly  in  structure  from  the  parent  ti.ssuV,  the  cells  may  retain,  to  a  cj-rlain 
degree,  for  a  number  of  generations,  the  functional  capacities  of  the  parent  tissue. 
There  is,  however,  no  basis  for  believing  that  new  useful  tissue  is  formed  as  in  the  case; 
of  hypertrophy  from  increased  labor;  the  products  are  for  the  chief  i)art  of  uo  u.se  to 
the  liu.ly.  and  though  pi'rhaps  in  especial  cases  the  ioiline-coniauuiig  toiloid  produced 
by  n\alignant  tumors  of  the  thyroid  may  be  made  use  of.  such  a  fuiK  tiou  u.ust  surely 
be  of  nuicli  less  value  than  that  of  the  normal  tissu.-. 

The  tumors  arising  from  the  mesoderma!  epithelium  of  the  senms  mcmiiranea  or  of 
the  glands  arising  from  these  are  included  in  the  group  of  epithelial  tumors.  This  is 
justttied  by  the  fact  that  such  tumors  correspond  in  their  structure  and  clinical  be- 
havior to  tile  epithelial  tumors  of  the  ccto-  and  entoderm.  I  have  al.so  considered  the 
question  whether  it  would  not  be  advisable  (as  IlanKdiutnn  has  proposed)  to  class  also 
among  the  epithelial  tumors — i.e.,  the  adenomata  and  careinomata — those  tumors  which 
have  a  framework  of  connective  tissue,  the  spaces  of  which  are  tilled,  in  a  manner  sug- 
gesting epithelial  tissues,  with  cell  nests  arising  from  the  jtroliferating  endothelium  of 
the  blood-  and  lymph-vessels.  Aside  from  the  similarity  in  the  structure  of  these  t  umors 
with  the  ordinary  adenomata  and  careinomata,  there  may  be  taken  in  favor  of  this  view 
the  fact  that  from  the  anatomical  side  the  endothelium  of  the  blood-  and  lymph-vessels 
is  often  designated  as  mesodermal  epithelium.  Against  such  a  grouping'of  the  endo- 
thelial with  the  epithelial  tumors  may  be  urged  the  facts  that,  aside  from  the  general 
acceptance  of  the  term  endothelioma,  the  behavior  of  the  endothelium  of  the  blood-  and 
lymph-vessels  under  pathological  conditions  is  very  different  from  that  of  epithelium, 
and  that  in  many  tumors  it  is  impossible  to  separate  the  products  of  the  growth  of  the 
endothelium  of  the  blood-  and  lymph-vessels  from  the  products  of  proliferation  of  con- 
nective-tissue cells. 

Literature. 

(Development  of  Tumors.) 

Adami:  (Classification  of  Tumors.)     Jour,  of  Path,  and  Bact.,  1002. 

Alberts:   Das  Carcinom,  Jena,  1SS7. 

Albrecht:   Physiolos.  Funktionen  in  Geschwiilsten.     Miuich.  med.  Woch.,  1902. 

Aoyoma:  Indirecte  Kerntheilung  in  verschiedenen  Neubildungen.  Virch.  Arch.,  lOH 
Bd..  1886. 

Arnold:  Kerntheilungen  in  den  Zellen  der  Geschwiilste.  Virch.  Arch..  78  Bd.;  Kern- 
theilung und  vielkernige  Zellen.     lb.,  98  Bd.,  1884. 

Bard:  Anatomie  pathol.  generale  des  tumeurs.  Arch,  de  phys..  v..  1S8.");  iMuhrvologie 
<1.  (ieschwiilste.     C.  f.  a.  P.,  xiv.,  1903. 

Borst:    Die  Lehre  v.  d.  Geschwiilsten,  Wiesbaden,  1902. 

Brault:   Des  tumeurs.     Man.  d'hist.  path,  de  Cornil  et  Ranvier,  i.,  1901. 

Bucher;    .Multiple  Carcinome.     Beitr.  v.  Ziegler,  xiv.,  189)^. 

Casper:   Geschwiilste  bei  Thieren.     Ergebn.  d.  all.  Path.,  iii.,  1898,  u.  Wiesbaden.  1.S99. 

Cornil:  Division  indirecte  des  noyaux  et  des  cell,  dans  les  tumeurs.  Arch,  de  phys., 
ISSO. 

Hansemann:  Asymmetrische  Zelltheilung  in  Kpithelkreb.sen.  Virch.  Arch.,  110  Bd., 
1890;  Pathologische  Mitosen.  lb.,  12.i  Bd..  1891;  Die  Anaplasie  der  Geschwulst- 
zellen  u.  die  asymmetrischon  Mitosen.  lb..  129  Btl.,  1892;  Die  mikrosk.  Diagno.se 
der  f Ieschwiilste,  Berlin,  1902;  Gleichzeit.  York,  verschiedenart.  Geschwiilste.  Z.  f. 
Krel,sforsch.,i.,  1904. 

van  Heukelom:  Sarkome  u.  plastische  Entziindung.     Virch.  Arch..  107  Bd.,  INN?. 

Kaufmann:   .Multiplicitiit  d.  prim.  Carcinoms.     Virch.  Arch.,  7')  Bd..  1878. 

Klebs:  Aligeni.  ijathol.  Morphologic,  Jena,  1889. 

Lannois  et  Courmont:    Deux  cancers  primit.  du  tube  digestif.     Rev.  de  med.,    1894. 

Lubarsch:  Hyperf)lasie  u.  Geschwiilste.  p]rgebn.  d.  allg.  path.  Morph.,  Wiesbaden, 
189.5;  Zur  Lehre  v.  d.  Geschwulsten,  Wiesbaden,  1899;  Geschwiilste,  Ergob.  d.  a. 
P.,  vi.,  1901  (Lit.). 

Marchand:  Bezieh.  d.  path.  Anat.  z.  Entwickelungsgcsch.  Verh.  <i.  Deut.  p.ith. 
<^''cs..  ii.,  Berlin,  1900;  Gewebswucherung  u.  Geschwulstbildum:.  1).  med.  W'ocii., 
19(12. 

Muller:  Cellulare  Vorgange  in  Geschwiilsten.     Virch.  Arch.,  I'M)  Bd..  1892. 

Miiller,  J,:   Leber  den  feineren  Bau  und  die  Formen  der  krankh.  Geschwiilste,  18H:1. 

Paget:  Lectures  on  Tumors,  1852. 


376  TUMORS. 

Petrone:    Breve  guida  alio  studio  dei  tumori,  Catania,  1S90. 

Ribbert:    Gescliwulstlehre.  Bonn,  1904. 

Schimmelbusch:  ^Multiples   Auftreten    prim.    Carcinoma.     Langenbeck's   Arch.,  31 

Bd..  1889. 
Sciiniidt:   SecretionsA'crgange  in  Krebsen.     Virch.  Arch.,  148  Bd.,  1897  (Lit.). 
Senn:    Pathology  and  Surgical  Treatment  of  Tumors,  1895. 
Strobe:  Kerntheilung  und  Riesenzellenbildung  in  Geschwiilsten.      Beitr.  v.  Ziegler 

vii.,  1890;    Cellulare  Vorgange  u.  Erscheinungen  in  Geschwiilsten.     lb.,  xi..  1891 

Neuere  Arbeiten  iiber  Ilistogenese  u.   Aetiologie  des  Carcinoms.      Cbl.   f.  allg 

Path.,  ii.,  1891. 
Thiersch:  Der  Epithelkrebs  der  ausseren  Haut,  1865. 

Trambujsti:  Bau  u.  Theilung  der  Sarkomzellen.     Beitr.  v.  Ziegler,  xxii.,  1897. 
Vii'chow:  Die  krankhaften  Geschwiilste,  i.-iii.,  1863-67. 
Wells:   Multiple  Primary  Tumors.     Jour.  Path,  and  Bact..  1900  (Lit.). 
White:    The  Definition,  Term.inology,  and  Classification  of  Tumors.     Jour,  of  Path, 

vi.,  1899;    Pathogenesis  of  Tumors.     J.  of  Path.,  vii.,  1901. 
Williams:  The  Principles  of  Cancer  and  Tumor  Fom-iation,  London,  1889. 
Wilms:   Die  Mischgeschwiilste,  i.,  ii.,  Leipzig,  1899,  1900. 

See  also  §§  100  and  101. 


§  100.  The  etiology  of  tumors  is  by  no  means  uniform,  and  verj 
often  cannot  be  determined  with  certainty.  In  the  majority  of  cases! 
however,  the  conditions,  at  least,  under  which  the  new-growth  appeare< 
can  be  assigned  and  we  may  accordingly  establish  different  groups  o; 
tumors.  Infection  is  indeed  very  frequently  advanced  as  a  cause  of  tin 
mors,  but  such  etiology  has  not  in  any  case  been  demonstrated  beyom' 
doubt. 

As  the  first  grouj)  of  tumors,  according  to  etiology,  may  be  taken  thos. 
arising  from  especial  congenital  anlage,  so  that  we  may  in  a  certain  sensj 
regard  them  as  local  malformations  of  tissue.  They  develop  either  ii 
uterine  life,  and  are  present  at  birth,  or  later  in  extra-uterine  life,  dui; 
ing  the  period  of  growth  or  even  later,  in  which  case  trauma  not  iufrd 
quently  gives  the  immediate  occasion  for  the  beginning  of  the  develoji 
ment  of  the  tumor  from  the  preexisting  anlage.  ■ 

To  this  group  belong  in  the  first  place  many  osteomata,  chondromatr 
angiomata,  gliomata,  fibromata  (of  the  nerves  and  skin),  sarcomata  au; 
adenomata.  Further,  many  teratoid  tumors  and  cysts  are  also  to  tl 
included  in  this  group,  inasmuch  as  they  represent  in  part  either  r(| 
mains  of  foetal  structures,  transpositions  or  monogerminal  inclusions  (. 
embryonic  tissue,  implantations  of  rudimentary  portions  of  a  twin  en, 
bryo  (bigerminal  implantations),  or  probably  also  the  results  of  disturl, 
auces  of  the  earliest  stages  of  the  development  of  the  ovum.  ' 

A  second  group  develops  after  traumatic  injuries  of  the  tissves ;  audit  h:! 
been  reckoned  that  in  about  seven  to  fourteen  per  cent  of  cases  a  trai; 
matic  origin  can  be  assigned ;  particularly  in  the  case  of  sarcoma,  carcj 
noma,  and  osteoma.  The  causes  of  the  tumor-formation  may  be  a  singj 
injury,  a  stab,  a  blow,  crushing,  fracture,  etc.,  as  well  as  repeated  lUj 
chanical  irritation,  such  as  rubbing,  scratching,  etc.  • 

In  a  third  group  the  development  of  the  tumor  folloics  infiammation,  pm 
tieularly  the  formation  of  granulation  tissue  tcith  subsequent  cicatrization.  Tlj 
infiammation  and  ulceration  may  be  caused  by  non-specific  as  well  as  I 
specific  injurious  agents.  For  example,  cancer  of  the  gall-bladder  (Fil; 
242,  d,  e)  almost  invariably  develops  only  in  gall-bladders  which  coutai 
stones,  and  are  consequently  the  seat  of  clironic  inflammation, 
the  stomacli,  cancer  may  develop  in  the  edge  of  an  ulcer  or  in  the  resU; 
ing  scar  and  also  in  a  mucous  membrane  which  has  suftered  severe  chaug; 
as  the  i-esult  of  previous  infiammation.  In  the  external  skin  and  also  [ 
the  mucous  membranes  of  the  pharynx  and  larynx  cancers  occasional 


I 


ETIOLOGY    OF    TIMOHS. 


377 


irise  ill  the  baso  of  ii  tulxM'culous  (tr  s\  ]iliilil  ic  Ltianiiloiiia  or  in   llic  sc;ir 
if  such  a  i>i-(>('ess. 

Jn  a  fourth   ifroup  the  dcrcloptncnt  of  tin-  lionors  (tpixius  to  oirr  its  tnit/iii 


Fig.  St3. —Primary  carcinoma  of  the  gall-bladder  enclosing  an  impacted  gall-stone.  Frontal  section 
brougta  the  gall-bladder  and  liver.  «,  Liver;  /),  duodenum  ;  c,  gall-stone ;  <?,  wall  of  tlic  caninoiuatous 
all-bladder;  e,  cancerous  infiltration  of  the  neighboring  liver  tissue;  /,  portion  of  duodenum  which  is  In- 
Itrated  with  cancer  and  adherent  to  the  gall-bladder  tumor.    Natural  size. 

0  an  imequal  atrophy  of  the  elements  wlrkh  muTx-e  vp  a  tissue,  so  that  certain 
\indrances  to  f/roicth  are  removed  or  lessened.  Kot.  iiu'chanical  resist ;lIK'«^ 
ilone,  Imt  iiitiueiiees  dependent  u|)on  the  eheinieal  eonditions  of  the  tis- 
iiie,  should  l)e  considered  in  this  conneetion.  Here  l»('h»n,u-esi)e<'ially  cer- 
ain  epithrlidi  proliferations  (eanerrs)  whicli  th-xeloj)  in  (»ld  aj^r,  or  in 
M-jjaiis  whieh  after  a  ])eiiod  of  increased  activity  l)econie  atrophic.  In 
his  way,  for  example,  the  development  of  cancer  of  the  skin  may  lie 
ixplained  on  the  ground  that  the  connective  tissue  of  the  skin  nnderjiot's 

1  certain  retrooression  leading  to  a,  relaxation  of  its  structur*',  while  the 
■pithelium  is  still  possessed  of  its  full  power  of  prolifei'ation.  At  the 
anie  time  the  chemical  c,<miposition  of  tlie  connective  ti.ssue  m:iy  he 
Itered. 

It  cannot  bo  doubted  that  the  etiology  of  tumors  is  not  always  Ihi-  same,  us  is 
hown  by  the  variety  of  conditions  tmder  which  tiiey  arise. 

It  is  difflcult  to  sav  what  is  tiie  nature  of  llie  inlhience  wliich  excites  tlic  cells  to 
he  production  of  an  ahipiad  tinme.  Wc  aie  at  lirst  inclined  to  think  of  tiie  .same  causes 
khich  underlie  liypertropliy  and  regeneration  of  tissue,  also,  on  the  one  liand,  of  «'spe- 
ial  congenital  aiilage  or  of  stimuli  wliich  increase  the  formative  activity  of  the  cells. 


378  TUMORS. 

and  on  the  other  hand,  of  a  lessening  or  removal  of  hindrances  to  growth.  But  it  sti 
remains  a  problem  why  there  should  not  be  formed  typical  tissues  which  would  so  fi 
into  the  organization  of  the  body  that  they  would  be  of  service  to  the  latter.  In  th 
attempt  to  explain  this  phenomenon,  Avhich  is  at  the  same  time  associated  with  an  ir 
crease  in  the  vital  and  reproductive  capacities  of  the  cells,  even  under  pathological  cor 
ditions  (metastasis  of  the  cells  through  the  blood-  and  lymph-vessels),  many  writei 
liave  sought  and  would  recognize  as  tlie  cause  the  presence  of  par((sites  (see  Etiolog 
of  Carcinoma) ;  but  our  present  knowledge  does  not  in  any  way  justify  us  in  attributin: 
the  development  of  true  tumors,  of  autonomous  new-growths,  to  the  influence  of  pan 
sites.  On  the  contrary,  the  development  and  life-history  of  tumors,  and  in  partuiil; 
the  formation  of  metastases,  which  without  doubt  arise  througli  the  multiplication  ( 
living  tumor-cells  transported  in  the  lymph-  or  blood-stream,  speak  against  the  hyjiotl 
esis  of  the  parasitic  nature  of  tumors. 

Cohnlici'm  advanced  the  theory  that  all  true  tumors  arose  from  especial  tumn 
anlage  which  had  their  origin  in  the  persistence  of  foci  of  embryonal  tissue.  Xcith 
the  results  of  clinical  observation  nor  of  the  anatomical  investigation  of  the  tissu 
speak  in  favor  of  such  a  theory. 

Ribhei't  is  of  the  opinicm  that  the  cause  of  the  pathological  proliferation  Avhich  leai 
to  tumor  formation  is  to  be  found  particularly  in  a  separation  of  cells  or  cell-grou), 
from  their  organic  relations,  such  a  separation  occurring  either  as  the  result  of  iutr; 
uterine  disturbances  of  development  or  later  under  the  influence  of  external  agencic' 
Nevertheless,  such  transplantations  or  separations  of  cell-groups  take  place  very  fi| 
quentl}^  in  intra-viterine  life,  or  after  trauma,  after  ulceration,  in  scars  and  in  infectio ' 
granulomata,  Avithout  any  subsequent  development  of  a  tumor.  These  transphud 
tions  of  tissue  constitute  only  one  of  the  predisposing  causes  of  tumorformation,  but  soi 
other  factor  is  necessary  to  excite  the  atypical  progressive  tissue-proliferation — i.e.,  t 
development  of  the  tumor.  The  development  of  a  tumor  is,  therefore,  in  no  icise  depei 
dentupon  a  transplantation  of  tissue  ;  nither  does  the  tumor-proliferation  take  its  origin  > 
cells  which  are  normally  situated ;  and  this  may  be  actually  demonstrated,  particulai' 
in  the  case  of  epithelial  tumors. 

Beard  holds  the  view  that  tumors,  in  particular  the  carcinomata,  arise  from  scxi 
cells  which,  during  the  development  of  the  body,  have  been  displaced  between  the  ;; 
matic  cells  and  are  there  preserved.  ! 

Our  knowledge  of  the  causes  of  tuvior-development  at  the  present  time  may  be  suminj 
up  as  follows:  Inherited  and  acquired  conditions  of  certain  cells  and  cell-groups,  whij 
assert  themselves  in  a  tendency  to  increased  formative  activity  with  the  production^' 
atypical  tissue,  lead  to  the  formation  of  tumors.  In  many  cases  this  proliferatiorj! 
prepared  for,  favored,  and  excited  by  the  transplantation  of  cells  and  cell-groups,  li- 
often  also  through  changes  in  the  neighborhood  of  the  cells  concerned.  No  gent',1 
scheme  applicable  to  the  development  of  all  tumors  can  be  given.  On  the  contra; 
the  conditions  vary  not  only  wMth  the  different  forms  of  tumors,  but  also  with  the  ic.'- 
vidual  cases  of  the  same  tumor-type.  Moreover,  it  should  not  be  forgotten  that  'p 
formations  which  we  class  as  tumors  do  not  all  possess  the  same  significance,  and  t  J 
many  of  the  same  ought  more  properly  to  be  classed  with  other  phenomena  of  gro\fi 
(malformations).  '' 

Literature. 

{Etiology  and  Genesis  of  Tumors. )  ' 

Adami:  On  Growth  and  Overgrowth,  etc.  Med.  Chron.,  1900;  Concerning  the  Cau- 
tion of  Cancerous  and  Other  New-Growths.     Yale  Med.  Jour.,  1901. 

Askanazy:  Geschwulste  d.  in  d.  Niere  eingeschloss.  Nebenniereukeime.  Beitr  '. 
Ziegler,  xiv.,  1893. 

Beneke:  Ne\iere  Arbeiten  z.  Lehre  vom  Carcinom.  Schmidt's  Jahrb.,  234  Bd.,  If!; 
Ganalioiieurom.    Beitr.  v.   Ziea-ler,   xxx.,  1901. 

Bogehold:  Entwickelung  von  malignen  Tumoren  aus  Narben.  Yirch.  Arch.,  88  V-, 
1SS2.  ; 

Boll:  Das  Princip  das  Wachsthums,  Berlin,  1876. 

Bonnet:  Zur  Aetiologie  der  Embryonic.     Mon.  f.  Gebh.,  1901. 

Borsch:  Pathogenese  d.  malignen  Geschwulste.     Virch.  Arch.,  162  Bd.,  1900. 

Buxton:  Enzymes  in  Tumors.     Jour,  of  Med.  Res.,  1903. 

Cohnheim:  Vorlesungen  liber  allgemeine  Pathologic,  Berlin,  1882. 

Crone:  Lupuscarcinom  des  Kehlkopfs.    Arb.  a.  d.  path.  Inst.  v.  Baumgarten,  ii.,  1  *• 

Ozerny:  Warum  diirfen  wir  die  parasit.  Theorie  fiir  die  bosart.  Geschwulste  i)-»t 
aufgeben?    Beitr.  v.  Bruns,  xxv.,  1899. 

Foa:   Sui  parassiti  et  sulla  istologia  patologica  del  cancro.     Arch,   per  le  So.  JMU 


ETIOLOGY    AND    GENESIS    OF   Tl'MOliS.  ;;79 

Haberern:  Datcii /ur  Lcliro  von  den  Ciillusiuinorcn.     Ljinircnbt'ck's  Aicli.,    -1:5  Bd  , 

Hansemann:  Speciticitiit,  Altrnisnuis  u.  Anaplusic  dcr   ZcIIimi,   l^fiiin,  1S<J3. 
Hauser;  Das   cluon.   .Mauoniicsclnvur,   I.tip/i^.    1S8;5;    I);i.s   C'vlindcrcpitliclcarfinoni 

dcs  .Mai:i-ns  u.  d.  Daims,  Jena,  ISSO;  llislnoo,„.sc  d.  PlatlciicpitliflUrcbsi'S.     Ik'ilr. 

V.  Ziiglcr,  xxii.,  1897;  Primaic  z.  Gcscliwnlstbild.  flilir.  EpithflerkranUuiig.  lb.. 
j       xxxii.,  iyo2. 

Heg-ar;  Zur  Aitiologie  biisart.  Geschwiilsto.     Bcilr.  z.  Gi'bli.,  iii..  1900. 
Csrael:  Aniold-ie  u.  Biolouiu  d.  Guscbwiilste.   V.  A.,  172  13ii.  190:5. 
Kahane:  Tlic.rir  d.s  C'arcinoni.     C'bl.  f.  allg.  Patli.,  vi.,   ISO"). 
/.  Karwowski:  rchcr  Cullustuniorcn.     Inaug. -Di.ss. ,  Frcihnig,  1S9.~). 
Kirmisson:  Cliinirgische  Kiaidvbcitcn  angeborciion  Ursprungs,  Stntlgart,    IS'.l',). 
Kiister:   Frageu  d.  path.  Pllan/.cnanatoniic  (Garn'nl)ildunu).     IJiol.  Cbl.,  x\.,  I'JOO. 
Liebe:  Tlicer-  iiud  ParalVuikiebs.     Schnudt's  Jalirb.,  23(5  Bd.,  l.S!)3. 
tievin:  Coll  Piolifeiatiou  under  Pathological  Conditions  witii  Especial  licfercnce  to  the 
'       Elioliigy  of  Tumors.     Studies  from  Dcpt.  of  Path.,  (Jolumhia  University.  l!)')l-03. 
Lowenthai:  Traumatische  Eutstehung  v.  Geschwiilsten.     Arch.  f.  Ulin.  Cliir.,  49  Bd., 

IS'.t.-). 
Blarchand:  Gewebswucherung  u.  Gescbwulstbildung.     D.  nied.  Wocli.,  19()3. 
Petersen  ii.  Exner:  Hefepilze  u.  Gescbwulstbildung.     Eeitr.  v.  ]5runs,  x.w.,  1899. 
Pianese:  Beitr.  z.  Histologic  u.  Actiologie  d.  Carcinoms.     J]citr.   v.  Ziegler,   Suppl., 

ISilC. 

7.  Recklingliauseii:  Adenomj-ome  u.  Cystadenome  d.  Uterus,  Berlin;  1896. 
Ribbert;  llistngeuese  d.  Carcinoms.     Vii'ch.  Arch.,  135  Bil.,  1894;  Die  Entstchung  d. 

Geschw  i'llstc.  Ueut.  med.  Wocb.,  1895;  Das  patholog.  Wachslhum  d.  Gewebe, 
I       Berlin,  189(5;  Ueber  Rlickbildung   v.  Zclleu   u.    Gewebcu   u.    die   Entsteliimg    v. 

Geschwiilsten,  Stuttgart,  1897;  Das  Gefiisssystem  der  Geschwiilsto.  D.  mod. 
I       Woch.,  1904. 

Saal:  Z.  Biologied.  Tumorea  (Parasiten),    D.  med.  Woch.,  1904, 
Schuhardt:  Entstebuug  der  Carcinome  aus  chrou.-entzundlichen  Zustilndcu,  Leipzig, 

:      1SS5. 

Schulthess:  Statistische  Untersucli.  lib.  d.  Actiologie  d.  Carcinoms.     Boitr.  v.  Ikiins, 

I       iv..  1881. 

^iegert:  Actiologie  des  Gallenblasenkrebses.     Virch.  Arch..  132  Bd.,  1893. 

Stern:  .Maligne  Tumoren  im  Kindesaltcr.     Deut.  med.  Woch.,  1892. 

Strobe:  Xenere  Arbeiten  liber  Histogenese  u.  Actiologie  des  Carcinoms.     Cbl.  f.  allg. 

i       Path.,  ii.,   1891;    Die  parasitaren  Protozoen  in  ihren  Beziehungen  zur  mcnsclil. 

Pathologic,  insbes.   zur  Histogenese  ii.   Actiologie  dcs  Carcinoms  (Rcf.).     lb.,  v., 
'       1894;  Entstehung  d.  Gliome.     Beitr.  v.  Ziegler,  xviii.,  1895. 
I^auffer:  Sarkome  auf  narl)ig  ]uii(')sem  Boden.     Virch.  Arch..  Suppl..  151  Bd..  1898. 
Volkmann:  Krobs  d.  Extroniitalcn.     Samml.  klin.  Vortr.,  Nos.  334,  335,  1890. 
Weisflog:  Ueber  Callustumoicn.     Beitr.  v.  Bruus.  x.,  1893. 
Wilms;  Die  teratoideu  Geschwiilste  d.  Hodens.     Boitr.  v.  Ziegler,  xix.,  1896. 
7.  Winiwarter:  Boitr.  z.  Statistik  d.  Carcinome,  Stuttgart,  1878. 
Wieland;  Primare  multiple  Knociionsarkome.     Inaug.-Diss.,  Basel,  1893. 
Wurz:  Traumat.  Entstehung  der  Geschwiilste.     Beitr.  v.  Brnns,  26  Bd.,  1900  (Lit.). 
Zahn:  Znr  Actiologie  dor  Epithclkrebse.     Virch.  Arch.,  117  Bd.,  18S9. 
Zenker:  Der  Krobs' d.  Gallenblase.     Deut.  Arch.  f.  klin.  Med.,  44  Bd..  18S9. 
Ziegler,  P.:   Bezioh.  v.  Trauiuen  zu  maligueu  Geschwiilsten.     Miinch.   med.  Woch., 

189.J. 

See  also  §  99. 

§  101.  When  once  a  tumor  has  arisen  in  any  ti.s.sn<'  and  lias  reached  ;i 
ertain  stage  of  development  it  may  become  quiescent  in  growth,  and 
remain  for  a  lifetime  without  uiider,i::(>iii^'  linther  clnuiiie.  iliis  is  hue 
It^artictdarly  of  those  tumors  which  according  to  their  oiigiii  :iie  ic- 
ianled  as  local  Ussue-malformatiouH ;  but  tumors  which  dexj'loj)  fii'st  in 
ater  life  may  also  come  to  a  standstill  after  attaining  a  certain  size. 
i  The  growth  of  a  tumor  takes  place  independently,  and  in  many 
?ase.s  continues  even  until  death  occurs. 

From  the  siu-rounding  tissues  the  tumor  ac(|nires  both  its  hl()(>d-\es- 
4els  and  thereby  its  food  matei-ial,  but  may  besides  grow  iiid«'pend<'nlly 
I— i.e.,  through  an  increase  of  the  cells  wliich  form  the  elements  of  the 
tumor.     In  many  cases  the  tumor  increases  in  size  es.sentially  through  an 


380 


TUMORS. 


interstitial  expansive  growth,  and  the  neigliboring-  tissue  is  onl^ 
crowded  or  piislied  aside.  In  other  cases  the  tumor  tissue  grows  b] 
infiltration  nud  forces  its  way  into  the  intercellular  S2)aces  of  the  neighhorin 
tissue,  so  that  new  areas  of  tissue  are  thus  brought  under  the  iufiueuce  o 
the  tumor.  In  this  way  the  cells  of  the  uewly  invaded  tissue  are  ofte 
excited  to  j)roliferation,  so  that  an  enlargement  of  the  tumor  takes  plac 
through  an  appositional  growth,  in  which  both  the  cells  of  the  origiugj 
tumor  and  of  the  surrounding  tissue  take  part.  I 

The  characteristic  feature  of  growth  by  infiltration  consists  in  tb 
involvement  of  the  tissues  of  the  organ  which  lie  in  the  neighborhood  of  tli, 
primary  tumor.     Further,  the  tissue  of  neighhoriiig  organs  (Fig.  242,  e,  J. 


Fig.  243.— Section  through  a 


I  iiiiaiy  <aiuer  of  the  liver  (a),  with  multiple  metastases  (h)  within  the  1  ir 
itself.    Three-sevenths  natural  size. 


may  become  involved  by  the  tumor  through  its  spread  by  contiguity,  jf 
tumor-cells  gain  eyitrance  into  the  great  body -cavities  they  may  spread  over  ]e 
serous  surfaces  and  lead  to  the  development  of  tumors.  j 

If,  in  the  process  of  infiltration,  a  tumor  gains  entrance  into  a  lymph-lr 
blood-vessel — an  event  which  in  particular  is  always  likely  to  occur  in  ie 
case  of  the  tumors  called  carcinoma  and  sarcoma — and  if  living  turn]'- 
cells  capable  of  proliferation  are  transported  through  the  lymph-  or  blo|l- 
vessels,  there  often  arise  tumor=metastases — i.e.,  a  development i'f 
daughter=tumors  which  are  not  directly  connected  with  the  prim'y 
tumor.  The  daughter-tumors  may  at  first  develop  in  the  organ  primaily 
affected  (Fig.  243,  b),  but  usually  soon  involve  other  organs  as  well  s'n 
the  case  of  rupture  into  the  lymph-vessels  the  lymph-glands  are  i'st 
affected;  in  rupture  into  the  blood-vessels,  those  organs  to  which  the  blfd 
carries  the  living  cells.  The  direction  of  the  transportation  is  usually  tjit 
of  the  lymph-  and  blood-stream,  but  retrograde  transportation  not  iute- 
quently  occurs,  particularly  in  the  lymph-vessels,  the  lumina  of  wlA 
are  easily  obstructe<l  l)y  tumors. 

The  development  of  daughter=tumors  takes  place  in  all  cases  fiim 
transported  cells.  In  the  event  of  metastasis  by  the  lymph=ves  Is 
the  aifected  lymph-vessels  (Fig.  244,  a)  are  first  filled  with  cells,  wli3h 


IXFILTKATIOX    AM)    M  KTASTASIS. 


381 


ievelop  from  tlie  transported  tuiuor-oells.  Later  there  follow  a  pro- 
iferatiou  aud  new-foriiiatiou  of  blood-vessels  on  the  part  of  the  neigh- 
boring tissue,  and  as  a  result  of  these  i)rocesses  there  de\rh»p   hiriicr  or 


Fig.  2U.— Periglandular  lymph-vessel  (in  the  axillary  region)  tilled  with  oanoer-rells  arising  from  a 
primary  carcinoma  of  the  mammary  gland  (Midler's  lliiid,  hiumatoxylin).  «,  c  aiiier-ci'lls;  l>,  wall  of 
lymph-vessel.    . .  3(X). 

smaller  nodules.  It  also  not  infrequently  happens  that  the  Ji/nijthrr.sNcIs 
are  more  uniformly  distended  hi/  the  f/roirt/t  (Fi,u".  244,  a),  without  any  real 
formation  of  nodules,  or  at  least  only  small  swelliuf;s  develop  alon.u-  the 
poui-seof  the  lymph -vessels.     luthe  event  of  metastasis  into  /;/iiij>/i-f//<nids 


m^ 


Fig.  24.J.— Metastatic  development  of  cancer  in  the  branches  of  the  portal  vein  and  llver-capillurlt-s 
'MDller's  fluid,  hiematoxvlin,  and  eosin).  o.  Liver  tissue;  Ik  plugs  of  canccr-cclIs  in  tin-  iH)rtal  vein  ;  r. 
cancer-cells  in  the  capillaries.    X  KKI. 

the  latter  become  swollen,  foiniiiiu-  ntidnhs  <A'  sinalh-r  or  lai-fi- si/,.-,  in 
which  the  tissue  of  the  lyiiipli-.uland  is  -radiially  ivplncnl  liy  lumor 
tissue. 

In  the  case  of  metastasis  throush  the  blood-vessels  t  ho  liisi  <i.\  »lop- 
meut  of  the  seeondaiv  tumor  Ix-iiis  with  tii«'  t  uiiior<-olls  loiiniii^^  Ihoom- 


382  TUMORS. 

bolus  iu  artery,  capillary,  or  vein,  and  under  certain  conditions  the  ve 
sels  (Figs.  245,  h,  c  ;  246,  b,  c)  may  be  filled  and  greatly  dilated  by  tl 
proliferating  tumor-cells.  The  tissue  in  which  the  tumor-emboli 
develops  may  at  first  remain  passive,  and  the  specific  tissue-elements- 
gland-cells  (Fig.  246,  d)  and  muscle-cells — may  vanish  as  the  result  > 
increasing  atrophy.  Later,  the  blood-vessels  and  connective  tissue  tal 
part  in  the  develojiment  of  the  secondary  tumor. 

In  the  further  course  of  its  development  the  secondary  nodule 
usually  sharply  circumscribed  from  its  surroundings  and  grows  by  e 
pansion.     It,  however,  not  infrequently  happens  that,  at  least  in  place 


Fig.  246.— Metastatic  sarcoma  of  the  liver  from  a  primary  sarcoma  of  the  parotid  (Flemming's  sohiti! 
safranin,  picric  acid),  a,  Liver-rods;  ^,  sarcoma  tissue  developing  within  the  vessels;  c,  isolated  turn  I 
cells  in  the  liver-capillaries ;  d,  liver-colls  which  have  undergone  atrophy  and  fatty  degeneration.    X  15(j 

the  infiltrative  growth  persists,  and  under  certain  conditions  widespre;! 
diffuse  tumors  develop,  particularly  in  the  bone-marrow  and  in  the  livi' 
(Fig.  246). 

The  number  of  lymphogenous  and  hieiuatogenous  metastases  vari 
greatly  in  different  cases.  At  one  time  the  metastases  may  be  confiii . 
to  one  organ,  at  other  times  they  may  be  scattered  throughout  sever; 
In  rare  cases  cells  of  the  original  tumor  may  be  spread  through  aliiK 
the  entire  body,  so  that  in  the  most  diverse  organs — glands,  muscU 
skin,  etc. — larger  and  smaller  nodules  may  aj^pear  in  quick  successio 
This  phenomenon  is  possible  when  tumor-nodules  situated  in  the  luii 
pleura,  or  bronchial  glands  break  into  a  pulmonary  vein,  or  when  t 
tumor  cells  pass  through  the  lungs. 

If  a  living  bit  of  tumor  (carcinoma,  sarcoma)  capable  of  formii 
metastases  is  transplanted  from  one  animal  into  the  tissues  of  anothr 
animal  of  the  same  species,  it  sometimes  happens  that  it  will  develop 
the  second  animal.  There  may  take  place,  therefore,  a  metastasis  fr( 
one  animal  to  another.  In  man,  tumor  particles  may  in  a  similar  manii 
be  transplanted  during  operations  from  one  part  of  the  body  to  anotht 
and  there  contine  to  grow  (implantation  metastasis). 

Side  by  side  with'the  i>i()gr«'ssive  proliferation  of   tissue  there  ve 
frequently  occur    in    tumors    retrogressive    changes,    particularly 
rapidly  growing  and  infiltrating  cellular    tumors,   in  which  fatty   a| 
mucous  degeneration,  necrobiotic  processes,  and  htemorrhages  may  ta  \ 


I 


EXTIRPATION    AND    RECrHHENTE    OF    TIMOHS. 


ns;j 


j)lac'e  to  a  markt'd  (leccree,  so  that  tluMc  not  iiirr('(nu'ii(ly  results  a  total 
^(•.struct ion  of  ihr  tumor  fi.s.sur.s.  This  rapid  disiiit('<;iat  ion  of  llic  lunior  is 
ill  part  due  to  the  fact  that  in  eaiciiioinata  the  epithelial  proliferation  to 
|i  very  jii-eat  extent  throws  into  the  bltxxl-vesscls  and  so  ohst  rncts  lliciii. 
if  the  eells  are  badly  nourished  they  may  uiider<j;o  nrcrosis  and  liecoiiie 
lissolved  thiou<;h  the  action  of  proteolytie  ferments.  Jn  the  ease  of 
iodular  tumors  the  destruction  of  the  tumor-cells,  when  follo\v«'d  by  .1 
•esorption  of  the  i)roducts  of  de.t2;eneration,  h-ads  to  ,s7/ /•/«/.///// and  to  the 
"ormation  of  cU-atrh'ial  contractions.  Very  often  ilcifcncrntion-ciist.s  and 
(leers  may  be  thus  formed;  and  ])arti('ularly  in  the  <'ase  of  carcinomatous 
uuiors  of  the  mucous  membranes  the  parts  of  the  tumor  <,Mo\viii.ii-  up 
ibove  the  surface  very  often  for  the  greater  part  underjio  disiiilei;ration. 
u  slowly  cjnwin.i;  tumors  of  hard  consistency  extensive  retroji^rade 
changes  do  not  usually  occur. 

i  The  necrosis  and  tlisiiitegration  of  the  tissues  of  the  tumor  only  very 
jarely  terminate  in  a  cure.  This  event  is  most  likely  to  happen  when  \x 
)olypoid  new-growth  becomes  totally  necrotic  (for  example,  as  a  result 
.f  twisting  or  tearing  of  its  pedicle)  and  is  thrown  off.  In  the  majority 
jif  the  tumors  showing  a  tendency  to  retrogressive  changes  and  disinte- 
|;ration,  while  the  older  portions  are  dying  the  growth  <-onstantly  ad- 
I  vances  at  the  i)eriphery,  so  that  new 

tissues    aie    being    i)rogressively   at- 
tacked by  the  tumor. 

If  the  tumor  is  extirpated,  there 
may  result  a  cure  when  all  of  the 
growth  has  been  removed  or  de- 
stroyed. This  is  most  easily  accom- 
plisiied  in  the  case  of  slowly  growing 
and  sharply  circnmsciibed  tumors 
M'hich  increase  by  expansion.  \n  the 
case  of  intiltrating  tumors  it  is  very 
difficult  to  determine  the  l)onndary 
of  the  tumor-growth,  since  this  may 
often  extend  far  beyond  the  point 
where  any  macrosco])ic  change  in  the 
tissue  is  apjxirent.  C'onse<pient  ly,  in 
such  cases  there  takes  ])lace,  sooner 
or  later,  in  the  operation  scar  a  re- 
currence (Fig.  247,  a)  which  aris<'S 
from  i)ortions  of  the  tunntr  remaining 
in  the  tissues.  Such  recni-r<Mices  be- 
have exactly  like  the  primary  tumor, 
and  may  also  form  metastases  (Fig. 
247,  c).  In  those  cases  in  which  re- 
currence in  the  scar  foll(»wiiig  op- 
eration is  lung  delayed,  it  is  jxissible 
that  this  circumstance  depends  upon 
the  fact  that  in  the  afTected  aiva  the 
conditions  furoriii;/  tnmur  ilrrrlopnirnt 
a  (/((in  occur. 

According    to    their    clinical    and 

anatomical     characterisf  ics     tumors 

lay  be  classed  as  benign  and  r-nalignant.     As  hcnif/n  tumors  are  geiH-r- 

dy  regarded  those    (cliic/i  (/roir  slmrli/  oiid  Ix/  c.vjxdisioii   ((ml  do  xot  forni 

)eta8t((S('S ;  as  oudignuid,  those  ichich  shoic  a  complete  cmdiicijiolion  from  the 


fi(,.  U<.  Ki-curtfiit  sarcDiiia  in  the  ainpiita- 
<>n-stunip  (if  111..  fiMimr.  a.  Fungoid  lunior 
rising  from  tin'  bone-marrow;  h,  periosteal 
'Kluies;  c,  meta.stasis.    One-tialf  natural  size. 


384  TUMORS.  I 

I 
normal  Jaws  of  proliferation^  groic  quicldy  and  hy  infiltration,  easily  undeio 
degenerative  changes  and  form  metastases.  . 

The  malignant  tumors,  on  the  whole,  coincide  with  those  tniir 
forms  which  are  known  as  carcinoma  and  sarcoma.  It  must,  howe\r, 
be  borne  in  mind  that  the  malignancy  of  a  tumor  depends  not  only  u]  u 
its  character,  but  also  upon  its  location.  A  benign  tumor  takes  o  a 
malignant  character  as  soon  as  its  presence  interferes  with  the  fuuctiiis 
of  vital  organs.  Hence  eveiy  tumor  of  the  brain  or  meninges  becom*  a 
dangerous  affection  at  the  moment  when  it  gives  rise  to  disturbance;  )f 
the  cerebral  functions.  Under  certain  conditions  such  benign  tumor,is 
fibromata  of  the  uterus  become  destructive  growths  as  soon  as  they  rch 
such  a  size  as  to  displace  and  compress  the  neighboring  organs. 

After  a  tumor  has  existed  for  a  certain  period  there  results  v;y 
frequently  a  marked  lowering  of  the  general  nutrition,  a  marasu  s, 
which  is  usually  designated  tumor=cachexia.  This  occurs  chiefly  in 
association  with  the  malignant  growths  known  as  cancer  and  sarcoia; 
and  may  depend,  in  part  at  least,  upon  the  great  demands  made  uponle 
food  supply  by  the  rapid  growth  of  the  tumor,  particularly  in  the  <jse 
of  formation  of  metastases.  A  still  more  important  cause  may  lie  iuae 
fact  that  the  tumor  may  interfere  with  the  taking- in  of  food.  In  cailer 
of  the  oesox)hagus,  stomach,  and  intestine  the  fimction  of  the  affe-^ 
organ  is  greatly  interfered  with,  and  the  assimilation  of  food  nia^jbe 
entirely  prevented  or  nearly  so.  Further,  it  should  be  borne  in  n|id 
that  through  the  degeneration  of  the  tumor  and  the  continuous  secre-Jii 
from  the  resulting  ulcers  large  amounts  of  albuminous  material  jay 
often  be  lost  from  the  body;  and  that  through  putrid  decomposioii 
there  may  arise  substances  which,  when  absorbed,  may  act  injurioly 
upon  tlie  organism.  Finally,  the  pain  which  is  often  felt  in  a  tu^or 
may  rob  the  patient  of  his  sleep.  Whether  the  tumor  itself,  in  cer'iii 
cases,  produces  substances  harmful  to  the  organism  is  yet  unknown,  j'Ut 
is,  however,  not  improbable. 

Metastases  occasionally  occur  with  benign  tumors,  chondromata,  myoi  ta, 
and  adenomata.  Of  these,  the  metastases  in  the  bones  of  thyroid  tumors  are  of  s{  ;ial 
importance;  they  occur  when  no  carcinomatous  prohferation  can  be  demonstrat;  in 
the  thyroid,  so  that  it  would  seem  probable  that  under  certain  conditions  eve:the 
cells  of  a  normal  or  hypertrophic  tissue  may  be  transported  into  the  bone-ma^^o^^nd 
there  proliferate.  i 

Literature.  a 

(  Tumor-Metastasis. )  ! 

Acker:  Zur  Pathogen,  d.  Geschwulstmetastase.  Deut.  Arch.  f.  kl.  Med.,  xi.,  ^73. 
Andre :  Entsteh.  d.  Geschwiilstmetastasen  auf  embol.  Wege.  Virch.  Arch.,  61  Bd., i94, 
Arnold:  Ueber  rticklaufigen  Transport.     Virch.  Arch.,  124  Bd..  1891.  \  ; 

Audibert:   De  la  generalisat.  du  cancer  de  I'estomac,  Paris,  1877.  i  , 

Beneke:  Freics  Wachsthum  metast.  Geschwulstelemente  in  serosen   Hohlen.     ^t. 

Arch.  f.  kJin.  Med.,  64  Bd.,  1899.  ij 

Borrmann:  Metast.  bei  gutart.  Tumoren.    Verb.  d.  D.  path.  Ges.,  vi..  Jena,  igO-JI 
Geissler:   Uehertragbarkeit  d.  Carcinoms.     Langenbeck's  Arch.,  46  Bd.,  1893.   1^_ 
Goldmann:   Verbreitimgswege  bosartiger  Geschwtilste.     Beitr.  v.  Bruns,  xyiii.,  mi- 
Hanau:    Erfolgreiche  exp.  Uebertrag.  v.  Carcinom.     Fortschr.  d.  Med.,  vii.,  ISM 
Hedinger:    Intiina  .Sarkomatose  d.  Art.  u.  Yenen.     V.  A.,  164  Bd.,  1901.  ;  ' 

V.  Kahlden:  Carcinomrezidive.     A.  f.  klin.  Chir.,  68  Bd.,  1902. 
KantOiOwicz:  Pathogenese  der  allgemeinen  Carcinomatose.     Cbl.   f.  a.  P.,  iv.  p93. 
Lanz:   Uebcrtragbarkeit  melanot.  Geschwiilste.    Festschr.  f.  Kocher.  Wiesbaden  .®1. 
L,oeb:  Transplantation  von  Sarkom.     V.  A.,  167  Bd.,  1902,  u.  172  Bd.,  1903.  . 

Morau:  Rech.  exp.  surla  transmissib.de  cert,  neoplasmes.  Arch,  de  med.  exp..'^-*- 
Perls:  Beitr.  z.  Geschwulstlehre.     Virch.  Arch.,  56  Bd.,  1872.  • 

Patrick:  Vcrbreit.  d.  Carcinoms  i.  d.  Lymphdriisen.  Deut.  Zeits.  f.  Chir.,  32  Bd.'|91. 
Schmidt:   Die  Verbreitungswege  der  Carcinome,  Jena,  1903. 


FIMHOMA. 


liSf) 


lliMKlos.     Z.  f.  Krohsforschiinir.  i..   l!t(ll 
t'r(>  Ration.     Wicti.  inctl.  Jil..  IVis. 


ISC, 


sticker:  Transplnntahle  Lyniphos:irkoiiu> 
Velich.:  Ueliertrajr.  v.  Rattensarkoin  aiif 
Virchow:  Dio  krankh.  Cioschwiilsto,  i.-iii. 
Weber:   Zur  Ciosch.  dcs  Knchomlroins,  naiiuMitl.  in  Hoziisr  nuf  doss,  licrod.  Vi 

u.    seciind.    Vcrhreit.  in  inn.  Orfianon    d.    i:inlit)lic.      \irch.   Arcliiv,  A't  H<l. 
Wilmanns:    Iniplantationsro/.idive.     licit r.  v.  Hrnns,  42  Hd.,  I'JOl. 
Winkler:   Betheil.  d.  Lynipliccfassean  d.  Mi-tast.    Virch.  Arch.,  1.">1  Hd. .  Sii|.p|.,  1S<)S. 
Zahn:    loher  rioscliwulstnicla.'itason.     Vircli.  Arcli.,  117  Bd.,  ISS'.t. 
Zenker,  K.:  ZiirLcinc  v.d.  Metastascnl>iUl.  d.  Sarkoinc.     Vircli.  Arch.,  120  H<i..  I.SOO. 

8ce  also  §  125. 


)rk()ni. 

,  i.sc.t;. 


The  Different  Forms  of  Tumors. 


I.  TrMo us  Dkrivkd  v 


D.^I    COXXHCTIVI;    Tlf 

Framfavokk. 
(d)  Fibroma. 


>u-  Tin;  .srpi' 


§  lOi'.   .\.  fibroma  i: 
occurs  jnost  frequently 


luiuor  com 
tli<'  lonu  () 


Pig.  -48.— Hard  fibroma  from  lobe  of  the  ear  (alco- 
hol, hoematoxylin).  n.  Lonsritudinal  se<'tion ;  o,  trans- 
verse siTtion  iif  bundles  <>f  Ubres.     X  40U. 


i)S('(l  {){  Jihnnis  rniinrrtirr  H.s.sik  .  \{ 
iKxhdr.s,  which  iirc  sharply  circmii- 
scrihcd  fioiu  Ihc  siiiiomidiii;;  tis- 
sues, aud  usually  involve  but  a  ]wr- 
tiou  ot"  the  all'ecteil  orjiaii.  Yei\v 
rarely  aiu'iit  ire  organ  (ovary  )  may 
become  chaiiixed  into  a  sin;;ie 
Itimor-iiiass.  On  a  free  epitlic- 
lial  siiitace  and  on  mncoiis  mem- 
branes ;i  lildoma  may  appear  in 
the  form  of  wpitplUouid  or  a  pithijt. 
Aceordinjj:  to  the  character  (tf 
the  connective  ti.ssue  of  which  it 
is  coinpo.sed,  the  consi.stency  (d"  a 
libroina  may  ^■ary  j^really.  ()fl«Mi 
it  is  lund  and  hnif/li,  creaking  un- 
der the  knil'e('/'w//'>/'/),  and  sliow- 
ing  on  its  cut  surface  a  white,  tendon-like,  sliiiiini;  tissue;  but  in  oilier 
c;tses  the  growth  may  be  soft,  flaccid,  the  cut  surface  being  more  uni- 
formly grayish  -  white 
and  somewhat  tran.slii- 
cent.  In  still  other  cases 
the  individual  strands 
of  connective  tissue  are 
indeed  wiiite  and  shin- 
ing, ])ut  the  tumor  as  a 
whole  has  a  looser  struc- 
ture and  is  correspond- 
ingly Ha<('id. 

IJelweeii      the      hard 
and  soft  growths   there 
exist  all  ])o.ssil)le  transi- 
tion-forms, and  even  in 
I  one    tumor     different 
[  parts  may   possess  dif- 
ferent characteristics. 
Under    the    microscope 
I  the  hard  kinds  appear  to  be  compos<'(l  chiefly  of  thick  bundles  of  cnars*' 
I  fibres  (Fig.  L>4S,  a,  h),  in  which  lie  scattered  a  larger  or  smaller  number 
of  cells.     In  the  softer  forms  the  bundles  .d"  fil)res  are  mure  delicate 


Fio.  349.— Swtlon  of  an  (i-dt-Miatoiw  llbniiria  of  tlif  iiUTiin  (iwnilc 
acid,  Klywrln).  (i.  Closi-lv  lv(n(f  tlbn-s;  /),  llbri-s  |tn>».s«Ml  H|>nrt  by 
lliiid:  r,  splndlf-sliaiwd  r.-ll.s ;  </,  .swiillfri  nmnd  n-ll.s;  r,  blood- 
v.'ss.-l.    .-.  :'.(»). 


386 


TUMORS. 


(Fig.  249,  a).  If  as  a  result  of  venous  congestion  or  other  cause  a  clear 
fluid  collects  between  the  fibrillje,  there  is  formed,  an  (edematous  fibroma, 
whose  bundles  of  fibres  (Fig.  249,  h)  are  pressed  apart  by  the  fluid,  the 
tissue  becoming  softer  and  more  moist  and  translucent,  and  finally 
resembling  the  tissue  of  the  umbilical  cord. 

The  soft  forms  of  fibroma,  which  present  a  partly  translucent,  grayish- 
white  cut  surface,  are  usually  very  rich  in  cells ;  so  that  it  is  possible 
by  teasing  to  isolate  numerous  slender  spindle-shaped  cells  (nuclei  with 


Fig.  250.— Fibroma  pencaiialiculare  inaninue  (Miiller's  fluid,  alum  carmine,  eosin).    a,  Gland-tuhules ;  b, 
newly  formed  pericanalicular  connective  tissue  rich  in  cells ;  c,  connective  tissue  poor  in  cells.    X  35. 


tails).  The  intercellular  substance  is  correspondingly  less  in  amount, 
the  fibrillfe  more  delicate  and  arranged  in  finer  bundles.  Sections 
through  such  fibromata,  when  stained,  appear  very  rich  in  nuclei  (Fig. 
250,  h). 

Fibromata  develop  from  proliferating  connective-tissue  cells,  and  it 
is  usually  i)0ssible  to  find  in  the  tumor  certain  areas  which  are  richer  in 
cells  than  the  main  mass  of  the  tumor  tissue,  and  in  which  the  cells  j 
appear  not  only  as  small  spindle  cells,  but  also  in  part  as  round  cells,  or 
as  short,  thick  spindles,  or  even  as  stellate  cells.     The  transformation  of ! 
the  newly  formed  cellular  tissue  into  connective  tissue  takes  place  in  the  i| 
same  way  as  that  described  under  Hyperplasia  of  Connective  Tissue.     A  i 
new-formation  of  elastic  fibres  is  usually  wanting,  but  at  times  such  a  j 
new-formation  does  occur,  particularly  in  the  neighborhood  of  the  blood- ^j 
vessels.  \ 

Fibromata  may  appear  in  any  part  of  the  body  which  contains  any^ 
form  whatsoever  of  connective  tissue.  They  occur  most  frequently,  forj 
example,  in  the  nerves,  skin,  periosteum,  fascia,  mammse,  and  mucousj 
membrane  of  the  nose ;  more  rarely  in  the  ovary,  intestinal  tract,  etc.ij  ^ 
In  the  mammary  gland  the  development  of  the  fibroma  takes  place  par- 
ticularly around  the  canaliculi  (Fig.  250,  b),  so  that  the  latter  come  to| 
be  surrounded  by  connective  tissue  rich  in  cells.  : 

Fibromata  do  not  form  metastases,  but  often  occur  as  multiple  tumors,n 
especially  in  the  nerves  and  skin  (see  IS'eurofibroma,  §  111).     Moreover,]'] 


MYXOMA.  387 

is  not  uncommon  to  see  within  a  tumor  several  centres  of  j;ro\vtli — lliat 
.  tlu  niassof  the  tumor  is  made  up  of  several  nodules  or  bands  ludd 
-cilier  by  ordinary  connective  tissue  (Fig".  250,  b).  Fibromata  are 
alii:iiant  only  throu<j;h  their  size  and  i)osition. 

Fibi'omata  may  nnd(>rgo  mucous  or  fatty  dejieneration  or  may  soften 
ad  disintejirate,  so  that  cavities  may  be  formed  witldn  them.  They 
ay  also  break  thiouuh  and  oive  rise  to  ulcers.  Their  blood-su]>i)ly 
'iries  <;ivatly,  at  times  beini::  scanty,  at  otiiei-  times  abundant.  Occasion- 
jly  the  blood-vessels  are  ectatic,  so  that  th«>  tissue  is  intersj)ersed  with 
■"ide  channels  and  clefts,  from  which  blood  esca])es  Avlien  the  tumor  is 
camiued  in  a  fresh  state.  In  other  cases  dilated  lymi)h-channels  are 
ten. 

Keloid  is  the  designation  applied  to  a  hard,  nodular,  oi-  tlat  and 
Inded,  or  stellate  growth  of  the  skin,  which  in  its  fully  develojKnl  state 
(usists  of  dense  fibrous  tissue  without  elastic  fibres.  The  direction  of 
te  fibres  is  often  at  right  angles  to  the  surface  of  the  skin,  or  at  least 
oes  not  accord  with  that  of  the  normal  lil)res.  It  usually  develoi)s  after 
ijuriesor  intlammations  {cicatrix-keloid),  but  it  may  also  appear  without 
^(•li  association  {spontaneous  keloid).  The  cause  of  the  keloid  growth  is 
)t  known;  the  tendency  to  recurrence  after  removal,  the  multiple  oc- 
(rrence,  and  the  fact  that  many  cases  frequently  occur  in  the  same 
finily  ( Hutchinson)  speak  in  favor  of  a  special  predisposition  on  the 
1  rt  of  the  skin. 

Literature. 

{Fibroma  and  Keloid.) 

ichoff:  Gescbwiilste.     Ergebn.  d.  allg.  Path.,  v.,  1900. 

Jcobson:  Keloid.     Arch.  f.  klin.  Chir.,  xxx.,  1884. 

Jres:   Elastiscbe    Faseru    in   Bindegewebsgeschwiilsten.     Beitr.    v.   Zieeler,   xxvii., 

1900,  p.  389. 
Jseph:  Ueber  Keloide.     Arch.  f.  Derm.,  49  Bd.,  1899. 
Jrgens:  Priniare  ilerzgesclnviilste.     Berl.  klin.  Woch.,  1891. 
Inghans:  Keloid.     Virch.  Arch.,  40  Bd.,  1867. 
Ison:  Sur  la  eheloide  inguinale  spontanee,  Paris,  1887. 
Iterson:  Ovarian  Fibromata.     American  Gynaecology,  1902  (Lit.). 
V Recklinghausen :  Ueber  die  midtiplen  Fibrome  der  Haut.  Berlin,  1882. 
Eiiitz:  Wahres  Keloid  combin.  mit  Narbenkeloid.     Arch.  f.  Derm.,  29  Bd.,  1894. 
lorn:  Spontanes  Keloid.     Arch.  f.  klin.  Chir.,  51  Bd.,  1895. 
tna:  Die  Histopathologic  d.  Hautkrankheiten,  Berlin,  1894. 
■Vi-ims:  Patliogenese  des  Keloids.     Beitr.  v.  Bruns,  23  Bd.,  1899. 

See  also  §  112. 

(b)  Mijxoma. 

i  10.3.  A  myxoma  is  a  tumor  which  consists  essentially  of  mucous 
tiiue,  and  is  made  up  of  cells  and  a  fluid  or  gelatinous  intercellular  sub- 
Sjnce  containing  mucin.  The  cells  of  the  tumor  ai-e  for  the  greater  ])art 
p(iymori)hous,  with  processes  of  varying  length  (Fig.  2.")1)  which  anas- 
t^iiose  with  one  another  (Fig.  2.52,  a).  The  tissue  is  markedly  ti-ans- 
hjent,  soft,  and  the  blood-vessels  are  easily  seen  through  it.  l'i(»m  the 
c*  surface  gelatinous  masses  or  a  stringy  fluid,  which  swell  u])  in  watei-, 
njy  be  obtained. 

I  No  tumor  is  ever  wholly  made  up  of  myxomatous  tissue;  the  latter 
i^isually  combined  with  otiier  forms  of  tissue,  particularly  Mith  fibrous 
C'mective  tissue,  fat  tissue,  cartilage,  and  sarcomatous  tissue.  I-'or  this 
rt'son  such  tnmors  are  properly  designated  fibromyxoma,  lipomyxoma 
(-g.  254),  chondromyxoma  (Fig.  257.  e),  and  myxosarcoma  (Fig.  i*52). 


388 


TUMORS. 


Mucous  tissue  may  develop  from  fibrous  couneetive  tissue  througi 
the  collection  of  a  muciu-coutaiuiug  fluid  between  the  tibrillre  and  tii( 
gradual  disappearance  of  the 
latter.  Adipose  tissue  may 
pass  over  into  myxomatous  tis- 
sue through  the  disappearance 
of  fat  from  the  fat-cells  and  the 
appearance  of  a  mucin -contain- 
ing gelatinous  substance  be- 
tween the  cells,  during  which 
process  the  fat-drops  become 
broken  up  into  swollen  droplets 
(Fig.  254,  h,  c),  while  the  cells 
themselves  become  smaller  and 
star-shaj)ed  (d).  Cartilage  may 
also  become  transformed  into 
mucous  tissue  tlirough  a  mucoid 
degeneration  of  the  basement - 
substance  and  a  change  of  form 
of  the  cells  (Fig.  257,  c,  d). 
Myxosarcomata  (Fig.  252)  arise 
either  through  a  local  increased 
activity  of  cell-proliferation  in 
myxomata  or  through  a  collec- 
tion of  mucoid  substance  be- 
tween the  sarcoma  cells. 

Myxomata,  myxofibromata,  and  myxolipomata  develop  most  f 
queutly  iu  the  connective  tissue  of  the  periosteum,  skin,  heart,  fasc 
and  sheaths  of  the  muscles,  as  well  as  in  the  fat  tissue  of  the  subcu 


Fig.  251.— Cells  from  a  myxoma  of  the  periosteiii' 
the  femur  (gold  preparation).    >.  iW. 


.W 


w^ 


'^^ 


r 


Fig.  2.")2.— Seption  of  a  myxosarcoma  (Miiller's  fluid,  carmine,  {rlycerin).    a.  Myxomatous  tissue}  b,s 
of  cells;  c,  fibrous  tissue.     X  225. 


neous  and  subserous  tissues  and  of  the  endosteum.  Myxochondrcata 
occur  particularly  in  the  parotid,  and  constitute  the  most  common  rm 
of  tumor  found  there. 


I 


LIPOMA. 


389 


These  forms  are  all  benijjn  tnmois,  which  rarely  ])ro(liK'('  nietastjises, 
lyxosaieoniata,  on  the  other  hand,  have  the  characleristics  of  sjireomata 
^id  may  foi-m  metastases. 

Literature. 

(Mi/.roma.) 

ijrthenson:  Myxomo  dc  rnroillettc  gauche.     Anli.  do  mod.  cxp.,  IHO.*?. 

}?rtz:  Myxom  iin  rcclitcn  Seitcuvcntrikel.     Vircli.  Arch.,  49  B(i.,  1H70. 

l-yfelder:  Zur  Kcsection  dcs  Oberkiefers.     Virch.  Arch.,  11  Bd.,  18.")7. 

Jrgens:  Primilre  Ilcr/.iicschwulsto.     Berl.  klin.  AVocli.,  18'.)l. 

lister:  Myxom  u.  odemat.  Bindcgewebe.     Sitzber.  d.  Kicdcrrhcin,  Gcs.   f.  Xalnrk  , 

issi. 
liller,  J.:  Myxom.     Arch.  f.  Anat.  u,  Phys.,  1836. 

(th:  Schlcim  II.  Schlcimgeschwulste.     Ges.  d.  Wissensch.  zu  (Jottiiiircu,  1S!).1. 
Iibin:  Myxome  du  canir.     Arch,  dc  med.  exp.,  1893. 
Iimler:  Ucber  ^Myxom.     Inaug.-Diss.,  Bonn,  1881. 
■\rchow:  Myxoin.     Virch.  Arch.,  11  Bd. ;  Geschwiilsfc,  i.,  18G:3. 
Signer:  Collonema  im  Gehirn.     Virch.  Arch.,  8  Bd.,  1855. 
\3icl1selbaum :   ;Mvx()m  d.  Oberscheukels  m.  secund.  Knoten  in  d.  Lunge.     Virch. 

Archiv,  5-1  Bd.,  1873. 

(c)  Lipoma. 

§104.  A  lipoma  is  a  tumor  consisting  of  adipose  tissue  (Fiji;.  2.5.3 ). 
lese  tumors  are  sometimes  soft,  almost  tluetuatinj;-,  sometimes  firm, 
iliiallj' nodular  and  lobulated,  and  very  often  attain  a  very  <ireat  si/e. 
Ij  structure  they  are  very  similar  to  the  subcutaneous  adipose  tissne — 
tit  i.s,  they  consist  of  fat-lobules  held  together  by  thick  or  narrow 
ciuiective -tissue  trabeculse. 

Histologically,  the  tissue  of  a  lipoma  resembles  the  fa( -lobules  of 
t;  subcutaneous  panniculus  (Fig.  25;>),  although  the  tendency  to  form 
t  )ical  grape-like  clusters  of  fat-cells  is  wanting.     If,  as  not  inf i-equent  ly 

happens,  mucous  tissue  is  also 
formed  in  connection  with  tlie 
fat  tissue,  or  if  the  latter,  fol- 
lowing a  disappeai-ance  of  its 
fat,  becomes  changed  into  myxo- 
matous tissue,  the  tumor  is  des- 
ignated a  lipomyxoma  TFig. 
2.54);  if  there  is  an  abundance 
of  libi-ous  tissue  ])iesen1,  it  is 
called  a  lipofibroma  or  fibroli- 
poma. 

Jjipomata  develop  most  com- 
monly  from   adi])ose   tissue,    but 
may  arise  also   from    connective 
tissue  which  normally  contains  no 
fat.     Calcihcatiou,   neci-osis,  gan- 
grene,  and  sloughing  are  of  not 
infie(pient  occunencc;  in  lij)omala 
of   large  si/e.     These  tumors  do 
ik'  produce  metastases,  but  are  occa.sionally  of  multiide  occurrence.     A 
nplete  disappearance  of  a  lipoma  does  not  take  i)lace  in  the  case  of 
reme  general  emaciation  of  the  individual. 
Lipomata  are  sometimes  observed  even  in  new-born  children— for 


? 


f^^ 


sr.  2.53.— Lipoma  of  shoulder  reEion,  with  relativclj 
»\ll  tat-teils  (Muller's  HuiU,  haematoxyiin).     X  300. 


390 


TUMORS. 


example,  as  tumors  developing  in  or  over  the  cleft-formations  of  sp  a 
bifida — but  tliey  occur  much  more  frequeutlj^  iu  later  years.  The  vjit 
common  seats  of  these  growths  are  the  subcutaneous  tissues  of  the  ba :, 


Fig.  254.— Lipomyxoma  of  the  back  (Miiller's  fluid.  Van  Gieson's).    o.  Large  fat-cells;  b,  C,  fat-oil  tD 
which  the  fat  is  broken  up  into  little  droplets ;  d,  mucous  tissue ;  e,  blood-vessel.    X  300.     ' 

buttocks,  neck,  axilla,  abdomen,  and  thigh ;  but  they  are  found  al;  in 
the  intermuscular  connective  tissue,  subserous  fat  tissue,  in  the  kidi.fs, 
intestine,  mammary  gland,  under  the  aponeurosis  of  the  forehea  in 
the  meninges,  skin,  fingers,  lymph-glands,  joints,  etc.  They  may  cur 
as  multiple  growths,  and  in  such  cases  maybe  symmetrically  distribiid. 
In  man  there  may  occur  a  formation  of  fat  tissue  about  the  neck  .nd 
throat,  leading  to  nodular  and  lobulated  disfigurations  of  the  skin  ol  his 
region,  and  giving  occasion  for  the  designation /«%  collar  (Madelig). 
The  development  of  fat  in  these  cases  takes  place  partly  in  the  sub*.ta- 
neous  tissue,  partly  iu  and  under  the  fascia  and  between  the  mus'tes. 
An  abnormal  development  of  fat  in  an  extremity  may  give  rise  o  a 
condition  of  lipomatous  elejyJiantiasis.  Should  the  process  extend  t:the 
trunk  and  upper  extremities,  etc.,  conditions  are  established  whic. re- 
semble very  closely  general  obesity. 


Literature. 

{Lipoma.) 


Adami:  Retroperitoneal  Lipoma.     Mont.  ]\[ed.  Jour.,  1897, 
Alveoli :  La  genesi  del  lipoma.     Policiiuico,  1900. 
Askanazy:   Entsteh.  multipler  Lipome  in  Lvmphdrlisen 

1S<)<». 

Blaschko:  Erbliche  Lipombildung.     Yircli.  Arch.,  124  Bd.,  1891. 
Brohl:  Zur  Aetiologie  u.  Statistik^dcr  Lipome,  Wiirzhurg,  1886. 
Ehrmann:   Multiple  sj-mmetrische  Xantlielasmen  u.  Lipome.     Beitr, 

1888. 
Goebel:  Ueber  multiple  Lipome.     Cbl.  f.  allg.  Path.,  vi.,  1895  (Lit.— Uebers>. 
Grosch:  Studien  liber  das  Lipom.     Dtsch.  Zeitschr.  f.  Chir.,  xxvi.,  1887. 
Koettnitz:  Svmmetr.  Auftreten  der  Lipome.     Zeitschr.  f.  Chir.,  38  Bd.,  1894. 
Langer:  Multiple  evmmetrische  Lipome.     Arch.  f.  klin,  Chir.,  46  Bd.,  1893. 


Yirch.  Archiv,  15, Bd., 


Bru)Jv.| 


N 


CIIOXDKOMA. 

Iffadelimg:  Ucbcr  den  Fctthals.     Langi'iihfck's  Arch.,  xxxvii,,  1888. 

Mestre:   Kssai  sur  Ic  lipoiiR',  .Montpi'llicr.  ISU'J. 

Miiller:   Lipoine  d.  ^■il■^c■u.     Viirh.  Airli.,  14;")  IJd..  iSDi;. 

Steinheil:   Ichcr  Liponu' dor  Hand  u.  Fiiiiri-r.     licitr.  v.  Uniiis,  vii.,  18JU. 

Virchow:  Die  Krjiiikhiiften  GcsclnvlUsto,  i.,  ISfi:}. 

Warthin:  Fihrolipouia  of  tlic  Kidney.     JcMir.  of  Patli.  and  IJact.,  IS't?. 


301 


(d)    ('/i(Hi(lr<>»ui. 

§105.  A   chondroma  or  enchondroma  is  a  liiiiior  consist  ii 
tijilly  of  caiiiUu/i'.     The  aniount  of  coimoctiM'  1  issue  taking;  ]>a 
structure  of  the  tumor,  in  part 
covering;:  its   surface  or  acconi- 
panyiug  the   blood-vessels  into  ,    •  \   .  '    '  •  *   "* 


^  e.s.seii- 
1    in  tlir 


Fio.  25-5.— Periosteal  chondroma  of 
pbalanx.    Natural  size. 

Fig.  256.— Section  from  a  chondroma  of  the  ribs  (ha»matoxylin, 
cells;  b,  canilat'e  rich  in  large  cells.    X  80. 


0     ^       - 


Fig.  ZVt. 
.digital  phalanx,  seen  in  longitudinal  section,    a.  Chondroma;  h. 


■arinlne).    «,  Ciirtlhign  rfrh  In  siniill 


its  interior,  is  so  slight  as  to  fall  completely  into  thc^  l)a('kgi-ouml  wlini 
compared  with  the  cartilage. 

Chondromata  develo^j  chiefly  in  tho.se  ])laces  where  caililage  is 
found  normally — that  is,  iu  the  osseous  system  or  in  the  cartilages  of 
the  respiratory  tract;  but  they  also  occur  in  tissues  whicli  normally 
pos.sess  no  cartilage — for  example,  iu  the  salivary  glands,  ])articulaily  in 
the  i)arotid,  and  in  the  testicles,  and  more  raicly  in  other  organs.  In 
the  bones  they  develop  from  remains  of  cartilage  which  jicrsist  after  ossi 
fication,  in  the  case  of  bones  developing  from  cartilage;  but  more  often 
jtake  their  origin  from  the  periosteum  and  endosteiini  (Fig.  '.'^r*).  They 
form  tumors  which  vary  greatly  in  size.  The  small  ones  :ire  nsn 
ally  spherical  (Fig.  255);  the  larger  ones  nodulai-  oi-  lobulatcd.  'I'Im- 
individual  nodules  are  often  .separated  from  one  another  by  connective  tis- 
sue. Xot  infre(iuently  they  are  ninltii)le,  ]iait icularly  in  the  skeleton, 
ind  here  again  of  most  fie<iuent  occurrence  in  the  hands  and  feet  and 
also  in  the  testicles. 

The  tissue  of  an  enchondroma  presents  most  often  the  charact<Tistics 
of  hyaline  cartilage  (Fig.  25(5),  moie  rarely  that  of  n'ticular  or  fibrous 
cartilage.  At  the  periphery  of  the  tumor  the  cartilage;  i):is.ses  over  into 
connective  tissue,  which  forms  a  kind  of  iiei-ichondrium. 

The  number,  size,  form,  and  grouping  of  the  cartilage  cells  \ary 
greatly  in  different  cases  and  also  in  dilVerent  iKirts  of  the  same  tumor. 
Many  enchondromata  art;  Aery  cellular  (I-'ig.  2.")tl).  others  poor  in  cells, 
many  contain  large  cells,  otheis  small  cells,  or  both  large  and  small  <'ells. 


392 


TUMORS. 


%. 


.<-</• 


The  cells  are  sometimes  surrounded  by  the  so-called  capsule,  at  other 
times  not;  sometimes  they  lie  in  groups  inside  of  the  mother-cajjsule  at 
other  times  they  are  more  ' 

regularly  distributed.     All  _  

the  varieties  of  cartilage 
occurring  normally  in  the 
organism  are  found  in  en- 
chondromata.  Accord- 
iugly  the  cells  A'ary  in 
form,  the  majoritj^  show- 
ing the  familiar  spherical 
form,  but  spindle  and  stel- 
late cells  are  not  rare, 
particularly  in  the  neigh- 
borhood of  the  connective- 
tissue  bands  which  divide 
the  tumor  into  nodules  or 
surround  it  as  a  whole. 
Cartilage,  the  perichon- 
drinm,  endosteum,  perios- 
teum, and  different  forms 
of  connective  tissue  may 
form  the  matrix  of  enchon- 
dromata.  Those  arising 
from  cartilage  or  bone  are 

known  as  ecchondroses.  ! 

The  tissue  of  enchondromata  very  frequently  suffers  retrogressive  meta. 

morphoses.     The  ground-substance  in  large  tumors  shows  a  tendency  tc 

undergo  in  areas  a  mucoid  degeneration  and  liquefaction.     This  may  leac' 


^ff0^r 


'\ 


■<?■; 


^-     "^       ■'^     s,     S.-= 


Fig.  2o(.— Chondromyxosarcomaparotidis  (alcohol,  carmine); 
fl.  Cartilage;  />,  sarcomatous  tissue:  c,  myxomatous  tissue;  d 
cartilage  in  process  of  liquefaction  and  being  converted  int' 
sarcomatous  and  myxomatous  tissue.     X  S\). 


V'^ 


e  ^ 


ho.  258.-Periosteal  cbuudroiua  of  ihu  calouiiuiis,  witU  areas  of  calciflcatiou  (xMiUler'>  liuid,  iKernatoxylir 
a.  Hyaline  cartilage ;  b,  c,  calcified  cartilage.    X  Zi.% 


I 


CIIONDKO.MA.  393 

itlier to  tlio  formation  of  mucous Hskiic  {V\'^.  -~u,  r),  lluis  <;ivlii.i;  rise  loa 
fiond roin if.ro i)K( ;  or  to  a  total  liquetaclioii  of  llic  j;rouii(l-suI)staii('«' willi 
estructioii  of  the  cells,  thus  formiug  degeneration -ci/nIs  containiiii;-  fluid. 


259.— Osteophonrlriiiiii    -i   m,    iiiimktus  (alcohol,  picric  acid,  liaMnatDxyliii,  cariiiinc).    <(,  Hyalinecar- 
tUage;  7),  bone  ;  c,  caitilaiii'  wliicli  is  becoming  converted  into  lumi; ;  ((,  blood-vessel.     X  2.50. 

I  Other  cases  the  cartilage  may  become  calcified  (Fig.  258,  h,  e),  or 
lie  bone  may  be  formed  (Fig  259,  e,  h),  so  that  the  tumor  must  1)6 
rmed  au  osteochondroma.  Through  a  marked  proliferalion  of  the 
irtilage  cells  sarcomatous  tissue  may  be  developed,  the  tumor  becom- 
ig  changed  to  a  chondrosarcoma  (Fig.  257,  &). 

The  euchondromata  are,  on  the  whole,  benign  tumors,  although 
etastases  may  occur  following  a  rupture  into  a  lymph-  or  blood -\essel. 

In  the  region  of  llie  spheno-occipital  suture,  in  the  mc(li:in  line  of  the  clivus,  tlicre 
not  infrciiuentlv  found  a  small  tumor  which  has  been  designated  ecchondrosis  phy- 
ilifera  sphenooccipitalis  (  Virchow).  It  either  lies  beneath  the  dura,  or  at  its  higli- 
t  point  breaks  through  this  membrane  and  penetrates  into  the  arachnoid  and  pia.  In 
i  typical  form  the  fumor  consists  of  bladder-like  cells,  resembling  plant-cc-Ils;  and 
kes  its  origin  partly  from  the  bone-marrow,  partly  from  the  surface  of  the  bone, 
irtilage  and  bone  tissue  maybe  associated  with  the  jieculiar  tumor  tissue,  and  for  this 
ason  VirchoiD  regarded  the  growth  as  a  chondroma  arising  from  remains  of  the 
heno-occipiral  ca'rlilaue  and  characterized  l)y  a  peculiar  vacuolar  degeneration  of  the 
lis.  The  peculiar  cliaracter  of  the  tissue,  Jiowever,  favors  tiie  view  advanced  by  //. 
uller,  and  recently  supported  by  Jiihlxrt,  that  the  growth  is  a  product  of  a  prolifera- 
te activity  of  remains  of  the  chorda  (c^/YZ6>7?ia).  It  is  probable  that  it  is  only  a  i)e- 
liar  chondroma  developing  from  the  endosteum  or  periosteum. 

Literature. 

:  (^Chondroma.) 

^neke:  Chomlrom.     Bibliothek  d.  med.  AViss.  v.  Drasclie,  Wien.  1000. 
■  Biesiadecki ;  ]\Icfastas(  nhildung.     Sitzuim:sher.  d.  Wiener  Akad..  .wii. 
•rch-Hirschfeld:  Zur  Casuistik  der  Geschwulslembolie.     Arcli.  il.  lb-ilk. ,  .\.,  ISOO. 
:Dembowski:  (  hondro-Endotheliome.     Zeitsclir.  f.  Chir.,  -.Vl  I'.d.,  \x'M. 
|ust:    Ungew.   Verbreitung  e.   Knorpelgeschw.   i.   d.   JJlulbahn.     IJi'Ur.   v.  Ziegler. 
xxviii..  1900. 


394  TUMORS. 


Francois:  Contrih.  a  I'ot.  d.  I'encliondr.  dii  bassin.     These  de  Paris,  1876. 

Kast  u.  V.  Reckling-hausen :  Ein  Fall  von  Enchondrom  mit  ungewoliuliclieu  Mv' 

plicatiouen  (Coinbinatiou  mit  Cavernoni).     Vircli.  Arch.,  118  Bd.,  1889. 
Klebs:  Euchondrosis  sphenooccipitalis  amylacea.     Vircli.  Arch.,  31  Bd.,  1864. 
Kiittner:  Geschwulste  d.  Submaxillaris.     Beitr.  v.  Bruns,  xvi.,  1896  (Lit.). 
Lesser:  Enchondroma  osteoides  mixtum  der  Lunge.     Virch.  Arch.,  69  Bd.,  1877. 
Nebelthau:  Gallertgeschw.  d.  Clivus  Blumenbaclii.     Inaug.-Diss.,  Marburg,  1897.; 
Paget:  Metastasenbildung.     Med.-Chir.  Transact.,  xxxviii.,  1885. 
Ribbert:    Ekchoudrosis  physalifera  sphenooccipitalis.      Cbl.  f.  allg.  Path.,  v.,  1 

(Lit.);  Exper.  Erzeugung  eiuer  Ekchondrosis  physalifera.     Verb.  d.  XIIL  Coi 

f.  inn.  Med.,  1895. 
ScMapfer,  E. :  Das  Rippenchondrom,  Leipzig,  1881. 

Steudel:  Multiple  Ekchondrome.     Beitr.  v.  Bruns,  viii.,  1891.  ' 

Virchow:    Die  krankli.   Geschwulste,   i.,   Berlin,   1863;    Monatsber,   d.   K.   Akad.l. 

Wiss.  zu  Berlin,  1875;  Deutsche  Klin.,  1884. 
Volkmann:  Endotheliale  Geschwulste.     Zeitschr.  f.  Chir.,  41  Bd.,  1897  (Lit.).        ' 
Wagner:  Zur  Casuistik  des  Enchondroms.     Arch.  d.  Heilk.,  ii.,  1861.  j 

Wartmann:  Rech.  sur  I'enchondrome,  Paris,  1880  (Lit.).  | 

Weber:    Exostosen  u.  Enchondrosen,  Bonn,   1856;   Zur  Geschichte  d.  Enchondrca, 

namentl.  in  Bez.  auf  heredit.  Vorkommen  u.  secundare  Verbreitung.     Viich.  ArL 

35  Bd.,  1866.  ' 

Zeroni:   Entwickelung  d.  Enchondroms  d.  Knochen.     Arb.  a.  d.   path.   Inst,  zu  Ct- 

tingen,  1893.  \ 

(e)  Osteoma.  I 

§  106.  The  term  osteoma  is  applied  to  tumors  which  consist  of  osstiis 
tissue.  Such  growths  arise  chiefly  from  the  boues  of  the  skeleton  (F'i. 
2G0-2G2),  but  may  develop  elsewhere.  j 

The  new-growths  of  bone  arising  in  connection  with  the  skeleton  hj'e 
been  variously  designated  according  to  their  location  and  relations.  A. 
small  circumscribed  new-growth  of  bone  attached  to  old  bone  is  ca:rti 
an  osteophyte;  when  of  a  larger  size  and  more  tumor-like,  •<in  exostd^. 
Circumscribed  formations  of  bone  inside  of  bones  are  known  as  enostG\s. 
New-growths  of  bone  not  attached  to  old  bone  are  classed  as  follo!?: 
movable  periosteal  exostoses,  which  have  their  seat  in  the  periosteum  'it 
are  separated  from  the 
bone ;  parosteal  osteomata, 
lying  near  the  bone;  dis- 
connected osteomata,  which 
are  situated  some  distance 
from  the  bone,  in  the 
muscles  and  tendons ; 
and,  finally,  heteroplastic 
osteomata,  which  occur  in 
other  organs,  as,  for  ex- 
ample, in  the  lungs,  mu- 
cous membrane  of  the 
trachea,  in  the  skin,  arte- 
ries, mamma,  etc. 

Excrescences  on  the 
teeth,  consisting  of  ce- 
ment -  substance,    are 

known      as     dental      OSteO-        F,c.ooo._ivory-like  exostosis  ofthe  parietal  bone.    Natura  ze. 

mata ;  those  consisting  of  ; 

dentine,  as  odontomata. 

According  to  their  structure,  osteomata  may  be  divided  into  har;Or 
eburneous  osteomata,  (osteoma  durum  or  eburneum)  (Figs.  260  and  I.'), 
and  softer  sponyy  forms  (osteoma  spongiosum  or  medullare)  (Figs.  261  ;ia 


OSTEOMA. 


:w 


263).       Tho   former   consist    of  linn.    (•()in])a('t   tissue   like   that  of   tlj(> 

cortical   ])(>itioii   of  the   loii^-  bones,  and   ])ossess  very  narrow  nutrient 

canals  (Fly.  LMi2,  a);  the  latter  are  nuule  up  of  narrow,  delicate  bony 

trabecuhe  and  wide  medullary  spaces  (Fig,  2();i),  and  resendjle  spon},'y 

bone  in  structure. 

!        The  surface  is  sometimes  regular  and  snn)oth,  so  tlint  the  whoh'  tumor 

I  presents  the  form  of  a  cone  (Fig.  200),  or  of  a  spline,  or  a  pedunculated 

I  button;  or  it  may  be  irregular,    rough,   and  nodular,   without  delinite 

'  resemblance  to  any  given  form  (Fig.  2<)I).     The  lirst  variety  occurs  ])ar- 

ticularly  in  the  eburneous  forms,  which  are   found  most  fretpifiitly  as 

exostoses  njjon  the  skull  ( I'Mgs. 
2G0  and  2<)2);  the  latter  in  the 
spongy  exostoses  and  the  dis- 
connected and  hetei-oi)lastic 
osteomata,  such  as  are  found, 
for  example,  in  the  falx  of  the 
dura  nniter  (Fig.  2G;{). 

Osteomata  may  occur  as 
sinr/lc  or  multiple  tumors,  the 
latter  mode  of  occurrence  being 
relatively  common.  The  i\-oi-y- 
like  exostoses  of  the  cianinm 
and  the  osteomata  of  llu'  dura 
mater  are  very  fre(|uently  of 
multiple  occurrence,  and  circumscril)ed  bony 
growths  often  appear  in  great  numbers  on 
the  bones  of  the  extremities  and  truidc.  In 
such  cases  the  epiphyseal  ends  of  the  bones 
and  the  points  of  insertion  of  tendons,  or 
both  at  the  same  time,  are  the  favoi-ite  seats 
of  development.  It  is  probable  that  such 
growths  are  to  be  referred  to  an  inherited 
predisposition  of  the  part  adVcted  \o  o\er- 
growth,  or  to  disturbances  in  the  de\-elo])ment 
of  the  skeleton.  At  times  a  hei-editaiy  fac- 
tor can  be  demonstrated.  The  bony  plates 
and  spicules,  Avhich  in  rare  cases  (le\clti|)  in 
the  lung  or  in  the  mucous  membrane  (»f  the 
air-passages,  may  also  occnr  in  huge  nnnd)ers. 
The  developiiieiit  of  tlie  bone  takes  ]>lace 
partly  through  the  formation  of  osteoblasts, 
as  described  in  §  83,  and  partly  through  metai)lasia  of  formed  ti.ssues 
(§  88).  The  matrix  is  formed  chiefly  from  the  connective  tissue  of  the 
periosteum,  as  well  as  that  of  the  tissue  from  which  tlu^  osteoma  aris<'s; 
and  also  from  that  of  the  perichondrium  andeiulosteum.  If  an  exostosis 
develops  in  such  a  nninner  that  cartilage  is  liist  formed  from  the  prolif- 
erating ])eiiosteum  or  bone-marrow,  and  fiom  this  caitilage  bone  is  later 
develoix'd,  it  is  called  a  r(ir(i/(if/iit(>ii.sr'.rosf(>.sis  (Fig.  2<il  ) ;  when  the  exos- 
tosis is  fornu'd  directly  from  tlie  i)rol iterating  i)eriosteum  without  an  in- 
termediate stage  of  cartilage,  it  is  known  as  a  coinirrtin'-tin.sur  r.nt.sto.sin 
(Figs.  2(j(),  2f)2,  and  203). 

The  combination  of  connective  tissue  and  I»one  in  a  lunior.  in  Mich  a 
manner  that  the  connective  tissue  repies<Mits  a  chief  consliliieni  of  the 
growtli  and  does  not  simply  represent  the  i)eriosteum  and  boMc-manow 


Fig.  261.— Exostosis  oartilaginea 
of  the  upper  diaphysis  of  the  tibia. 
Reduced  about  one-half. 


396 


TUMORS. 


of  the  bone,  gives  rise  to  an  osteofibroma.     This  is  a  very  commor 
tumor  of  the  osseous  system.     The  abundant  production  of  bone  in  2 


c-'  .^ 


Fig.  263.— Ivory-like  osteoma  of  the  parietal  bone,  seen  in  frontal  section,    a,  Osteoma;  b,  skull-cap' 
Eight-ninths  natural  size.  1 

chondroma  leads  to  the  formation  of  an  osteochondroma  (Figs.  259  amj 
264);  these  tumors  are  lilcewise  usually  found  in  the  long  bones.     Th(j 


Fig.  263.— Osteoma  of  the  dura  mater  (alcohol,  picric  acid.  ha?matoxyIiu,  carmine) .    X  40. 


OSTEOMA. 


39; 


new-growth  may  develop  in  the  periosteuin  (V\ix.  '-*<;i,  <■)  cr  in  ii„» 
endosteum  (a,  b).  An  abundant  formation  ol"  l)oi'i\  t  i;il)c(  iil;i"  (  /",  /,,  k) 
in  the  cartilage  (r,  r/,  i)  ijivos  to  tlie  tissue  a  linn,  liaid  consislcnec 

:\[auy  of  the  uew-orowtlis  of  Ivoue  whicli  coine  under  ol)s«'iva1ion  are 
not  tumors  in  the  strict  sense  of  the  term,  but  are  maIf<»rm:ilions  of  the 
skeleton  or  hyperplasias  residting  from  excessive  growtli  or  from  intlam- 
matory  processes. 
This  is  ti'ue  particu- 
larly of  many  osteo- 
phytes and  exostoses, 
and  also  in  part  of 
the  parostoses  and  the 
disconnected  osteo- 
mata  (bone  forma- 
tionsiu  lympli-glands 
and  lungs).  The 
bony  plates  not  in- 
frequently found  iu 
the  falx  of  the  dura, 
and  which  have  a  uor- 
mal  bone -marrow 
(Fig.  263),  are  to  be 
regarded  as  misplaced 
portions  of  the  skele- 
ton. The  formations 
of  bone  known  as 
nder\s  bone  and  driJI- 
bone,  which  are  found 
in  the  adductors  of 
the  thigh  and  in  the 
deltoid  muscle,  as  the 
result  of  riding  and 
the  repeated  shoid- 
dering  of  arms,  are 
to  be  regarded  as  tu- 
mors, which  develop 
from  a  congmiUd  anlar/e,  in  that  the  connective  tissue  of  the  niuscTe 
shows  characteristics  which  oidinarily  belong  only  to  the  periosteum 
and  bone-marrow.  The  so-called  nij/o.sifis  os.sijinoi.s—n  ]ieculiar  disease 
of  the  muscles,  characterized  by  a  progiessive  ossilicat ion  of  their  eou- 
nective  tissue  during  childhood — is  to  be  similarly  interpreted. 


Fig.  264— Osteochondroma  of  the  humerus  (alcohol,  picric  acid,  hi^ 
matoxylin,  carmine).  «.  Cortical  portinn  of  the  liuiiicrus;  /).  medul- 
lary cavity;  c,  periosteal  deposit  of  boin' ;  </,  iKniiiiil  Haversian  canals; 
e,  dilated  Haversian  caiiMls  tilled  with  eiiriil:u.'e,  coniaininjr  newly 
formed  bone  at /;  ;/,  eartilMRe  with  lione-tralieiuhe /i,  f(jrmed  by  the 
periosteum;  1,  cartilage  with  newly  formed  bone-trabeculie,  nrlsing 
from  the  endosteum  ;  /,,  /.  old  bone  trabeculae;  m,  remains  of  murrow- 
tlssue.     Pocket-lens  magniUcation. 


Literature. 

(O.sfroinii.) 

Arnold,  J.:  Osteome  der  Stirnhohlen.     Vircli.  Aifli.,  57  Rd..  1873 
Arnsperger:  Ivnoclienbildun^' in  der  Ltiiige.     licitr.  v.  Zieglcr,  xxi.,  1897. 
Benjamin-  Kuoclieimesfhwulst  iin  Geliirii.     Yircli.  Arcli  ,  14  Bd.,  IH.IH. 
Chiari:  .Multiple  Exostosen.     Prag.  nicd.  Wocii.,  1892. 

Cohn:  Dilliise  Kiiochenbildung  iu  der  Luntro.     Viirli.  Aicii.,  101  IM.,  ISH.!. 
Colinheim:  Mtdtiple  E.xostosen.     Virch.  Arch.,  38  Bd.,  18(37. 

Dennig:    Ueber  Knoclienbilduiig  in  der  Trachealschieindiaiit.     Px  itr.  v.   Zicgk-r,  iL, 
ISMS. 

De  Witt:  Myositis  Cssilicans.     Anier.  Jour,  of  Med.  Sc.  1900  (Lit.). 
Ebstein:  Osteom  der  1.  Kleiiihindiemispliilre.     Yirch.  Arch..  49  Hd..  1870. 
Forster;  Verjistigte  Knociieiibildung  in  der  bunge.     Yirch.  Arch.,  18  Bd.,  1858. 
Heuking:  Multiple  E.xostoseu.     Yirch.  Arch.,  77  Bd..  1879. 


398 


TUMORS. 


fleymann:  Ilereditare  multipie  Exostosen.     Virch.  Arch.,  104  Bd.,  1886. 

Huber:  Multiple  Exostosen.     Virch.  Arch.,  88  Bd.,  1883. 

Lenhossek:    Knorpeliihuliche  u.  wahre  Knocheubildung  im  Penis.     Virch   Arch    60 

B(i.,  1874. 
Meschede:  Osteom  des  Grosshirns.     Virch.  Arch.,  35  Bd.,  1866. 
Mischnikofif:    Kuochenbildung  in  der  Trachealschleimhaut.      Inaug.-Diss.,   Zurich 

181)4. 
Neumann,  E. :  Osteom  des  Hodens.    Arch.  d.  Heilk.,  1875.  j 

V.  Reckling-hausen :  Ein  Full  vou  multiplen  Exostosen.     Virch.  Arch.,  35  Bd.,  1866.' 
Reinecke:  Erblichkcit  multipler  Wachsthumsexostosen.     Beitr.  v.  Bruns,  vii.,  1891. 
Spengler:  Ueber  die  Erblichkcit  multipler  Exostosen,  Strassburg,  1887. 
Steudener:  Osteome  der  Trachea.     Virch.  Arch.,  42  Bd.,  1868. 

Virchow:  Die  krankhaften  Gescliwiilste,  ii.,  1865.  ' 

Weber,  O. :  Exostosen  u.  Enchondrome,  Bonn,  1856. 

(/)  Hiemangioma  and  LympJiangioma.  , 

§  107.  Under  the  term  angioma  are  grouped  those  tumor -like  forma-\ 
Uons  in  the  structure  of  which  blood-vessels  or  lymph-vessels  constitute  such  ari\ 
imjyortant  j)art  as  to  determine  the  character  of  the  tumor.  I 

Vascular  tumors  arising  from  blood-vessels  are  called  hsemangiomata.i 
or  angiomata  iu  the  restricted  sense  of  the  term;  those  arising  from! 
lymph- vessels  are  designated  lymphangiomata.  Such  tumors  for  tht! 
greater  part  represent  formations  which  may  be  regarded  as  malfo^-ma-^ 
tions  of  a  more  or  less  extensive  vascular  area.  Of  the  hcemaugiomatri 
there  may  be  distinguished  four  chief  varieties:  hcemangioma  simplex,' 
hcemangioma cavernosum,  hcemangiomahypertrophicum,  and  angioma  arteriole 
racemosum.  \ 

A  haemangioma  simplex  or  teleangiectasia  is  a  tissue-formation  ii; 
which,  within  a  ground  tissue  of  normal  occurrence  in  the  body,  there  hi 


Fig.  205.— Teleangiectasis  of  the  panniculiis  adiposus  of  the  abdominal  wall  (formalin,  haematoxylin,  eosin ' 

o,  IMood-vessels  tilled  with  blood  ;  h,  adipose  tissue.     X  80.  | 


found  an  abnormal  increase  in  the  number  or  in  the  size  of  the  capillaries  an, 
veins,  whose  structure  in  part  is  essentially  changed. 

Such  formations  occur  most  frequently  in  the  skin  and  subcutaneou 
tissue.  They  are  usually  congenital,  but  increase  in  size  after  birtl 
They  are  designated  vascular  naevi,  and  are  often  found  in   placf; 


I 


lI.EAIAXGIOMA    AND    LVM  IM  I  A  \(  i  I(  )M  A 


399 


here  fetal  elefts  have  closed  (Jissiini]  <iii</inma(a).  Of  a  tumor  in  the 
•dinary  sense  it  is  often  seareely  possible  to  speak,  sinee  tlie  skin  may 
j.ow  no  tunun-like  elevation.      On  the  othei-  hand,  there  oecnr  e\tcnsi\e 


^ 


-Dilated  capillaries  of 


teleanpriectatic  tumor  of  the  brain.  Isolated  f nun  a  P'tI ion  of  tumor  by 
means  of  shaking.    X  300. 


eangiectases  of  the  skin  and  snbcntaneons  tissue,  ]>reseiitin;;-  either  as 

eumscribed  growtlis  or  as  flat,  occasionally  nodular  thickenings  of  the 

fjin,  which  may  with  propriety  be  termed  tunn)rs.     The  smooth  inrnis 

nilosus,  on  the  other  hand,  ai)i)ears  as  an  extensi\esni)erticial  substitu- 

>n  of  the  skin  by  another  tissue.     Tlie  color  of  the  atfected  jxution  of 

fe  skin  is  either  bright  red  (nicvus  flammev.s)  or  hfid.sli-rrd  (iKfi-Ks  riiiasits). 

le  line  of  demarcation  between  the  normal  and  allccted  skin  is  nsu- 

'  ally  not   a  shar]>   one ; 

around  the  edg<'  and  in 
the  neighborhood  of 
the  chief  ai«'a  of  dis- 
coloration there  are 
often  found  little,  cir- 
(UiMserilH'd  retl  spots 
appearing  as  <tutrun- 
ners  of  tlm  ]n«>cess. 

The  i('(l  color  is  due 
to    the    dilated    blood- 
vessels wlii(  II  ai«'  sil  u- 
.ited  i'ither  in  the  cor- 
n  or  in  the  subcutaneous  fat  tissue  (Fig.  I'^i"),  a);  and  cases  occur  in 
^'ich  large  areas  of  the  subcutaneous  adipose  tissue  prcsnit  a  red  aj»- 
Iiraoce  as  a  result  of  the  pathological  developnu-nl  of  blood-\»-ssels. 


•  2fi7.- Angioma  cavemosum  cutaneum  conKenituin  (MOller's 
liipmatoxylln;,  a.  Epidermis;  ?j,  cerium;  c,  cavernous  blwd- 
s.    x-M. 


400 


TUMORS. 


More  rarely  thau  in  the  skin  and  snbcutaueons  tissues,  there  occur  s'J 
ilar  augiomata  in  other  jjlaces:  in  glands  (mamma),  bones,  brain  (]g, 
266),  and  spinal  cord  and  their  membranes.  Not  infrequently,  ouke 
other  hand,  there  are  found  analogous  vascular  changes  in  tumors,  ,s. 
for  example,  in  giiomata  or  sarcomata.  ! 

If  the  A-essels,  which  are  usually  abnormally  abundant,  are  isola  li, 
it  becomes  evident  that  the  capillaries,  or  also  the  small  veins  {angiha 
simplex  vcnosum),  are  more  or  less  dilated.  These  dilatations  (J!^. 
266)  are  either  spindle-shaped  or  cylindrical,  but  may  be  saccula  )r 
spherical,  and  the  difterent  forms  of  dilatation  may  be  combined  in  jie 
greatest  A'ariety  of  ways.     The  dilated  blood-vessels  are  united  Ath 


ym  'J 


Fig.  2()S— Aiiirioiua  (a\uiiu'5Uiu  htpatis.  (MuUorN  fluid,  luLiijato\jlm,  tosin).    o,  Luer  tissue;  b.tigl- 

onid.     >   100  ' 

each  other  by  capillaries  of  normal  size  or  of  moderately  increased  |li- 
bre.  The  walls  of  the  vessels  are  thin — that  is,  in  comparison  with  :)r- 
mal  capillaries  they  are  but  slightly  thickened.  ' 

A  haemangioma  cavernosum  or  tumor  cavcrnosus  is  a  vas{\ar 
tumor  consisting  essentially  of  a  cavernous  spongy  tissue,  whose  striiclre 
suggests  that  of  the  corpus  cavernosum  or  spongiosum  of  the  penis  (1!,'S. 
267  and  268).  Through  the  filling  of  the  spaces  with  blood  these  tini)^ 
present  a  bluish-red  or  dark  red   lolor.  ;_ 

The  cavernous  angioma,  like  :he  angioma  simplex,  occurs  chief'in 
the  skin  (Fig.  267,  c)  and  subcu  i,neous  tissues,  where  during  the  p(|od 
of  development  it  appears  as  a  pathological  formation  of  the  vas(|ar 
system.  At  times  it  forms  only  a  small  bluish-red  spot  {ncevus  vascu^ 
vi7iosus) ;  at  other  times,  a  smooth,  elevated  (Fig.  267),  or  sli#y 
nodular  bluish-red  M-art  (meims  vasculosiis  j))-ominens,  verruca  vascul})', 
or,  finally,  a  circumscribed  bluish-red  discoloration  or  thickening  of  jhe 
skin.  In  the  event  of  an  extensive  development  of  cavernous  tissi;  in 
the  subcutaneous  or  intermuscular  connective  tissue,  there  may  r  jilt 


I 


h.i:ma\(;i().ma, 


401 


I  Jarf/e  tumors  atul   elej)h(niti(isi,s-Jih<-  (lisiii/nniliiui.s    <>/  jtorfimis    of  l/ir    Imdi/ 
{^eiephatiiiasis  hivmaiu/ioindfofio). 

Witliin  the  body  the  eavenious  lui^iouiii  is  round    nmsi   (•oimiiniily 
iu  the  liver  (Fig.   2G8,  a,   b),  but  may  develop  als<i   in    otlirr   oigaiis: 


Fio.  269.— Angioma  simplex  hypertrophicum  (formalin,  ha?matnxylin).    a.  Vessels  rontalnini?  blood;  /», 
empty  and  collapsed  thick-walled  blood-vessels  rich  in  nuclei.     X  KKI. 

kidney,  spleen,  intestine,  bladder,  bones,  ninseles,  uterus,  biaiii,  etc. 
In  the  liver  it  appears  in  the  form  of  dark-red  areas,  varying  in  si/.e 
from  that  of  a  pin-head  to  several  eentimetres  in  diametei-.  They  take 
the  place  of  the  liver  tissue,  and  are  not  elevated,  or  but  slightly,  above 
the  liver  surface. 

The  width  of  the  blood  spaces  and  the  thickness  of  the  tial»e<iihc 
rary  greatly  in  different  cases;  the  angioma  mny  in  portions  or  througli- 

out   be   compo.sed   of    iibrous   tissue, 
in  that  more  fibrous  tissue  was  formed 
in  the  beginning,  or  Iibrous  ]>rolilera- 
(.^^'•.      V  -^r-^^-'-t^-^j^^'^^j:)       tions  have  taken    ]>lace   hiter  as   s<'- 
\y'\     ■  -'^■■^^'^^}:')^h       qnehe  to  the  thromlx.sis.     The  blo(.<l 
^^-       '  '  V    "-^v..;^      -j>       vicic^'vi  Mil' lined  wit  l(  ciidotliclinui  ;  at 


'^  /,j     JV\       queue  to  tne  inromoosis.      ineniood 
^^"^'y^^   JJ^      Spaces  are  lined  wit  ii  eiidothelinm  ;  at 
\    ''\ -w  ^^;P      limes   smooth    mnsch'-liltiu'S   may    Im- 


b^   . 


^r:%: 


K^m^'^^^^m^ 


demonstrated  in  thcii-  wails,  and  tiic 
?  interstitial  tissue  is  often  rich  in  elas- 
9  tie  fibres  (IJriichanow).  The  tumor 
]  is  usually  sharply  outlined  from  tin* 
{  neighboring  struct ures  by  conn«'<-tivr 
r        tissue.      rsually    no     li\«'r     cells    are 

found   in   t  lie  t  iMbcciilic.  but   vaiirlies 

F.o.-.rO.    Ann..ma  simpu.x  hvp.rtrophicnm        «!<•    <""'""'-    '"  Nvl' '«•!'.  ^.e    latter  in    part 

jtaneiiiii  .t  .siihiiitiiii.iiiM  (iiicohoi,  .aniiiii.i.      <«nclose    sucli,  and   ill   wiiicli,  lurllier, 

1  Iliciiiidcllp  of  Uii-  s.Mliiiii  is  Ihi-  duct  of  a        ^,         ,  ,         ,  ,  .  .i    «i ,„,o^. 

veat-piiind  cut  tn.n.sv.i>..iy.    ,   x'od.  the  blood  s|)aces  hcie  aiid  tlieie   jtass 

over    into   llic    li\t'i- «-:ii»ill:iri«'s.    siicli 
coinmnnication  ordinarily  not  taking  |>l:icc. 

Thecavernousangiomaof  the  liver  occurs  in  old  individuals,  andals(» 
a  infants  and  children  of  different  ages,  and  not  infreipiently  is  of  mul- 


402 


TUMORS. 


tiple  occurrence.  It  is  probably  caused  by  a  local  disturbance  of  de 
velopment,  which  proceeds  from  tlie  vessels  of  Glisson's  capsule  or  fron! 
the  iutra-acinous  capillaries;  and  is  characterized  by  an  abnormal  de- 
A'elopment  of  the  blood-vessels  at  the  expense  of  the  other  tissues.  The 
growth  is  slow  and  limited ;  ordinarily  the  liver-cells  in  the  immediatt 
neighborhood  show  no  signs  of  degeneration.  During  the  period  of  rapic 
growth  (Briichanow),  there  may  occasionally  be  demonstrated  in  childrei; 
the  presence  at  the  periphery  of  the  growth  of  a  cellular  granulation  tis^ 
sue,  in  which  the  blood-vessels  consist  of  delicate  endothelial  tubes  hav 
iug  a  narrow  lumen. 

The  hasmangioma  hypertrophicum,  in  its  most  typical  form  {Imman', 
gioma  simplex  lujpcftrophicn in),  occurs  most  frequently  in  the  skin  am, 
subcutaneous  tissues,  where  it  forms  circumscribed  nodules  similar  ii 
part  to  the  soft,  smooth  warts.  The  pathologically  altered  vessels  ma;>i 
lie  iu  the  papillfe  and  corium  as  well  as  in  the  subcutaneous  tissue,  auci 
eitlier  form  narrow  tubes  tilled  with,  blood  (Figs.  269,  a,  and  270),  th(j 


Fig.  271.— Angioma  cavernosum  hypertrophicum  (angioendothelioma)  of  the  skull-cap  (MiiUer's  flu 
ha?matoxylin).  a.  Blood-vessel  with  flattened  endothelium;  Z),  blood-vessel  with  cubical  and  cyhndri. 
endothelium.     X  250. 


walls  of  which  are  more  or  less  thickened  and  abnormally  cellular,  • 
else  solid  cords  of  cells  (Fig.  260,  h),  which  are  either  collapsed,  thiC' 
walled  vessels,  or  possess  no  lumen  whatever. 

In  very  rare  cases  it  happens  that  in  angioinata,  which  from  the  en- 
bre  of  the  vessels  bear  the  character  of  cavernous  angiomata,  there  occi » 
a  hypertrophy  of  the  vessel- walls;  and  this  hypertrox)hy  is  due  to  ti 
fact  that  the  flat  endothelial  cells  become  changed  into  cubical  al 
cylindrical  cells  (Fig.  271,  h).  Such  a  tumor  may  be  classed  as  ,i 
angioma  cavernosum  hypertrophicum,  or  as  a  hlood-vessel-enilotheJioma,  r 
hcemangioitic  endothelioma;  the  last  term  being  in  particular  applica ;' 
when,  as  a  result  of  the  marked  proliferation  and  multiplication  of  - 
endothelium,  there  are  produced  nests  of  large  cells  which  fill  up  e 
blood-vessels  (compare  Endothelioma,  §§  114  and  115). 

A  cirsoid  aneurism,  oi-  angioma  arteriale  racemosum,  or  angioa 
arteriale  plexiforme  (Fig.  272),  is  a  condition  in  which  the  arterie^"f 
an  entire  Aascular  area  are  dilated,  tortuous,  and  thickened,  so  that  ther  s 


I 


H.KMWCIO.MA. 


4():i 


foriiied  a  convolution  of  oularii<'(l  and  thickened  artci-ics.  'I'o  the  pnlpat  - 
iug  tiniicr  they  feci  like  a,  bunch  of  earth-worms.  .Many  of  llicse  an^io- 
mata,  ^vhicll   ocenr  paiticularly    upon    Ihe   liead,  and    whicii   jna\ canse 


■'/>; 


-Angioma  arteriale  plexiforme  arteri-.p  aii<:iili 


i-t  fniiitalis  (icxt.  ft,  sin. 


rosion  of  the  cranial  bones,  arise  from  conj;enital  anla^e;  otheis  ai)i)ear 

0  be  acquired,  and  develop  after  a  ti-aumatism,  but  it  is  possible  that 
pecial  conditions  may  liave  existed  befoie  th(;  trauma. 

Literature. 

(JIcviiiaiif/ioiiKi.) 

"■ppia:  Dos  tumeurs  .sanguines  erectilcs,  Paris.  1877. 

*neke:  Zur  Genese  dor  Lebcrangiome.     Vircli.  Arcli.,  119  IM,,  ls*K). 

riichanow:  Ililmangiom  der  Leber.     Zeit.  f.  Iloilk.,  x.\..  isill). 

urckhard:   Pathol.  Anat.  d,  cavernOsen  Angionis  dor  Leber.     biaiig.-Diss.,  AVllr/i- 

1  biirir.  ifs94. 

I'ibbern:  Ueber  Uussere  Angiome  (Zusamnienstellimg  v.  05  FilUoii).  Kiil,  IXfiit. 
jCeine:  Aiitrioma  art.  racem.  am  Kopfe.  Prag.  Vicrteijahrsst  lir..  iii..  iv.,  istii). 
jCildebrandt :    Ueber  multiple  cavernose  Angiome.     Dent.  Zi-itsclir.  f.  Chir.,  W  ]{d., 

1       INS!). 

Fjetschmann :  Uelicr  das  Angioma  arleriale  rac-emosnm.  Halle,  iss]. 

janghans:    IJcitrage  z.  Lehre  von  den  Gefassgeseliwiilsh'n.     \'ii(li.    .\n  li,,   T-'.  ]5d., 

I     1S7;». 

larkwald:  Intravasculilres  Endotheliom  d.  Kuochen.     Yin  li.  Ardi..  Ml  I!<1..  Is'J.i. 


404 


TUMORS. 


Mauclair  ct  de  Bovis:  Los  aniriomes,  Paris,  1896. 

Muscatello:  Angioiii  der  willkiirl  3Iuskeln.     Virch.  Arcb.,  135  Bd.,  1894. 

Nauwerck:  Hyperpkstisclics  Capillaiaugiom.     Virch.  Arch.,  Ill  Bd.,  1888. 

Pfeififer.  Ueber  Teleaugiektasie  u.  caveruose  Blutgescbwiilst,  Tilbiugeu,  1854. 

Reinbach:  Zur  Lebre  v.  d.  Hamorrboiden.     Beitr.  v.  Bruns,  xix.,  1897. 

Ribbert.  Wacbstbuni  u.  Genese  der  Angiome.     Vircb.  Arcb.,  151  Bd.,  1898. 

Schmieden:  Genese  d.  Lebercavernoms.     Vircb.  Arch.,  161  Bd.,  1900. 

Schneck:   L'eber  d.  Weseu  u.  d.  Entstebuug  des  Angioma  arteriale  racemosuni,  Berlin; 

18.S.5.  j 

Schrohe:  Teleangiektasieen  d.  Leber.     Vircb.  Arch.,  151  Bd.,  1898. 
Virchow:  Die  kraukbaften  Gescbwlilste,  iii. 
Wagner:  Das  arterielle  Rankenangiom  d.  oberen  Extreraitaten.     Beitr.  v.  Bruns,  xi  ^ 

1894  (Lit.). 
Weil:  Beitrage  zur  Kenntniss  der  Angioma,  Prag,  1877. 

yee  also  §  116.  j 


§  108.  Angioma  lymphaticum  or  lymphangioma  is  a  tumor  con 
posed  of  a  tissue  the  greater  part  of  which  is  made  up  of  dilated  hjmpi 
vessels.  The  following  different  forms  may  be  distinguished :  hjmphan 
gioma  simiylex  or  teleangiectasia  lym/phatica  (Fig.  273);  lymphangion 
cavernosuni  (Fig.  274);  lymphangioma  cystoides ;  and  lymphangioma  hypel 
trophicum.  The  cavities  of  these  tumors  usually  contain  a  clear,  ligh 
colored  lymph,  but  more  rarely  it  is  milky  and  contains  lymphocyte, 
mononuclear  and  polynuclear  leucocytes,  and  usually  also  eosinophil 
cells.  The  walls  consist  of  connective-tissue  trabecule  of  varying  tbic; 
ness  and  containing  more  or  less  involuntary  muscle ;  the  spaces  are  lin 
with  endothelium. 

In  the  lymphangioma  simplex  (Fig.  273)  the  lymph-vessels  of', 
more  or  less  extensive  area  are  dilated  and  their  walls  for  the  great  I' 
part  are  thickened.     In  the  cavernous  lymphangiomata  the  number  j: 


^ 


Fig.  273.— Weeping  subepithelial  lymphanarioma  of  the  skin  (alcohol,  carmine),    a,  Cerium  ;  h,  epithel 
t,  d,  lymph-spaces.    X  14. 

lymph-vessels  is  still  greater,  their  spaces  are  larger,  and  the  intervePg 
tissue  is  less  abundant,  so  that,  even  to  the  naked  eye,  the  tissue  pree^its  I 
a  spongy  appearance.     The  cystoid  lymphangiomata  contain  cysts  v  y 
iiig  in  size  from  that  of  a  pea  to  a  walnut.     The  tissue  between  1"' 
dilated  lymjih-vessels  consists,   according  to  the  location  of  the  tu  Ji-  i 
either  of  connective  tissue  (Fig.  273),  fat  tissue  (Fig.  274,  c),  muscl  or  , 
some  other  tissue.     At  times  nodes  of  lymphadenoid  tissue  may  b^u-  i 
closed  (e),  and  may  present  evidences  of  active  proliferation 


i 


LYMPHANXJIO.MA. 


405 


Lyiiipbaiit;iomata  are  sometimes  coii<i;enital ;  :it  ollici-  limes  llicy  make 
heir  tirst  appearance  at  a  later  period  of  life. 

The  coni;eiiital  forms  occur  particularly  as  dilVerciit  varieties  of 
!Ctasia  of  lymph-vessels,  and  are  found  cliielly  in  the  tonj;-ue  (iiiacro- 
jlossia),  palatal  arch,  lips  {iiKicrochcilid),  skin  {)i<rri(s  hiuiphutirus),  suh- 
'utaneons  tissue,  in  the  neck  {hi/f/roina  colli  con</(iiiti(tii),  vulva,  etc.  Tlu^ 
\i/mphait</ioiii((t<(  of  llw  shin  spread  over  moi-e  or  less  extensive  areas  of 
I  he  skin,  and  form  either  smooth  or  irre.i;ular  elevations  of  the  same.  If 
!he  blood-vessels  are  numerous  the  growth  juay  have  a  red  color.  The 
j-upture  of  dilated  lymph-vessels  lyinj;-  immediately  beneath  tlu'  ejdthe- 
iuui  (Fig.  273,  d)  may  give  rise  to  a  moist  condition  of  the  surface  and 


p:j,  ,.^-.^Tr^rj^m:p^'W^ 


IG.  274.— Lvmphangrioma  cavernosum  subrataneum  (alcohol,  alum-carmine),    a,  Ertatle  lymph-vessels; 
b,  connective  tissue ;  c,  adipose  tissue ;  d,  large  blood-vessels ;   c,  cellular  areas.    X  2(K). 


veutually  to  a  lympliorrhoea.  The  extension  of  the  cavernous  dexclop- 
lent  of  the  lymph-vessels  over  large  areas  of  the  skin  and  sulK'utaneons 
jissue  may  give  rise  to  chplKDitiasis-likr  disjif/untlion.s  of  the  ]r.\v\  alfected. 
ii'ot  infrecpiently  the  intervening  connecti\e  tissue  also  takes  ])art  in  the 
lypertrophic  growth,  or  there  develops  a  fibrous  elephantiasis  in  connec- 

ton  with  lymphangiectasia. 
In  rare  cases  chyle-containing  growths  (dijiUinfiionuiia)  are  found  in 
le  intestinal  wall  or  mesentery.      CyHiic  Jumpluinniomota  are  also  found 
pely  in  the  peritoneum,  as  pedicled  cysts. 

I  The  pathological  formations  which  may  be  classed  as  hypertrophic 
ymphangiomata  represent  peculiar  changes  of  the  skin,  MJiich  :ire 
jither  congenital  or  develop  in  early  youth.  They  are  coininoiily  known 
^  pigmented  moles,  lentigines,  freckles,  and  tleshy  warts. 

The  pir/mented  moles,  or  nccri pi f/nictdosi,  or  mel<tnom<d<i,  form  larger  or 
nailer  smooth  areas  which  are  not  ehnated  above  the  general  surface  of 
16  skin  (ncevHS  spilus),  or  prominent  wai-ty  growths  ()i(rni.s  prominem, 
!Bvm  vernicosus) .  When  covered  Avith  liair,  as  is  frecpiently  the  case, 
pey  are  called  hairy  moles  (nwvus  pilosiis).  In  color  they  are  usually 
ght  brown  or  dark  brown,  or  even  black  (Fig.  275) ;    and  are  usually 


40G 


TUMORS. 


covered  by  epidermis  of  normal  thick- 
ness, more  rarely  by  hypertrophic  epi- 
thelium. They  are  usually  small,  but 
may  be  as  large  as  the  palm  of  the  hand, 
or  under  certain  conditions  may  cover  a 
large  part  of  the  body  surface. 

Lentif/ines  appear  at  any  time  after 
birth,  and  upon  any  part  of  the  body 
surface ;  and  when  once  formed  they  re- 
main for  life.  They  form  sharply  cir- 
cumscribed yellow  to  brownish  -  black 
spots  closely  resembling  the  little  pig- 
mented nfBvi ;  and  vary  in  size  from  that 
of  a  pinhead  to  that  of  a  lentil. 

Freckles  or  ephelides  are  small,  irregu- 
larly outlined,  serrated,  pale-brown  spots, 
which  are  not  elevated  above  the  surface 
of  the  skin.  They  occur  in  young  indi- 
viduals, particularly  on  the  face,  hands, 
and  arms,  rarely  on  other  portions  of  the 
body ;  and  may  either  remain  i^ermanently 
or  disappear  after  a  longer  or  shorter 
time.  The  pigmentation  is  favored  by 
exposure  to  sunlight. 

Fleshy  moles  (verrucce  carnece)  are  non- 
ingmented,  circumscribed,  smooth  (Fig. 
276)  or  slightly  irregular,  or  more  rough 
and  papillary  (Fig.  278)  prominences  of 
the  skin,  over  which  the  epidermis  is  at 


Fig.  275.  —  Large  hairy  and  pigmen  I 

times   normal,   at   other  times  somewhat  ^S^^^^^^^I^^X^^\ 

hypertrophic  (Fig.    278,  a).  remaining  portions  of  the  body.      (Af: 

In  all    of   the   pathological    formations    ^'^""^'^     (Reduced  from  original.) 

just  described  the  connective-tissue  frame- 
work encloses    collections  of  cells,  either  in  round  or  cord-like  mass 
(Figs.  276,  277,  278,  ^7,  dj,  which  lie  partly  in  the  papillae  and  part, 
in  the  coriiun ;  and  are  the  more  abundant  the  more  the  growth  pi 


Tig.  276.— Lymphangioma  hyi)ertrophicum.    Seetion  through  a  small,  soft,  smooth  wart  (formalin,  li» 
toxylln,  eosin).    X  40. 


I 


T.TMPHAXCnOMA. 


v^'^ps^jS^:^.  '■vz\ 


^.  '^- 1 


407 


^«^tp. 


i^^'e 


Sfe 


^t..*^ 

^^a:??-. 


Fig.  277.— LyiuphanETioma   hypertnipliiinini.     lium 
iianuatoxylin,  ensin).    Sliarply 


^■W 


wart  {fdriiialin. 


jects  above  the  surface  of  the  skin,  lii  tlie  i)i,i,^in«'iit('(l  foims  (lie  (•♦•Us 
|i»f  the  cell-nests  may  also  contain  the  ])i.ininent  (chietly  in  the  form  of 
arown  or  yellow  granules,  but  in  pai't  dilfused  throughout,  the  substance 


^ -^ 


vM' — ^ 

I  .....I 


rf... 


'■Sk 


:» 


-''iS*iV;0Z^- 


.1 


Flo.  L^s.-Spction  throiiph  two  papilhe  of  a  papillary  m-sliy  wart  (alrohol.  carinliK-i.  n,  ThlrkrtHHl 
amy  layer  of  the  epidcriiiis ;  //,  t-pitlielial  [R'arls;  c,  rt'te  MalpiKlill ;  </,  m-sts  ami  xlniiids  of  (flls  In  Uio 
iplllae;  r/,,  ni-sts  and  strauds  of  cells  ia  tbe  reticular  layer;  t,  connective  tissue.    X  .'W. 


408  TUMORS. 

of  the  cells) ;  though  often  the  pigment  lies  chiefly  within  the  connec- 
tive tissue  cells  of  the  fibrous  portious  of  the  growth. 

The  cells  of  the  cell-nests  are  relatively  large  (Fig,  277),  possess  an 
abundant  protoplasm,  and  a  bright,  bladder-like  nucleus.     Their  posi- 
tion and  apijearauce  justify  the  assumption  that  they  represent  the  prod- 
ucts of  the  liroliferation  of  the  endothelial  cells  of  the  lymph-vessels.     In 
rarer  cases  similar  formations  arise  from  the  blood-vessels  (haimangioma 
hypertrophicum).     Accordingly,  it  would  seem  proper  to  class  these 
growths  with  the  endotheliomata  or  lymjihangiosarcomata,  but  their  lim-  ; 
ited  growth  makes  their  classification  as  lymphangiomata  more  appro-  : 
priate  (see  §  114).      The  cell-nests  of  the  hypertroi^hic  lymphangioma  ' 
may  in  part  spread  out  more  diffusely  through  the  tissues  (as  is  the  case  i 
with  the  hypertrophic  hsemangioma),  so  that  the  peculiar  structure  of  \ 
the  growth  may  be  lost.     In  rare  cases  there  may  develop  a  combination  j 
of  hypertrophic  lymphangioma  and  li^joma. 

Vnna,  Kromayer,  Delbanco,  and  Marcliand  hold  the  view  that  the  cell-nests  of  the  ; 
cellular  najvi  are  of  epithelial  origin,  and  represent  misplaced  portious  of  the  surface 
epithelium ;  and  Kromayer  goes  so  far  as  to  assume  a  metaplasia  of  epithelium  into  j 
connective  tissue.     Preparations  showing  the  first  stages  of  the  development  of  nsBvi  , 
are  not  accessible  to  me;  but  a  thorough  study  of  naevi  and  fleshy  warts  of  a  later  stage 
does  not  show  any  connection  between  the  cell-nests  and  the  epithelium ;   and  conse- 
quently I  hold  the  opinion — notwithstanding  the  investigations  of  the  above-named 
authors — that  the  view  given  above  in  the  text,  in  regard  to  these  ua;vi  and  fleshy  ' 
warts,  harmonizes  most  perfectly  with  their  anatomical  nature  and  clinical  behavior,  ' 
both  in  their  fully  developed  condition  as  well  as  when  they  undergo  a  transformation 
into  malignant  sarcomata.     That  in  individual  cases  the  cell-nests  lie  close  to  the  epi- 
thelium is  no  proof  of  a  genetic  relationship,  since  the  ordinary  Ij'mphangiomata  also 
lie  close  to  the  epithelium  (Fig.  273,  d).  j 

According  to  investigations  by  Jadassohn  and  Lanz  the  cellular  warts  can  be  trans-  j 
planted  from  one  individual  to  another  by  an  Intra-epidermoidal  inoculation  of  cell- 
masses. 

Literature. 

{Lymphangioma  and  Cellular  Ncevi. ) 

Arnold:  Zwei  Fiille  von  Hygroma  colli  congenitum.     Virch.  Arch.,  32  Bd.,  1865. 

Arnstein:  Zur  Casuistik  der  Makroglossie.     Virch.  Arch.,  54  Bd.,  1872. 

Bauer:  Endotheliale  Naevi.     Virch.  Arch.,  142  Bd.,  1896. 

Bayer:  Bedeut.   d.   Fettgewebes  f.   d.  Aufbau  d.   lymphat.   IMeubildungen.     Zeit.   f. 

llrilk.,  xii.,  1891. 
V.  Biesiadecki :  Untersuch.  aus  dem  pathol.  Institut.,  1872. 
Bircher:  Aetiol.  d.  Naevus  pilosus  (untergegangenes  Zwillingsgeschwister).     Arcli.  f 

Derm.,  41  Bd.,  1897. 
Bogoliubsky :  Die  Pigmentflecken  der  Haut.     Inaug.-Diss.,  Bern,  1887. 
Delbanco:  Epitliclialer  Naevus.     Monatsh.  f.  prakt.  Derm.,  xxii.,  1896. 
Demieville:  Ueber  Pigmentflecken  der  Haut.     Virch.  Arch.,  81  Bd.,  1880. 
Freudweiler:  Lymphang.  cystoides  cutis.     Arch.  f.  Derm.,  41  Bd.,  1897. 
Frobenius:  Ueber  einige  angeb.  Cystengeschwillste  des  Halses.     Beitr.  v.  Ziegler,  vi., 

ls,S9. 
Gaucher  et  Lacapere:  Lymphangiome  circonscrit.     Arch,  de  med.  exp.,  1900. 
Hebra  u.  Kaposi:  ilaiidb.  d.  Hautkrankh.,  ii.,  1872. 
Koster:  Ueb.   llvgroma  colli  congenitum.     Verb.   d.   Wiirzh.   phvs.-med.   Ges.,  iii  . 

1872. 
Kromayer:  Histogenese  d.  weichen  Hautuaevi.     Derm.  Zeitschr.,  1896;  Erwiderun- 

an  Kibbert.     Beitr.  v.  Ziegler,  xxii.,  1897. 
Kruse:  Ueber  das  Chylangioma  cavernosum.     Virch.  Arch.,  125  Bd.,  1891. 
Ktittner:  Intermittir.  Entziindung  d.  Lymphangiome.     Beitr.  v   Bruns,  xviii.,  1897. 
Langhans;  Lymphangiom  d.  unt.  Extremitat.     Virch.  Arch.,  75  Bd.,  1875. 
Lesser  u.  Beneke:    Lymphangioma  tuberosum  multiplex.     Virch.  Arch.,  123  Bd. 

1S91. 
V.  Lesser:  Lymphangioma  diffusum  multiplex.     Zeitschr.  f.  Chir.,  34  Bd.,  18£ 
Lion:  Lymiilicyslcn  d.  Ligam.  uteri  latum.     Virch.  Arch.,  144  Bd.,  1896  (Lit.) 
Loewenbacli:  Histogene.se  der  weichen  Naevi.     Virch.  Arch..  157  Bd..  1899. 


MYOMA. 


409 


,  1.SS7. 
Arcli.,  0()]5(i. 


18«. 


I 

Fasse:  UoIxt  Lymiiliiiiiirionu'.     Ljuig'jiihcck's  Arcli.,  34  IJd. 

urNieden:  Lyinpliaii,<;ioktasi(Miiil  l^yinpluinliagii'.     Vircli 

'innei':   L\  iiipiiaiiiiioiii.     Cbl.  i.  Cliir.,  hsso. 

.Plaunei-;  N'acvus  coiincuitus.     Vicrtcljalirsschr.  f.  Derm.  u.  Sypli.,  xiv.,  1887. 

.  Recklinghausen:  Dii;  uuiltiiilou  Fibroine  dcr  Haul,  Berlin,  1882. 

ieichel:  Anych.  Lyinpiiaugioma  cysticum.     Yircli.  Arch.,  40  Hd.,  18(i9. 

'.ibbert:  ^Val■hstlu^m  u.  Geuese  d.  Angioinc.     Viirli.  Airli.,  IT)!  Bd.,  1898. 

:,itschl:  Lyinpliangiome  d.  ISIuskcln.     Bcitr.  v.  Bniiis,  xv.,  18*^). 

,oth:  Hc'tropcritouoaU'S  cystisclirs  Lymitliansrionia,  Zliricli.  1880. 

achs:  Lyinpliaiigionie  am  Aiigc.     Biilr.  v.  Ziegler,  v.,  18811. 

amter:  Ucbcr  LyinpliangioiiK-  d(>r  ]\Iuiidlii)hle.     Langciilicck's  Aicli..  II  Pxl.,  18!)1. 

chmidt:  JU-itr.  z.  Kenutniss  d.  Lymphangiome.     Arch.  f.  Dcini..  wii  .  Issm). 

chultes:  DilTuse  Lymphangiombilduug  am  Obcrscheukd.     In,iiii;.-l)iss.,  Kiciburg, 

is!t4. 
teudener:  Cavernoscs  Lymphaugiom  dor  Conjunctiva.     Vircli.  Arch.,  ."iOBd.,  1874. 
tiles:  Kep.  of  a  Case  of  Cavernous  Lymphangioma  of  the  Forearm.     Edinb.  llosp. 

Ucp.,i.,  1893. 
nna:  Naeviu.  Nacvocarcinome.    Berl.  klin.  Woch.,  1893;  Vircli.  Arch..  14:5 Bd.,  189(5. 
ariot:'j!^ote  s.  1.  les.  de  la  peau  dans  la  melanodermic  congcn.     An  h.  dc  piiys.,  .\., 
,     1887. 

'irchow:  Die  krankh.  Gescliw.,  iii. ;  Hygroma  cysticum  glutacale  congcn.     Virch. 
!     Arch.,  102  Bd. 

''aelsch:  Lymphangioma  cutis  cj'sticum.     Arch.  f.  Derm.,  51  Bd.,  1!)0(). 
''eg-ner:  I'cber  Lymphangiome.     Arch.  f.  klin.  Chir.     v.  Langenbeck,  x.\.,  1877. 
''eich.selbaum :  Chylaugioma  cavernosum  des  Meseuteriums.     Virch.  Arch.,  64  Bd., 
(     1875. 

(g)  Myoma. 

§  109.  A  myoma  is  a  tumor  consisting  essentially  of  neidii  formed 
usde-fibrcs.  According  to  the  nature  of  the  muscular  elements,  myo- 
ata  are  divided  into  lehntiijomata  formed  of  unstripcd  muscle,  and  rhabdo- 
lijonuda  composed  of  striped  muscle. 

I  The  leiomyoma,  or  myoma  IwviceUuJare,  occurs  most  frequenlly  in  the 
lerus,  more  larely  in  the  tubes,  uterine  li«;aments,  labia  majora,  mus- 


FiG.  271).— Myom,a  of  the  utenis  (Miiller'.s  (liiid,  ha'iiiato.xylln,  eo.sin).    X  ■»»>. 

Claris  of  the  gastrointestinal  tract  and  urinary  pas.sag('s;  and  may  form 
^  lerical,  nodular  tumors  of  var>  ing  size.  In  larc  cases  it  is  fonnd  also 
i  the  skin  and  subcutaneous  ti.ssues,   forming  in   this  location  small 


410  TUMORS. 

nodules  occasionally  reaching  the  size  of  a  pigeon's  egg.  Leiomyomai 
occur  as  either  single  or  multiple  tumors;  and  may  appear  during  chile 
hood,  or  even  develop  under  certain  conditions  during  intrauterine  lii 
(Marc). 

In  muscular  organs  the  new-growth  proceeds  from  the  musculari 
and  forms  during  its  development  bundles  of  muscle-fibres  (Fig.  27 
which  are  interwoven  in  different  directions,  and  consequently  preseii 


i^^ii'^^^ 


''t-        \^'%iyrr.     ,-.' 


I|lw 


\v  i|  ;\ 


X^ir  -  /  \ 


li.i 


l^^A^A. 


Fi(  „so  — 'Vnjnomvomi  sill  utiiHuiii  d  rsi  ( ilcohol  h^E'nlatox^llrl  losin)  a  C  utrnous  blood  s- 
S(  Is  7  sti  inds  <  f  imistlt  tut  1  iif,itiKlm  ill\  ^  same  <  ut  trinsver'.el)  d  lojintitnt  tiism  e  ai  7 
w  ith  h>pertrophit  musculdns ,  /  groups  of  hiuphoid  tells     X  46 

in  sections  a  variety  of  pictures  according  to  the  directions  in  which  Je 
bundles  are  cut.  Myomata  of  the  uterus  may  contain  included  utei  e 
glands.  Those  developing  in  the  dorsal  wall  of  the  body  of  the  uteis 
and  near  the  angles  of  the  tubes,  or  in  the  inguinal  region,  may  contb 
a  varying  number  of  gland-tubules  which  arise  from  the  Wolffian  biiy 
(von  Eecklinghausen) ;  such  tumors  may  be  designated  adenomyom<ii. 
They  are  distinguished  from  the  ordinary  spherical  myomata  which  '.e 
sharply  circumscribed,  by  the  fact  that  their  boundaries  are  not  shai  y 
defined.  Eventually  some  of  the  glands  may  become  cystic  as  the  re:  It 
of  the  accumulation  of  secretions.  According  to  Eicker,  Pfannensll, 
and  others,  the  ordinary  uterine  myomata  as  well  as  those  of  the  vagi^U 
vault  may  also  contain  epithelial  tubes,  which  probably  owe  their  or  in 
to  inclusions  of  portions  of  the  duct  of  ]M tiller.  In  the  skin  and  sulja- 
laneous  tissue  the  new-formation  of  muscle-fibres  proceeds  in  the  .st 
place  from  the  muscularis  of  the  vessels  (Fig.  2S0),  which  thereby*- 
come  fhickened  (a),  and  at  the  same  time  give  rise  to  free  strand  of 
musck'-ldncs  (h).  A  pathological  new-formation  of  blood-vessels  ma  Je 
associated  with  that  of  muscle  (a),  so  that  tumors  arise  which  are  dt'g- 
mitcd  a nrjiomijomata  (Fig.  280).     According  to  observations  by  Jada&'pffl 


I 


MYOMA. 


411 


jaiul  others,  multiple  inyoni:il:i  of  tlio  skin  may  lak,.  tlH'ir  mi-in  citlirr 
[Ironi  tlioarrectorcs  piloiuiii  or  fi'omtlio  inusclccclls  of  t  lie  sweat  ulaiids. 
j  A  certaiu  ainoiiiit  of  comicclivo  1  issue  always  takes  i)ait  in  tiie  for- 
liiiation  of  ;i  larue  myoma,  and  tifteii  assiniies  sneii  ini|»(titanee  tiial  the 
.tunun-  may  willi  piopriely  be  ealled  a  fibromyoma  or  myotibroma.  I'm- 
"xaini)le,  the  majority  of  the  uterine  myomata  aic  (il»i«»in.\(iniata.  Thc! 
ilibrons  eonneetive-t issue  portions  of  the  tnnn)r  apju-ar  -ilisteninu-  white, 
ihe  nuiseular  portions  more  reddish-white  or  clear  reddish-<;ra\ .  'liie 
Hpindle-shaped  musele-tibres  may  be  isolated  by  teasin<;  a.  bit  of  tlie 
jumoror  by  maeeration  of  the  same  for  twenty-four  hours  inatwenty- 
her-cent  nitric-acid  solution  or  for  twenty  to  thirty  minutes  in  a  thirty- 
'our-per-cent  soluti<m  of  potassium  hydroxide.  Tn  lon,uitudinal  sectioiis 
'he  musele-tibres  are  most  easily  lecounized  by  their  rodsliaptd  inn-lei 
[Figs.  270,  2S0\  as  well  as  by  the  rei;ular  structure  (»f  the  cells  in  bands 
!)r  strands.  In  cross  section  the  muscle-cells  api)ear  as  small  llattened 
ells  containing-  in  their  centres  the  transversely  cut  nuclei  (Fig.  271)). 

The  leiomyomataare  benign  tumors,  but  often  leach  a  very  large  size, 
md  sometimes  undergo  a  sarcomatous  proliferation  and  set  uj)  nu'tastases. 
The  nuiscle-cells  themselves  may  change  their  charactei- and  ])roIit"erate 
)r  the  intermuscular  connective  tissue  may  take  on  a  sarcomal(»ns  ]irt)- 
ifenition.  In  tibromyomata  of  the  utei-ns  there  not  infre(|uently  occnr 
atty  degeneration  and  softening,  which  may  lead  to  the  disintegiat  ion 
if  the  tumor  or  to  the  formation  of  cystic  cavities.  Calcilication  and 
)oue-formation  may  also  occur.  Through  degeneration  and  atrophy  of 
he  muscle-fibres  a  myofibroma  may  become  transforme<l  into  a  fibroma. 
A  rhabdomyoma   (Zenker),  or  myoma  sfriocellulare  {Xhvhow ),  is  on 


'5j^:i:^EiiS2;^i^^^j_^__,--:^^:_^^ 


Fio.281.— Cellsfn>m  a  rhaMnnivnma.  (After  Rihhcrt  and  WoIffnshcrjrtT.l  a.  ?i.  c,  c.  Stri»tf<l  flhn-s 
varying tliickness;  </.  slemler  miclcateil  flbrc  without  striation;  c,  spiiKllc-cell  with  InnKltiKlliiul  .slrrn- 
m; /,  spindle-cells  with  lonjrituiiinal  and  transverse  striation;  (/,  spindkMvlls,  wlihoni  sirintlun,  wllli 
>ngated  processes ;  h,  i,  round  cells  with  concentric  and  radial  striation. 

le  whole  a  rare  tumor.  Its  most  characterist  it;  feat nre  is  the  presence 
f  striated  muscle-libies,  Avhieh  in])aitare  fnll.\  developed  and  in  jiait 
ndeveloped.  When  well  developed  the  mnscle-libres  lorni  miilt  innclear 
indsof  varying  width,  which  ])resent  a  cross-st  rial  ion  (Fig.  2S1,  a,  b, 
I,  and  in  part  also  a  longitudinal  striation  (c,f).  The  nndeveh)j)ed 
>rms  consist  of  narrow  bands  withont  transv<M'se  slriati<nis  (</) ;  of 
)iudle-cells  with  long-drawn-out  thread-like  processes  withont  transverse 


412  TUMORS. 

striation  (<jr)  or  witli  partial  striatiou  (/ )  ;  or,  further,  of  round  cells  of 
different  sizes,  which  jiresent  either  a  radial  or  a  concentric  tibrillation 
or  striation  {Ji,  i).  Besides  these  there  are  also  cells  which  possess  no 
especial  characteristics,  so  that  it  is  impossible  to  decide  whether  they. 
are  young  undeveloped  muscle-cells  or  connective-tissue  cells.  The. 
bands  as  well  as  the  spindles  are  usually  arranged  in  interlacing  bundles. 
It  is  usually  not  possible  to  demonstrate  with  certainty  the  presence  of  ai 
sarcolemma  on  the  surface  of  the  fibres;  but  various  delicate  membranes^ 
ha^e  been  described  by  different  authors,  which  probably  are  to  be  re-, 
garded  as  representing  portions  of  a  sarcolemma. 

Ehabdomyomata  of  the  heart,  in  so  far  as  they  do  not  consist  of  r' 
formation  of  delicate  transversely  striated  muscle -fibres,  are  made  up  oi: 
a  delicate  network  supported  by  connective-tissue  bands,  in  the  eleay 
spaces  of  which  network  there  lie  spider-like  cells,  whose  processes  art; 
partly  free,  and  partly  continuous  with  the  reticulum.  According  ti 
Seiffert,  these  cells  are  to  be  regarded  as  enlarged  embryonal  muscle  i 
cells,  which,  in  the  event  of  an  overi^roduction  of  the  structureless  pro! 
toplasmic  portion,  have  formed  no  transversely  striated  covering,  j 

Ehabdomyomata  occur  in  the  kidney  or  its  pelvis,  in  the  testicle^! 
uterus,  the  vagina,  bladder,  muscles,  heart,  nerves,  subcutaneous  tissue 
mediastinum,  oesophagus,  etc.,  and  form  nodular,  or,  in  case  they  ar; 
situated  on  the  surface  of  a  mucous  membrane,  papillomatous  and  polji 
poid  tumors,  which  vary  greatly  in  size.  They  develop  from  stripe  ^ 
muscle,  possibly  also  from  smooth  muscle  (uterus).  In  the  kidneys  au' 
testicles  they  either  form  circumscribed  nodules,  or  lead  to  a  totj; 
destruction  of  the  organ.  The  origin  of  the  tumor  in  these  cases  is  prol' 
ably  from  misplaced  anlage  of  muscle-tissue;  and  accordingly  suc; 
growths  are  most  frequently  congenital.  They  may,  however,  develc,' 
first  at  an  advanced  age.  Occasionally  they  enclose  other  tissues,  f(| 
example,  cartilage.  Moreover,  muscle-fibres  of  corresponding  stages  < 
development  occur  in  the  complex  tumors  of  the  testicles  and  kidne; 
(see  Teratoma). 

If  a  tumor  contains  only  a  few  cells  which  can  be  definitely  reco 
nized  as  muscle-fibres,  while  the  majority  of  the  cells  have  no  speci:' 
character,  the  tumor  is  ordinarily  designated  a  rhabdomyosarcoma. 

Literature. 

(Leiomyoma  and  Bhabdo7nyoma.) 

Arnold:  Glykogenhaltiges  Myoma  striocellnlare  des  Hodens.     Beitr.  v.  Ziegler,  vi 

1890. 
Becker:  ^Nlnskelgeschwlilste  dfs  Hodens.     A^ircli.  Arch..  163  Bd.,  1901. 
Brodowski:  j\Iyosarkom  des  Magens.     Virch.  Arcli.,  67  Bd.,  1876. 
Cagnetto:  Rnlidomioma  del  ciiore.    Arch,  per  le  Sc.  Med.,  xxvii.,  1903  (Lit.). 
Cesaris-Demel :  Rabdomioma  del  cuore.     Arch,  per  le  Sc.  Med.,  xix.,  1895  (Lit.). 
Cohen:  Ilistogenese  der  jMyonie.     Virch.  Arch.,  loB  Bd.,  1899. 
Cohnheim:  Congenitales  quergestreiftes  Muskelsarkom  der  Niere.     Virch.  Arch.,,» 

Bd.,1875. 
Eberth:  Myoma  sarcomatodes  renum.     Virch.  Arch.,  55  Bd.,  1872. 
Fujinami:  Rhabdomyosarkom  im  Miiskel.     Virch.  Arch.,  160  Bd.,  1900. 
Gebhard:  IMvome  d.  Uterus.     Handb.  v.  Veit,  ii.,  Wiesbaden,  1897  (Lit.). 
Helbing:  Rhabdomyom  an  Stelle  der  1.  Lunge.     Cbl.  f.  allg.  Path.,  ix.,  18! 
Herzog:  Cutaneous  Myoma.     .Tourn.  of  Cntan.  and  Genito-urinery  Dis..  1897  (Lit^ 
Hess:  Ein  Fall  von  midtiplen  Dermatomyomen  an  der  Nase.     Virch.  Arch.,  130^ 

1S9(). 
Huber  u.  Bostrom:  Myosarkom  der  Niere.     Deut.  Arch.  f.  kiln.  Med.,  23  Bd. 
Jadassohn:  Zur  Kenntniss  der  multiplen  Myome  der  Haut.     Virch.  Arch.,  131. -i 

1890. 


fi 


GLIOMA. 


41.S 


iKunze:  Ziir  C'usuistik  der  Myonie  dcs  ]\I;igens.     Arch.  f.  klin.  Chir.,  40  Bd.,  1800. 
L.artigau  ami  Larkin:  ^Multiple  Leiomyomata  of  the  Kidney.     Journ.  of  Med.  Hes., 

IIIOI. 
Lukasiewicz:  ^Multiple  Dormatoinyomc.     Arch.  f.  Derm.,  xxiv.,  1892. 
Vlarc:  Leiomyoma  subcutaneum  congenituin.     Virch.  Areli.,  125  lid.,  1891. 
ttarchand:  Myosarcoma  strioeelluhuc  der  Niere.     Virch.  Arcli..  73  IJd.,  1878;  I'fher 

cine  Gcsc  hwulst  mit  quersjestreifteu  ;Mu.skelfasern.     Tb.,  100  Rd..  18S."). 
Hastny:  .^[aliKIle  .Myome  des  I'tenis.     Z.  f.   lleilk.,  22  lid.,  I!i02. 
«Ieumanii:  Myoma  striocelhilare  des  ITodens.     Virch.  Arch.,  !():{  lid.,  1K86;  ^Multiple 

Dermatomyome.     Arch.  f.  Derm.,  39  lid.,  1897. 
')rlandi:  Kabdomioma  del  uervo  iscliiadico.     Arcli.  ))er  Ic  Sc  :\lcd..  \i\.,  189.")  (Lit.). 
?aviot  et  Berard:   Caucer  luusculaire  lisse  (maligue  Mvomc).     An-li.  de  nu'd.  exp., 

1S97. 
?ernice:  ^Myosarcoma  striocelhilare  dos  Uterus.     Virch.  Arcii.,  li:iHd.,  1888. 
^rudden:  Kliabdomyom  d.  Parotis.     Amer.  Jour,  of  tiie  Med.  .Sciences.  April,  18S3. 
'.  Reckling-hausen:  Die  Adenomyome  u.  Cystadeuome  des  I'tenis,  lierlin,  189G. 
libbert.   ,^lvosarcoma  striocelhilare  des  NieVeiibeckens.     Virch.  Arch.,  lUOIid.;   Zur 

Kenntn.  der  Hhabdoiinomc.     lb.,  130  Bd..  1892. 
licker:  Aetiolo.uie  der  Ut'erusgesclnviilste.     Virch.  Arch.,  142  Bd.,  189.1. 
Jeiffert:  :Multiple  Hhabdomyome  des  Ilerzcns.     Beitr.  v.  Ziegler,  xxvii.,  1900. 
imith:  Fibromyomatous  Tumors  of  the  Vagina.     Amer.  Journ.  of  ()l)st.,  1902. 
Jteiner:  ]\[yome  d.  3Iagendarmkanales.     Beitr.  v.  Bruns,  xxii.,  1898  (Lit.). 
?usini:  Kabdomioangioma  del  dorso.     Arch,  per  le  Sc.  Med.,  xx.,  1896. 
rirchow:  Die  krankhaften  Geschwiilste,  iii.,  186.5. 
Villiams:  Histogenese  d.  Uterussarkonie  (.Myoma  sarcomatodes).     Zeitschr.  f.  lleilk., 

XV..  1894. 
Volfensberger :  Rhabdomyom  der  Speiscrohre.     Beitr.  v.  Ziegler,  xv.,  1894. 
Zenker,  K. :  Khabdomyosarkom  der  Orbita.     Virch.  Arch.,  120  Bd.,  1890. 

(h)    Glioma  and  licuroglioma  Ganglionarc. 

110.   A  glioma  is  a  tumor  which  develops  from  the  crlh  of  ihr  sup- 
wiinff  ti-ssiic  of  the  central  nervous  system  (iieiiro<;lia),  ami  in  its   fully 
develoiK'd   condition    consists    os-scnlially   of 
these  cells.     In  the  brain  tiie  liliomata  form 
tumors,    M'hich    for   the    mo.st    i);irt   are   not 
sharply  defined  from  the  normal  br;iin-sub- 
stance,  but  pass  into  the 
latter    by  insensible  jjji-a- 
"^P^ily'^JriAl       dalions.      At   times   they 


anceof  the  normal  ti.ssne- 
contrasts  between  the  dif- 
feient     elements    of    the 
bi-ain,    j^ive   evidence    to 
the   eye  that  a  tumor  is 
l)resent.      Jn    the    spinal 
cord  tliey  arista  most  fre- 
qui'iitiy  in  the   neighbor- 
hood of  the  central  canal, 
and    nia.\-  extend    ovry    a 
larji'c  port  ion  of  t  lie  ((ud. 
Their    appearance  varies    greatly;    sometimes  they  are  ligiit-gray, 
Dmewhat  translucent,  and  similar  in  coh)r  to  that  of  the  cortex,  and 
loderately  firm  in  consistence;    at  other  times  they  are  more  grayish- 
hite,  denser,  and  firmer;  and  again  they  are  not  infrequtntly  grayi.^h- 


FiG.  282.— Glioma  cerebri.  A,  Cells  isolated  by  teaslnp  and 
ained  with  carmine.  B,  Section  from  same  jrlioina  after  harUen- 
ij? in  Muller's  tluid  (BLsmarck  brown).     X  3.tO. 


414 


TUMORS. 


Fig.  283.— Section  of  a  glioma  of  the  cerebruj 
with  astroevtes  (Jliiller's  fluid,  ^■•^•^"t"-'"'' 
Mallory's  method.)     X  500. 


red  or  dark  red  in  color  and  are  then  sharply  circnmscribed  from  the  su: 
rounding  brain  substance.  In  the  last  case  they  are  traversed  by  numej 
ous  hxrge  vessels.  Gliomata  well  sujiplied  with  blood  often  contai 
hsemorrhagic  areas.  Fatty  degeneration,  softening,  and  destruction  ( 
the  tissue  are  also  of  common  occurrence. 

A  section  of  a  fully  developed  glioma  shows  under  the  microscope 
network  of  extremely  delicate  glistening  fibrillte  (Fig.  282,  B),  in  whic: 
are  imbedded  numerous  short  oval  nuclei.  About  the  miclei  there  [ 
but  a  scanty  amount  of  protoi^lasm,  and  this  can  be  distinguished  onl 
with  difiiculty.  When  examined  in  the  fresh  state  or  after  maceratio 
in  Midler's  fluid  it  may  be  seen  dis- 
tinctly that  these  nuclei  belong  to 
cells  (astrocytes)  which  are  charac- 
terized by  a  great  nimiber  of  fine 
processes  extending  in  all  directions, 
and  often  branching  (Fig.  282,  A). 
By  proper  staining-methods  the  con- 
nection between  some  of  the  fibres 
may  be  demonstrated  also  in  sections 
(Fig.  283). 

The  cells  are  very  similar  to  nor- 
mal glia-cells  (short-processed  or 
long-i^rocessed) ;  but  are  not  in- 
frequently much  larger,  occasion- 
ally more  plump,  and  some  may 
possess  two,  three,  or  four  nuclei. 

The  development  of  gliomata  tal-es  i 

2)Iaee  oydinarili/  from  the  siqyportinf/  eells  of  the  white  and  gray  substauc| 
A  preponderance  of  cells  with  a  slight  development  of  the  cell-processi 
leads  to  the  formation  of  inedullarj/  gliomata;  while  a  more  marked  fc! 
mation  of  processes  and  of  the  tibrillated  ground-substance  gives  rij 
to  hard  forms.  As  the  result  of  the  proliferation  of  the  perivascul! 
connective  tissue  gliosarcomata  may  be  formed. 

In  gliomata  developing  in  the  neighborhood  of  the  ependyma,  t 
ependymal  epithelium,  consisting  of  cylindrical  cells  with  a  basal  proce? 
may  also  share  in  the  proliferation,  so  that  the  surface  of  the  tumor  becoml 
covered  with  a  layer  of  ependymal  cells.  Epithelial  ingrowths  resembli-, 
gland-duets  may  be  formed  so  that  the  tumor  in  part  tal-es  on  the  characr 
of  an  epithelial  adenoma  (neuro-epithelioma  adenomatosum  gliomatosum). 
similar  appearance  may  be  jiroduced  when,  as  the  result  of  disturbanc] 
of  development,  misplaced  portions  of  the  medullary  canal  lie  witbl 
the  glioma. 

Proliferations  arising  from  the  epithelium  of  the  plexus  bear  t  ^ 
character  of  epithelial  growths. 

A  neuroglioma  ganglionare  (Fig.  284)  is  a  tumor  of  the  eent' 
nervous  si/stcm,  composed  of  hyi:)er plastic  glia-tissue,  ganglion-eells,  a' 
nerve-Jibres,  and  foi-ms  either  poorly  defined  swellings  of  larger  portio^ 
of  the  brain,  or  circumscribed,  nodnlar  enlargements  of  smaller  portioij 
To  the  naked  eye  the  structure  of  the  brain  may  in  general  appear  to  ) 
still  preserved,  though  the  difference  between  the  cortical  and  med>|- 
lary  substance  is  less  distinct  than  normal,  and  the  tissue  throughout  ? 
white  or  grayish- white,  or  spotted  gray  and  white,  and  at  the  same  tiii 
more  or  less  hardened. 

The  main  portions  of  these  masses  consist  of  a  more  or  less  thick  gl 


GLIOMA.  415 

issue  containing:  a  certain  number  of  nerve-nhres  («1)  ami  j;an<;lion- 
ells  {a,  b,  c),  or  cells  resemblinji-  <ian<;iion-cells,  no!  only  in  Hit'  eorlicnl 
ssue,  but  also  in  the  whitt'  substance. 

Probably  all  of  these  loiinal ions  are  1k)  be  rcmndrd  :is  tlir  rcsnlt  of 
isturbances  of  the  embryonal  (U'\elo|)nu'nt  of  tiic  inuin-  liiat  is,  ;is  local 
malformations  of  the  biain,  which  aic  characterized  essentially  by  a 
]>(ttlu>l(>;/ir<il  <lrn'l(>j))ii('iit  of  ncunxjiia  ((/lionidfthsi.s)  and  i)y  a  de\  ('lo])ment  of 
(■art  of  the  neuroblasts,  ])robably  also  of  the  si)oniiioblasls,  into  lar.ue 
lUffUon-Uke  cells  («)  such  as  are  not  found  normally  in  the  brain. 


f 


1 

Fig.  2S4.— Section  from  a  nodular  neuroglioma  pranprlionarc  of  the  central  eonvoliitinii  of  tlic  (•••rcliniin 
uller's  fluiii,  Weierert's  stain).  .1,  Portion  of  tissue  rich  in  ganirlion  cells.  B,  Portion  of  tissue  conUiln- 
r  nerve-Hbres.  C,  jelly-like  portion,  o.  Ganelion-cells  arrantreil  in  proups;  /»,  sciitiere<l  panKlion-<-ells; 
ranglion-cells  with  two  nuclei ;  d,  nerve-flbres  with  medullary  sheath  ;  e,  Blian'ells  ;  /,  lilood-vessel.   X  T,'i. 

The  term  glioma  is  also  applied  to  certain  tunu)rs  of  the  retina  occur- 

iigdniini;-  childhood.     These  growths,  a  ceitain  jKntioii  of  wliicli  are 

«j'  congenital  origin,  are  evidently  to  be  referred  to  some  disl  nrbaiice  in 

U'develoitnuMit  of  the  retina.     They  form  cellnlar,  soft,  white  or  reddish 

jniors,  the  gieater  jiart  of  which  consists  of  small,  i-onnd  or  irregidar 

lis  poor  in  protoplasm,  resembling  the  cells  of  the  stratum  granulosum. 

part  they  possess  smaller  or  hiiger  processes.     These  cells  are  found 

•st  preserved  in  the  neighl)Oihood  of  tlie  blood-vessels,  while  in  oilier 

rtions  of  the  tunnn*  they  often  show  retrograde  changes,     'i'lie  liiinor 

ly  also  contain  ganglion-cells,   cylindrical  cells,   and  jx-cnliar  noette 

i»d  ribbon-like  cell-formations  (^Vintersteiller ),   these  latter  being  re- 

Irded  as  aggregations  of  i-ods  and  cones.      Wintersleiner  has.  t  liciefore, 

(signaled  tlie  tumor  ;i  iicttnxjtilhrHoiiKi. 

Tlie  glioma  of  the  i-etina often  shows  area.s  of  necrosis  in  its  <-ciit  lal 
l^rtion.  In  its  growth  it  nniy  l)reak  into  the  retrolndbar  space,  <.r  foi-- 
urd  through  the  cornea  and  sclera;  it  recurs  aft<'r  oi>eratioii,  and  gixcs 
];e  to  metastases. 

With  reference  to  the  orijrin  of  neurou:li;i  and  jiaiifrlion-cclls  fnuii  tlic  (TtiMlcnii, 
^^ious  writers  clas.s  the  different  forms  of  (jlioviotu  with  liic  cpitliclial  tumors. 
1  so  far  a.s  the  ependynial  proliferations  rcscnil)linti  ei)ithelioinala  ami  adi'iioniatu 
(  118.  119)  are  concerned,  such  a  classification  is  justified.  The  ordiii.irv  <rlionialji, 
wever,  show  a  structure  resembling  that  of  the  other  connective-tissue  tumors,  .so 
tit  it  is  more  proper  to  class  them  with  the  latter. 


416  TUMORS.  . 

Literature.  j 

(Glioma  and  Neuroglioma.)  j 

Baumann:  Zur  Kenntniss  der  Gliomeii.  Neurogliome.     Beitr.  v.  Ziegler,  ii.,  1888,' 
500.  I 

Bittorf:    Ilirn-  u.  Ri'ickenmarksgeschwiilste.     Beitr.  v.  Ziegler,  xxxv.,  1904.  '• 

Eisenlohr:  GliomderNetzhaut.     Virch.   Arch.,  123  Bd.,  1891.  { 

Emanuel:   Gliom.  d.  Pars  cil.  retinae.     Virch.  Arch.,  161  Bd.,  1900.  \ 

Ernst:    Missbildung  d.  Kleinhirns.     Beitr.  von  Ziegler,  xvii.,  1895.  ; 

Gayet  c't  Poncet:   Gliome  de  la  retine.     Arch,  de  phys.,  ii.,  1875. 
Gerhardt:   Gliome.     Festschr.  z.  Sacularfeier  der  Universitat,  Wiirzburg,  1882. 
Greeff:    Bau  d.  Glioma  retinae.     Deut.  nied.  Woch.,  1896.  ' 

Lievy:    Zentralkorperchen  in  Gliomen.     Virch.  Arch.,  171  Bd.,  1903.  j 

Linck:  Ependymiire  Gliome.     Beitr.  v.  Ziegler,  xxxiii.,  1903.  j 

Muthmann  u.  Sauerbeck:  Gliageschw.  d.  4.  Ventrikels.    B.  v.  Ziegler,  xxxiv.,  19(. 
Neumann:   Gliom  der  Substantia  perforata.     Virch.  Arch.,  61  Bd.,  1874.  I 

Pusey:  The  Genesis  of  Glioma  Retina?  in  Neuroglia.    Johns  Hopkins  Hosp.  Bull.,  Ii!!. 
Reisinger:   Ueber  das  Gliom  des  Riickenmarks.     Virch.  Arch.,  98  Bd.,  1884.  ; 

Rosenthal:   Neuroepithelioma  gliomatosum.     Beitr.  v.  Ziegler,  xxvii.,  1900.  | 

Saxer:   Gliome.     Beitr.  v.  Ziegler,  xxxii.,  1902.  ! 

Scaffidi:  HistogenesedesNetzhautglioms.     V.  A.,  173  Bd.,  1903.  j 

Simon:  Spinnenzellen  u.  Pinselzellen  im  Gliom.     Virch.  Arch.,  61  Bd.,  1874.  i 

Steinhaus:   Netzhautgliome.     Cbl.  f.  allg.  Path.,  xi.,  1900.  ; 

Stertz:  Multiple  Gliomatose  des  Gehirns.     B.  v.  Ziegler,  xxxvii.,  1905.  • 

Stolpe:   Eigenartiges  Gliom.     Festschr.  d.  Krankenh.,  Dresden,  1899.  ] 

Strobe:   Bau  u.  Entstehung  der  Gliome.     Beitr.  v.  Ziegler,  xix.,  1896.  j 

Thomas  and  Hamilton:   Neuroglioma  of  the  Brain.     Journ.  of  Exp.  Med.,  ii.,  \VJ. 
Virchow:   Die  krankhaften  Geschwtilste,  ii.,  1864. 
Wintersteiner:   Neuroepithelioma  (Glioma)  retinae,  Wien,  1896  (Lit.).  ' 

({)  Amputation  Neuroma,  Neurofibroma,  and  the  True  Neuroma.     \ 

§  111.  The  tumors  designated  neuromata  occur  most  frequeutlyin 
the  ends  of  amputated  nerves,  where  they  form  more  or  less  promirjit 
swellings,  either  circumscribed  or  blending  into  the  surrounding  \\m 
without  any  clearly  defined  demarcation.  From  the  conditions  of  t]|ir 
origin  they  are  known  as  amputation-neuromata  (Fig.  285,  h).  Thede'l- 
opment  of  these  neuromata  is  to  be  referred  to  the  changes  taking  p  ije 
after  the  nerves  have  been  severed ;  during  the  development  of  couueeve 
tissue  in  the  stump  the  ends  of  the  axis-cylinders  of  the  proximal  porjm 
of  the  affected  nerve  divide  and  grow  longitudinally,  so  that  the  sir- 
tissue  comes  to  be  penetrated  by  nerves  which  at  first  have  no  sheajs, 
but  are  soon  surrounded  by  medullary  sheaths.  The  mass  of  nejes 
penetrating  into  the  granulation  tissue  may  be  large,  so  that  the  '|n- 
nective  tissue  after  a  certain  length  of  time  may  contain  a  very  Bh 
supply  of  nerves,  which,  radiating  from  the  end  of  the  old  nerve,  exiad 
into  the  connective  tissue  in  all  directions  (Fig.  285,  &).  The  prcisss 
is,  therefore,  an  example  of  a  useless  regenerative  proliferation  of  a  m^^- 
stump  exceeding  the  physiological  needs.  j 

As  another  form  of  so-called  neuromata  are  classed  those  groihs 
developing  spontaneously,  without  external  cause,  along  the  couKjol 
nerves ;  and  which  consist  essentially  of  an  increase  in  the  connective  tm 
of  the  nerve,  usually  of  the  outer,  more  rarely  of  the  inner  layer  oijhe 
eudoneurium.  j 

At  the  point  of  tumor-growth  the  nerve-bundles  become  surrou  led 
by  a  more  or  less  thick  layer  of  connective  tissue,  which  is  usually  l',se, 
iiiore  rarely  dense  (Fig.  286,  h,  d),  or  the  bundles  may  be  split  ijart 
into  their  individual  fibres  (c).  Occasionally  the  perineurinni  1|ies 
part  in  the  proliferation.  In  the  case  of  large  nerve-trunks  the  ep  pu- 
riiim  may  be  affected  in  association  with  the  eudoneurium  and  perpu 


L 


NE^•H()^iA. 


417 


num  of  the  individual  bundles,  aHlmu^li  tlir  process  is  most  rictint-ntly 
I'oufiued  ta  the  endoneuriuni. 

j  Aooordin.u-  to  tlieir  structure  these  tnniois  ai'e  not  true  neuioimila. 
tMit  are  neurofibromata  01-  fibromata  nervorum.  Tin  v  are  usually 
A'  muUipIc  occurrence,  and  may  extend  throu.-ihout  the  entire  ])eripheral 
lervous  system,  but  are  nu)re  otten  limited  to  a  (U'linite  area  of  nerve- 
ilistribution.  In  very  rare  eases  they  occur  in  the  neixe-roots  and  spimd 
Irord.  The  uodules  aie  sometimes  situated  aloni;-  the  course  of  the 
uerve-trunks,  sometimes  on  llie  liner 
branches,  most  fre(inen(ly  of  tlie  cutane- 
ous uerves;  and  in  the  skin  form  more  or 
less  uumerous,  lar<;«'r  or  smaih-r,  tnnn)r- 
mnlules,  for  the  ji'reater  ]»art  of  soft  eon- 
sistenc«\  to  Avhicli  the  (h-si^iiat ion  multi- 
ple fibromata  of  the  skin  is  usually 
applied.  Tlu'  smaHe.«>t  n(»(hiU's  can  be 
seen  only  with  the  microscope;  tlie  ma- 
jority vary  in  size  from  that  of  a  ])ea  to 
that  of  a  hazel-nut.  Individual  tumors 
may  reaeh  the  size  of  a  man's  list,  the 
nerve-fibres  beinj^  Avholly  lost  sijiht  of  in 
the  j;reat  mass  of  eonneetive  tissue.  At- 
rophy of  the  fibi-es  may  he  caused  l)y  th«^ 
increasing-  coiiiieeti\e  tissue,  the  liltres 
linally  vanishing;  completely.  In  addi- 
tion to  the  formation  of  circumscribed 
nodules  there  nuiy  occur  also  in  the  af- 
fected area  a  (lijf'ti.sr  ihichni'mfi  of  the  nerves 
from  hijpeiirophii  of  their  eoiuieetire  tiftftue. 
Moreover,  with  this  condition  thei-e  may 
l)e  associated  a  hyi)ertrophio  ]»ronfera- 
tion  of  the  conuectixe  tissue  of  the  skin 
iiid  subcutaneous  tissue,  leadinu'  to  rh- 
l)li(nifi(isis-/ike  thickeniiif/s  of  the  .s/./». 

A  third  foini  of  false  neuioma  is  tiie 
cirsoid  neuroma  (liruns)  or  plexiform 
neuroma  (Veiiieuil),  a  tunmr  formation 
wiiicli  is  characterized  by  tlie  develop- 
nu'ut  in  the  domain  of  one  or  moi-e  ner\-e- 
branches  of  ;i  com ohition  of  tendril-like, 
twisted  or  inter\vo\<'n,  thickened  and 
nodular  nerve-sti-auds  (Fij;.  L'ST  ).  \\'\wn 
examined  in  detail  this  formation  is  also 
found  to  depend  essentially  upon  a  filtro- 
matoHiH  of  the  verres  (F\}i.  2Sf>),  the  jjpo- 
'eration  of  the  endoneurium  resultiu^^  ])artly  in  a  diffuse  and  i)artly 
a  nodular  thickeninj;-  of  the  nerves.  In  addition,  it  may  be  found 
i  such  formations  that  the  nerves  of  the  affected  aiea  are  Iruiflhrunt 
fd  therehi/  rnulrretl  tortuous,  while  at  the  sann-  tinu'  the  iirrns  <irr  ///- 
i?ased  ill  nKin/jer,  m  that  the  numix-r  of  the  nerves  of  the  skin  and 
tbcutaneous  tissues  is  o-reater  than  under  normal  conditions.  The  con- 
<:ion  mu.st,  therefore,  be  rejjarded  as  one  of  tru(^  neuroma,  a  ii«  uromo 
t*wm.  as.sociated  with  ii  fibromatosis.  The  nerves  ar«^  for  the  <rreat«'r  part 
imullated  {neuroma  m'yellnlcum).     It  is  very  dillicult  to  determine  to 


10.  285.  — Aniimtation-iifuroma  (if  Hii- 
I  itlc  nerv-e  (nine  years  after  ainiuitati(  m 
'thenene).  I><>ngitudinal  section,  fi, 
4ne;     h.    neuroma.      Drawn    from    a 

■paratlon  which  had  been  hardened  in 

ller's  nuid.    x  3. 


418 


TUMORS. 


what  extent  nou-mednllated  ller^'es  are  present  in  snch  formations,  U 
nevertheless  cases  have  been  reported  in  which  the  nerve-fibres  were  ^r 
the  greater  part  nou-mednllated  (neuroma  amyelinicum).     Cirsoid  n«- 


X  y 


6^ 


Tig.  2S6.— Nerves  from  an  elephantiasis-like  cirsoid  neuroma  of  the  cheek  and  lower  jaw  (FlemnrW 
solution,  safranin).  o,  h,  Nerves,  the  outer  layers  of  whose  endoneuriiim  have  undergone  markeiro- 
liferation ;  the  nerve-fibres  lie  in  the  axial  portion  ;  c,  nerve  with  markedly  proliferated  endoneuriun  jufl 
separated  nerve-fibres ;  d,  thickened  nerve  with  a  small  strand  of  nerve-flbres  at  the  left  end ;  c,  loos^pn- 
nective  tissue,  rich  in  nuclei  and  containing  fat,  lying  between  the  nerves.    X7.  I 


romata  occur  on  the  head, 
trunk,  and  extremities,  and 
give  rise  usually  to  elephanti- 
asis-like disfigurations  of  the 
affected  areas. 

True  neuromata  consist- 
ing of  nerve-fibres  and  ganglion- 
cells  (neuroma  ganglioceliulare 
verum)  are  rare  tumors;  but 
from  the  observations  of 
Weichselbaum,  Beueke, 
Busse,  Kuauss,  Schmidt  and 
others,  the  occurrence  of  such 
growths  cannot  be  doubted. 
They  form  tumors  varying  in 
size  from  that  of  a  millet-seed 
to  that  of  an  apple,  and  de- 
velop particularly  in  the  sym- 
pathetic system.  In  a  case 
described  by  Knauss  there 
were  present  multiple,  nod- 
ular neuromata  of  the  skin 
containing  nerve-cells,  and  it 
is  probable  that  these  growths 
had  their  origin  in  sympa- 
thetic nerves  containing  gan- 


rifx  >7  (  iiM  1 1  iKutonn  of  tin  sicnlitprion  ^^' 
a  d(  iwiiiir  b\  1'  Bniiis)  Ihf  nxUiIir  twi-itd  and^r- 
wo\eii  ner\es  ait  in  pait  fiee  ((/i  and  in  put  (h)  >  erea 
b>  L-wunective  tissue.      I«atural  siZc. 


NKIKOMA     .\\n     NKIKOI  IHKOM  \.  ll'.t 

:lion-('clls.  Theso  tumors  consist  of  coimrcfiv*' t issiir.  noii-jiu'dullalcd 
.11(1  iiKHluUattMl  norve-libies,  and  iiaiinlioii-cclls  wliidi  rcsfuihlc  lliosf  of 
he  synipatlietit' jian^lia. 

Both  Ww  uritrofihnniKi  and  the  line  lu  iinnmi  arc,  as  rt'uards  1  licii- (uiuiii, 
ohe  Yi^ii^YVi'd  \o  \\  <-<))i;i<Hit(il  (Dilaijr.  'I'licy  Iniiii  iin  niclaslasrs,  lint  <a>><-> 
(rur  in  whirh  neurofibioniata  lake  on  a  sairoiiiattiiis  <  liaraclrr  and 
heit'by  bccoinc  luali^iiant. 

Literature. 

(Xriiroma  diid  XriirolihroiiKi.) 

.schoff:  Goschwiilste.     Ergebn.  d.  ullsj;.  Patli.,  v.,  UXIO. 

eneke:  Gujigliost' Neuronic.     Cbl.  f.  allg.  Path.,  ix.,  1S9S  ii.  B.  v.  '/..,  xw.,  I'jol. 

orst:  Xeiiroma  ganglionaro.     Sitzber.  tl.  j)hys.-iiu'(l.  Gcs.,  ^\■i■^rzbu^g,  ISUT. 

runs.   P.:  Ucber  das  Kaiikenneuroni.     \iirli.   Arcli.,  oO  15d.,    1^70;' Jieitr.   /..    kliii. 

fliir..  viii.,  1891:  Arcli.  f.  kliu.  Cliir.,  4'3  Bd..  1S92. 
.  Biingner:  ^lultiple  Neurotibronie.     Langenl)wk's  Arcli.,  5.")  Bd.,  1S97. 
usse:  Xeuroiiia  gaugliocellulare  d.  Sympathicus.     Virch.  Arch.,    l."il   Bd.,   Suppl., 

1S!)S. 
Durvoisier:  Die  Xcurome,  Basel,  1886. 

sniarch  u.  Kulenkamp:  Die  elepliantiastischen  Formeii,  Ilftiiiburg,  1SS5. 
:\bris:  (Taiigliciu-uioiiii  del  sist.  sinipat.     A.  per  le  Sc.  nied.,  -xxvii.,  1908. 
lockner:  Neuroma  veruni  gangliosuni.     A.  f.  Gyn.,  63  Bd.,  1901. 
oldman:  Ueitr.  z.  Lelire  von  deu  Neuromcn.     Beifr.  v.  Bruiis,  .x..  1800. 
aenel:  Xciiroganglionia  myelinicum.     Areii.  f.  Psych,,  IM  Bd.,  isjis. 
erczel:  I'eber  Fibrome  u.  Sarkome  der  peripherenXCrvcii.     IJeitr.   v.  Zici^dcr,  viii., 
i     1  silo. 

|)rdan:  Elepliantiasis  congenita.     Beitr.  v.  Zieglcr,  viii.,  1S!»(). 
inauss:  Eciile  multiple  Neurome.     Virch.  Arcli.,  153  Bd.,  lS!is. 
rause:  I'eber  maligne  X^eurome,  1887. 
jcroix  et  Bonnaud:  Xevrome  ple.xifornie  amyelinique.     Arch,   de  med.  exp.,  ii., 

isso. 
tren:  Multiide  allgem.  Neurome.     Nordiskt  IMed.  Ark.,  1897. 
eble  and  Hektoen:  ]Multiple  Fibromata  of  the  Nerves,  etc.     Trs.  Ass.  .if  Anier. 

Phys.,  liiud  (Lit.). 
Recklinghausen:  I'elier  die  multipleii  Filuome  der  Iliuit.     lierliu,  ISS'2. 
Ihmidt:  Gauglieuzelleuhalt.   wahres  Neurom  d.   .Sympathicus.      Virch.    .\nli.    l.").") 

Hd.,  1S99. 
ienon:  Etude  sur  la  structure  du  nevrome,  Bruxelles,  1883. 
I  rube:  Coinitinat.  v.  Neurofibrom  mit  Gliom.  d.  Riickenmarks.     Vinh.  An  h..  1.11 

i!d.,  Supj)!.,  1898. 
'lomson:  On  X'eiiroraa  and  Neurofibromatosis,  Edinburgh,  1900. 
■  rneuil  et  Depaul:  Bull,  de  la  soc.  anat.,  Paris,  1857. 
rchow:  Die  kraiikh.   Geschwulste,  iii. ;  Das  walire  Neurom.     Virch  .Vnh.,  i:'.  Bd., 

is.-,s. 
estphalen.  yiultiple  Fibrome  der  ITaut.  u.  der  X'^erven  mil    I'ebergang  in  .Sarkom, 

imd  .M.-tastasenbildung.     Virch.  Arch.,  1 10  Bil.,  1SM7. 
'' Bichselbaum :  (Jangliiises  Xeurom  der  Xebenniere.     Virch.  .\rc]i.,  s,".  Hd  .  issi. 

(/.)   HarroiiKi. 

>;11-.    -V   sarcoma   in  a   connect i re -fi.ssnr   tumor  trlxisr  r/niiriils,   ril/nr 
if(inm'  of  ilirir  uiiiiiiM'r  or  often   heeaiisr  of  llicir  s'r.r,  prrdoiiiliinlr  on  r  (iir 
■Itiilar  .siih.sl<iitee.      Saiconiata  ar4  clttsfiy  rclah-d  lollic  nndc\  rlu|M-d 
iin>f'tiv«'  ti.ssiics,  .so  that  s:ii<'oiMatons  1  i.ssnc  may  be  comiiart'd  with    im ■ 
lyontit  tis.wr. 
Sarcom;ita  (h-vclop  either  in   ]»i('\  ioiisly  nnrin:d   lissnc   lMdun-in;r  lo 
coniH'ctive-tissne  fiioiij) — as,  for  cxamph-,  in  tlicskin.  sidtciilancoiis 
tjsiU',  int«Mnni.scuhir  connef'tive  tissue,  jieriosleiim,  spinal  e<»rd.  menin 
,  ftonmH'tive  li.ssue  of  tlie  j^hinds,  etc.— (tr  in  some   jnet-xistin;,' <-un 
tive-tissue    tunioi',    as  a  libroma,    myoma,   chondioma.    hy|»eitittphic 


420  TUMORS. 


1 


lympliaugioma,  etc.  The  transformatiou  of  the  parent  tissue  into  tunr 
tissue  takes  place  through  the  growth  aud  multiplication  of  the  exist  g 
cells.  The  division  of  the  cells  takes  place  chiefly  by  mitosis,  aud  mite  ?s 
are  the  more  abundant  the  more  rapid  the  growth  of  the  tumor,  n 
addition  to  typical  mitoses  there  are  frequently  observed  atypical  for  s, 
also  nuclear  fragmentation,  and  more  rarely  segmentation. 

In  their  fully  developed  state  sarcomata  form  more  or  less  shai;.y 
circumscribed  growths.  They  may  appear  in  any  portion  of  the  bly 
where  connective  tissue  is  present ;  but  are  found  in  certain  tissues  n  re 
frequently  than  in  others.  Thus,  for  example,  they  are  found  iir'h 
oftener  in  the  skin,  fascia,  intermuscular  connective  tissue,  bone-ir- 
row,  periosteum,  brain,  and  ovaries,  than  in  the  liver,  intestines,  id 
lungs. 

The  development  aud  form  of  the  cells  vary  greatly  in  diffeiit 
sarcomata.  The  intercellular  substance  is  sometimes  very  scanty,  st, 
and  delicate ;  at  other  times  more  abundant  and  in  character  resemb  iig 
the  ground-substance  of  the  mature  normal  connective-tissue  substau  s. 

The  amount  of  the  intercellular  substance  has  a  marked  iuflmce 
upon  the  consistence  and  color  of  the  tumor.  The  medullary  formsre 
soft  and  very  cellular,  and  poor  in  intercellular  substance;  on  seou 
they  present  a  marrow-like  white  or  grayish-white  surface.  The  hid, 
dense  forms,  on  the  other  hand,  are  poor  in  cells  and  rich  in  fibrous  ir'ir- 
cellular  substance;  they  pass  by  insensible  gradations  into  fibromia. 
Transition-forms  are  known  as  fibrosarcomata.  The  cut  surface  <  a 
sarcoma  presents  a  nearly  uniform  appearance,  in  case  retrograde  cha;ej^ 
or  differences  in  the  blood-content  do  not  cause  alterations  of  the  sa  e: 
it  is  usually  uniformly  smooth,  in  the  medullary  forms  milk-whit«;iL 
the  firmer  varieties  clear  grayish -white,  somewhat  translucent,  or  iw 
of  a  clear  grayish-red  or  grayish-brown  color.  The  hard  forms  are  jis- 
teniug  white  or  yellowish-white. 

The  development  of  the  blood-vessels  varies  greatly ;  sometime.^  In 
vessels  are  very  numerous,  large,  and  ectatic  (teleangiectatic  san-ot:. 
Usually  the  vessels  have  walls  easily  distinguishable  from  the  tumoi  i^ 
sue;  but  the  tumor-cells  may  also  constitute  the  outer  cells  of  the  veel 
wall ;  and  in  such  a  case  the  cells  of  the  vessel-walls  also  take  paj  iu 
the  growth  of  the  tiunor.  ' 

Eetrograde  changes — such  as  fatty  degeneration,  mucous  dege^  ra- 
tion, liquefaction,  caseation,  necrosis,  htemorrhage,  gangrene,  ulcera  m 
etc. — ai-e  of  frequent  occurrence  in  sarcomata. 

The  sarcomatous  tumors  may  be  divided  into  three  classes.  The  i>-i 
of  these  includes  the  simjyie  sarcomata,  or  sarcomata  iu  the  narrower  ns 
— that  is,  tumors  of  the  type  of  embryonal  connective  tissue,  shoAv  g  ;i 
more  or  less  uniform  distribution  of  the  cells  without  the  formatii  oi 
distinct  groups  of  cells.  The  second  class  includes  those  sarcoat;i 
which  show  a  special  arrangement  and  grouping  of  the  individual  elemen  f-" 
that  tumor-formations  arise  which  are  very  similar  to  the  epitJli:*' 
tumors.  The  third  class  is  characterized  by  the  appearance  of  seco  •«' ' 
changes  in  the  cells,  in  the  intercellular  substance,  and  in  the  blood-vessels,  ;iei^ 
changes  giving  to  the  tumors  concerned  a  characteristic  appearance 

The  etiology  of  sarcoma  is  not  a  simple  one.  It  occurs  more  freqiutily 
in  youth  than  iu  old  age.  Some  sarcomata  develop  even  iu  embr  )Dii 
life,  and  the  origin  of  such  may  be  referred  to  some  local  malf orm;  on- 
Occasionally  trauma  appears  to  be  an  exciting  cause.  A  parasitic  ( igi'- 
has  not  been  demonstrated  (see  Etiology  of  Carcinoma).  Usualh»ul} 
one  primary  tumor  is  formed,  but  multiple  primary  sarcomata  some  m('>  \ 


SARCOMA. 


421 


)tt< 


IS 


j)ccnr,  particularly  in  the  skin  and  hdnc-niarrow.  Tl 
rive  rise  to  metastases. 
I  §  li;>.  Tiie  simple  sarcomata  incliidc  holli  soft  mrdnllary  fninis 
.nd  those  of  a  tinner  consistence,  \\iiicli  ])a-ss  by  insensible  decrees  <»f 
iransition  into  the ///>/(>.sYfrfY>/;(r(/(/ and  //7>/yu//(f/ff.  Accord iiiii'  to  tiie  chai-- 
cter  of  the  cells,  st'veral  forms  may  be  distin<iuisl»ed. 
I  The  small  round=celled  sarcomata  ai-e  very  soft.  <|niekly  <;ro\viiij,' 
;nmoi"s,  Avhich  develop  particularly  in  the  connective  tissue  of  Die  nu)tor 
ipparatns  and  supixntini;  framework,  and  also  in  the  skin,  testicles, 
ivaries,  and  lymph  glands.  On  section  they  ai)pear  milky-white,  and 
jccasionally  present  caseous  or  softened  areas.  WIumi  scraped  the  cut 
lurface  yields  a  milky  tlnid.  Their  sti'uctui-e  is  A-ery  simjiU';  the  tumors 
onsist  almost  wholly  of  round  cells  and  blood-\ cssels  ( Fij;-.  2SS,  c). 
I'he  cells  are  small  and  frail;  they  possess  very  little  protoplasm,  and 
ave  spherical  or  slightly  oval,  rather  large,  bhidder-shapetl  iniclei  ( c), 
•hich  ai>pear  to  be  more  highlv  developed  than  the  nuclei  of  lvmj)hoi(i 
pUs. 

Between  the  cells  lies  a  very  scanty  amount  of  lil)i-ogianular  intercel- 

ilar  substance.     The  vessels  traverse  the  masses  of  cells  in  the  form  of 

lin-walled  canals.     If  such  a  tumor  growing  in  muscle  be  examined  at 

s  periphery  it  appears  as  an  aggregation  of  round  cells  (  Fig.  2S.S,  />,  c) 

the  intermuscular   connective   tissue.      Xot   infrequently    lymphoid 

Us  lie  near  the  tumor-cells,  the  nuclei  of  the  former  (//)  staining  more 

iteusely  than  those  of  the  tumor-cells. 

A  second  form  of  round-cell  sarcoma  is  designated  lymphosarcoma 

sarcoma  lymphadenoides  ;    it  imitates  to  a  certain  extent  the  struc- 


/^^   \^ 


Fkj.  288. 


Fi(i.  :.'X!t 


Fig.  288.— Section  through  the  edge  of  a  sarcoma  of  the  hiteriiiiisculiir  coriiiiH-tivr  Ilssiic  of  the  cervical 
iicles  (alcohol,  carmine),  a.  Transverse  section  of  normal  muscle:  k,,  transverse  .s«'cilon  of  an  atrophic 
scle-flhre;  h,  round  cells  of  the  sarcoma,  between  the  niuscle-flbn's;  r,  fully  developed  tumor;  iL, 
■  phocytes.     X  .TOO. 

Fir.  289.— Section  from  a  lymphosarcoma  of  the  nasal  mucous  memhrane  (alcohol,  carmine),    n.  Retlc- 
"  h,  cells  of  the  reticulum;  c,  round  cells;  a  (at  the  upper  left),  bl<M»d-ve»sel  with  prollferutlnfc 
X  .30;). 


of  a  lymph-gland  in  that  the  stroma   for  the  gre:iter  i.ail    of  tlie 

nd  cells  consists  of  a  vascular  ret  iciilnm  (Fig.  l'.S!>,  a),  which  in  jiart 

least  is  composed  of  branching  and  anastomosing  ctdls  (A),  as  may  be 

monstrated  by  shaking  a  small  section  of  the  tumor  in  a  test-lulH'. 

According   to   the   amount   of   reticulum    which    they    i)osses.s,   the 

ilnphosarcomata  may  be  divided  into  the  noj't  and  h<n<l  forms.    In  the  denser 


422  TUMORS. 


1 


varieties  the  reticular  framework  may  take  ou  more  and  more  the  app*'! 
a  nee  of  ordinary  fibrous  connective  tissue.    Especial  forms  of  rouud-ce  id 
sarcoma  arising  in  the  bone-marrow  are  known  as  myelomata. 

Lymphosarcomata  arise  most  frequently  in  the  lymph-glands  andie 
adenoid  tissue  of  the  mucous  membranes,  in  the  spleen  and  meds 


Fig.  290.— Section  from  a  fungoid  large  round-celled  sarcoma  of  the  skin  of  the  leg  (carmine  prenan  U). 

;<  400.  ' 

Fig.  291.— Section  from  a  sarcoma  of  the  mamma  with  cells  of  different  shapes  (alcohol,  Bisrixik- 
brown).  a.  Connective  tissue  ;  h,  sarcoma  tissue  ;  c,  small  cells;  d,  cells  with  hypertrophic  nuclei;  eiiul- 
tlnuclear  cells.    X  300.  : 

1 

tinum,  but  are  found  also  in  other  places.  The  tumor-proliferatioi In- 
volves successively  a  more  or  less  considerable  portion  of  the  lyrih- 
adenoid  tissues  named.  j 

Large  round=celled  sarcomata,  the  cells  of  which  are  much  lato' 
than  those  of  the  forms  just  described,  appear  in  the  same  places  iiido 
the  small  round-celled  variety,  and  closely  resemble  the  latter.  The  Ills 
possess  an  abundant  protoplasm  and  large,  bladder-like,  oval  nuclei  (ig. 
290).  Many  of  the  cells  have  two  nuclei,  some  more  than  two.  Bet^teu 
the  round  cells  there  lies  a  reticulated  intercellular  substance  (Fig.  i!)), 
as  well  as  spindle-shaped  and  branched  cells,  which  together  forijaii 
alveolar  network  in  whose  meshes  lie  the  large  round  epithelial-like  els. 

In  other  forms  of  large  ronnd-celled  sarcomata  the  tumor-cell  ,*re 
very  unequal  in  size  (Fig.  291),  and  at  the  same  time  there  are  mil  Jed 
witii  the  round  cells  elongated  or  irregularly  shaped  cells,  so  thaliiho 
tumor  may  be  called  also  a  sarcoma  with  polymorphous  cells,  'be 
nuclei  likewise  vary  greatly  in  size  (Fig.  291),  and  in  individual  cell  (e) 
may  be  present  in  large  numbers  (multinuclear  giant-cells). 

The  large  round-celled  sarcomata  and  the  polymorphous-celled  Wi- 
ety  are  on  the  whole  less  malignant  than  the  small-celled,  but  thejilBo 
give  rise  to  metastases.  i 

Spindle=celled  sarcomata  belong  to  the  most  commonly  occu  in? 
Iiunors.  As  a  rule,  they  are  much  firmer  than  the  round-celled  f(:ns, 
l)ut  soft  medullary  forms  also  occur.  On  section  they  present  ordir^l.v 
a  grayish-white  or  yellowish-white,  rather  translucent  surface,  ^  if'' 
may  be  more  or  less  reddened  according  to  its  vascularity.  Medi  ai v 
tumors  whose  cells  have  undergone  fatty  degeneration  may  posss  :i 
pure  white  color.  In  general,  these  sarcomata  are  more  benign  tha  the 
round-celled  varieties,  but  their  character  in  this  respect  varies  aortl- 
ing  to  their  location  and  their  richness  in  cells. 


SAHCOMA. 


■\'2:\ 


Accorilin.u-  to  tin' size  of  tlic  «'clls  llicic  iii;i\  Itc  (list  iii^iiislinl  lar^e 
spindled-celied  and  small  spindle-celled  sarcomata.  riir»)ii.!^li  the  teas 
iu«r  «)f  small  ])U'iH'S  (if  the  liiiiior  llic  cflls  ma.\  in  part  he  isdiatcd,  and  in 
[this  way  very  loni;-  spindles  may  bo  obtained  (  l''i.ii.  2!»L' ).  'I'lie  cells  lie 
isiilo  by  side  with  their  Hat  sides  ai)i)roximated,  and  are  jir(tuped  in  bun 
idles,  which,  in  sections,  are  cut  partly  lonjiiludinally,  partly  tiansNcrsely, 
jand  partly  obli(iuely — evidence  that  they  aic  interwoNcn  in  dilVeicnt 
[directions. 

j  The  arraniicmenl  of  the  spindles  in  bnndles  is  often  \ cry  st  rikinu  : 
liu  other  cases  it  is  wantiiii;';  and  the  spindles  lor  considerable  distances 
|ruii  in  the  same  direction.  Sometimes  the  direction  of  the  sjiindles  is 
jdeterniined  by  the  direction  of  the  blood-\  essels — that  is.  the  indix  idnal 
buiullcs  form  sheaths  about  their  ivspectixe  blood-vessels. 
(  Between  the  si)indles  there  is  often  but  a  vei-y  scanty  intercellnlar- 
|snbstance,  or  it  may  not  be  possible  to  demonstrate  in  sections  the  i)res- 
nce  of  such.  In  other  cases  it  maybe  more  abundant,  and  show  a.  libril- 
lar  character.  The  cells  in  such  cases  have  less  ))rotoi»lasm,  so  that  oft<'n 
it  is  scarcely  possible  to  demonstrate  any  protoplasm  around  the  nucleus, 
and  the  processes  at  the  poles  of  the  cells  seem  to  spiin^-  directly  fr(»m 
the  nucleus  (nuclear  libres ).     Huch  varieties  are  dense  and  hard.     They 

represent   tlu>    connect in;;link    i»e- 

tweeu    sjircomata    and    tibr(»maia, 

and  are  desiiiiiated  fibrosarcomata. 

Sarcomata  with  polymorphous 


/■ 


FIG.  292. 
Fig.  292.— Spindle-<-ells  from  a  large  spincDe-^'clled  sjircoina 
Fig.  29.3.  -Cells  from  a  iiiyolof.renous  giant-i-elled  sarciniia  i 


n«i.  2!i:i. 
iif  the  cheek  (leas.il  |)re|)!initli>n>.     X  WO. 
f  III.- tit.la.     (MiiMiiutoxvllii.i      ■    tim. 


|:ells  are  found  also  amon^'  the  spindle-celled   forms;  and  contaii 
iUe-shaped,  pyramidal,  prismatic,  stellate,  and  very  irre;;ular  cell 


md  contain  spin- 
fiuins 


:Fi-.  20.3). 

Both   in  polvmorphoiis-  and   spindle  celled   sarcomata   there   may  be 

iiieroiis -iant  cells  i  l-"i-s.  L'!»l  .•_".».!,  andl'it  I  ;,  so  that 

may  be  applied   to   these  lumoi-s. 


round  more  or  less  ii ., 

[ihe  desijrnation  giant°celled  sarcoma  m.i,  .„..,,, 

'"  ■('  liones,  but  they  may  occur  also  in  of  her 


jl'hey  arise  ]»articnlari>  iiom 

places. 

I     If  a  sarcfmia  develops  in    i)re("-\ist  inj;-    new    growths   llwre    may    be 


424 


TUMORS. 


formed  mixed  tumors,  which  are  known  as   myxosarcoma   (Fig. 
chondrosarcoma  (Fi^.  257),  myosarcoma,  etc. 


Fig.  294. —Giant-celled  sarcoma  of  the  upper  jaw  (Miiller's  fluid,  haniiatoxylin). 


100. 


The  li/n/pJinsarcoma  of  the  h/mpJi-r/htnds  and  li/mphadeuoid  apparatus  of  the  spni 
and  the  mucnis  memhrane  of  the'ffafitroiiifcstinal  tract  gives  rise  to  a  peculiar  diseas  jf 
these  organs,  wliich  is  characterized  by  a  progressive  increase  of  the  lyniphade  id 
tissue,  leading  to  the  fornuitiou  of  extensive  nodules.  Under  these  circumstance!-  le 
characteristic  structure  of  the  lymphadenoid  apparatus  is  lost,  and  the  newiy-for^jd 
tissue  shows  a  marked  departure  from  the  structure  of  typical  lymphadenoid  tissi.— 
namely,  a  tibrous  thickening  of  the  reticulum  or  tlie  formation  of  giant-cells.  Spe 
similar  growths  occur  also  in  other  organs,  such  as  the  liver,  the  disease  caunoije 
looked  upon  as  a  pure  hypertrophy  ot  lymphadenoid  tissue,  but  as  a  tumor-formajm 
Avith  the  production  of  lymphoid  cells.  It  is  also  possible  that  it  is  an  infectious  (iB- 
ease.  Likewise  the  condition  known  as  sarcomatosis  cutis,  which  is  characterized  bjjie 
formation  of  numerous  round-celled  nodules  in  the  skin,  is  to  be  classed  with  it.  _ 

The  myelomata  of  the  bones,  occurring  as  multiple  nodules  either  concealed  in  'le 
bones  or  projecting  from  their  surface,  demand  especial  consideration.  Accordin.'to 
recent  investigations  {Sternheni,  Rihbert,  Hoffmann)  they  are  composed  of  cells  C(?e- 
sponding  either  to  the  myelocytes,  lyn.j'luKytes,  erythroblasts,  or  plasma-cells.       * 

Tlu' common  characteristic  of  the ///////'//".s.//vv,,/,,/ and  innilnma.  is  that,  aside  I'm 
the  reticular  framcAvork,  they  consistcssenlialiy  of  dau'ratins  ,ffree  mesenchymal  di, 
and  are  thereby  differentiated  from  the  ordinary  sarcomata  that  arise  through  the  |o- 
liferation  of  fixed  tissue-cells.  They  form,  therefore,  an  especial  group  among  oe 
connective-tissue  tumors,  but  the  investigations  so  far  carried  out  are  not  sufficieU|tO 
fix  their  position  more  definitely.  j 

Literature.  I 


(Sa)r'0)no.) 


Vortr. ,  Nos.  233,  4, 


Ackerman:  Histogenese  u.  Histologic  d.  Sarkome.     Sanni 

Leipzig,  1883.  _   ' 

Beneke:  Versprengung   v.    Nebennierenkeimen   uebst  Bemerkungen,    etc.     Beitiy. 

Ziegler,  ix.,   1891.  . 

Birch-Hirsohfeld:  Sarkom.     Eulenburg's  Realencyklop.,  xxi.,  1899. 
Bizzozero:  Stroma  di  sarcomi.     Arch,  per  le  Sc.  MeVl.,  ii.,  1878.  i 

Borrmann:  iSarkom.     Ergebn.  d.  a.  Path.,  vii.,  Wiesbaden,  1902  (Lit.). 
Daniels:  Das  Stroma  d.  Sarkome.     Virch.  Arch.,  165  Bd.,  1901.  j 

Dreschfeld:  Bcitrag  zur  Lehre  vom  Lyraphosarkom.     Deut.  med.  AVoch.,   1891.  [ 
Flexner:  Multiple  Lymphosarcomata.     Johns  Hopkins  Hosp.  Kep.,  iii.,  1893._       ■ 
Goldmann:  Verbreitungswege  bosartiger  Geschwiilste.     Bcitr.  v.  Bruns,  xviii.,  Ij7. 
Goppert:  T^ympiiosarkomatose.     Virch.  Arch.,  14-1  Bd.,  Suppl.,  1896  (Lit.), 
van  Heukeiom:  Sarcome  et  inflanuuation.     Bee.  de  trav.   du  Lab.    Boerhaave,  19. 
Hoffmann:  Leber  das  Myelom.     Beitr.  v.  Ziegler,  xxx v.,  1904. 


i 


()H(;a\()II)   sahcoma.  425 

Joseph:  Hjiiilsarkomatosi".     Arrli.  f.  Derm  .  4ti  iJil.,  ISilS. 

V.  Kahlden:  Das  Sarkom  di's  ruTiis.     IJiitr.  v.  Zicglcr.  xiv.,  1S93, 

V.  Kftiwowski:   I'tlx  r  C'allustumorcii.      Iiiaiiir.  Hiss..  Frfil)iirir,  IM)."). 

Langhans:   Das  iiialiiriu"  I.yinpliosaikoiii.      Vinli.  Arch.,  -19  lid..  IST'J. 

Lartigau:   Piiiiiaiy  Sartoiiia  ol' Tliyroid.     Aiiu-r.  .Imirn.  of  >I(»I.  Sr,,  lltOl  (I, it.). 

Linser:  Sarkoiu  dtr  llaiit  init  8(  liriimpfiin.ir.     Hcitr.  v.  Hiiiiis,  '2i\  IM.,  I'.Hld. 

Lbwenthal:  Trauiiiat.    Entsteiuuig   d.  Gi-sclnvnlsii-.     Laiigciilifck's  Anii..    I'.t    15.1.. 

Manz.  Hii'si"ii/.ollt"us;irkom  (1.  Brustdrllst".     Bcitr.  v.  IJrmis.  \iii.,  1S«.)."». 

Neumann:  Saikome  luit  I'udothclialcn  Zellcii.     Arcli.  d.  llcilk.,  xiii.,  isii'j. 

Paltauf:   Lympliosjukom.     EriCfl>M.  d.  allg.  Patli.,  iii..  IsiiT. 

Pawlowski:  Parasitaiu  EiuschUisst-  in  sjukoiiiatriscm  (Jcwchi'.     Vinli.  An  h.,  i:!:?  Hd.. 

is!i:{. 
Perl:  Sark<Mn  der  Vena  cava  inferior.     Vircli.  Anli..  ."i:!  IJd..  isTi. 
Putiata-Kerschbaumer :  Das  Sarkoni  des  Auges.  \Viesl)aden.  I'JOO. 
Ribbert:  Das  Mveloni.     Cbl.  f.  a.  Path.,  xv.,  1904. 

Sanger:  Saiconia  uteri  deeiduo-celiidare.     Areii.  f.  Gyn..  64  Bd.,  lS9:{(Lit.). 
Jehmidt:  ICher  das  Angiostirkoni  der  Mamma.     I.angenltecks  Arch.,   .wxvi.,    ISSS. 
sokolow:  rel)er  die  Entwickeliing  des  Sarkoms  in  den  Miiskein.     Vinli.  Arch.,    T)? 

Bd  .  1S78 
Jpiegelberg:  ^Iidtipel  auftretende  Knochensarkome.      Tnaiiir  -Diss.,    Fnil)iirg,    1S94. 
Sternberg:  .Myelom.     Verii.    d.  D.  path.  Ges. ,  vi.,  Jena,  1SI()4 
iteudener:  Beitnige  zur  Onkologie.     Virch.  Arch.,  r)9  Bd.,  is74. 
rillmanns:  IJeitr.^'z.  Lehre  v.  d.  Sarkomen.     Arch.  d.  Heilk.,  xiv.,  1S73. 
?rambusti:  Ban  u.  Theihing  d.  Sarkoinzellen.      lieitr.  v.  Ziegier,  xxii.,  1S9T. 
iirchow:  Die  krankliaften  Gcschwiilste,  2  Bd.,  1804. 
Vieland:  Primiir  niulliple  Knochensarkome.     Inaug. -Diss.,  Basel,  1H9:>. 
Villiams:    Histologic   u.   Ilistogeuese   d.   Utcrussarkoms.      Zeitschr.   f.   Heilk.,   iv., 

ls94(Lit.). 
eealso§§  114-116 

§  114.  Sarcomata  which   present  an  organoid  structure  ;ii)]i«^ar  in 

se  forms  known  ;is  alveolar  and  tubular  sarcomata.  TIhm'  aic  con- 
ective-t issue  tiiinois  iuwliich  llic  ('('llniar  cK'nicnts,  csjx'cially  the  lai},rcr 

s,  are  arranjjed  in  ijroiips,  so  that  it  is  jx^ssilde  lo  (li.stin<;uisli  a  ra.s- 
ilar  connrdivr-t'ismr  sfroina  and  .strands  or  vrst.s  of  cflls.  Accortlinj;  to 
leir  f^cnesis,  these  iirowtlis  may  l)e  di\  id<'(l  into  two  types:  /i/iiii>liiiiu/lnmir- 
nna  and  haiiuinf/io.sdrcoind.  There  aie,  however,  also  ahcoUir  sain-omala 
hieh  possess  stroma  and  cell-nest.s,  but  Mhicli,  in  so  far  as  their  devel- 
pnient  is  concerned,  cannot  ho  included  with  the  above-named  types. 

The  lymphangiosarcomata  are  tumors  which  arise  from  a  inoli/i  ni- 
bn  of  tlir  (ikIoIIk  llinn  of'  f/ir  Ijitnpli-vcssrlx  (1)1(1  hiinj)lixiuins.  They  n.ay 
pcordin^ly  be  desijinated  as  lymphangioendotheliomata  oi-  as  <•»//«;- 
rliomafa  in  the  narrower  Hcnsc.  Tiicy  ni:iy  dcx  »lo|»  rilher  in  previously 
jrmal  tissue,  or  in  ])i-eexistin^- tumoi-like  tonnal  ions,  .sncli  as  the  hy- 
?rtroi)hic  lymphan.uionia  in  ])articn]ar  (pi.umenled  moles  and  warts, 
ejjlOSj,  and  also  from  myxocliondroinala.     Tin'  lirst occur  ]>arlicularly 

the  meninges  of  the  brain,  and  in  the  wrous  mend)ranes  of  the  great 
Mly-cavities;    but  may  develoi)  also  in  other  organs;    the  secon«l  are 

und  chielly  in  the  skin;    while  those  arising  from  my\<tch Iromala 

ivelop  in  the  mixed  tumors  of  the  salivaiy  glands,  ]>alale,  an<l  orbit. 

The  mdoUirHoiiKitd  of  ihc  inner  )neninf/es  of  ihe  hniin  and  sjtiiiol  rord 
'Cur  partly  as  nodnlar"  growths  and  partly  as  llaltened  prolil<r;il  ions; 
'eydeveh')p  through  the  transformation  of  the  llallened  endothelium, 
iiicli  covers  the  connective-tissue  netwoik  of  the  sid)arachnoideal  tissue 
iid  pia,  into  cubical  or  even  cylindrical  cells  (Fig.  L'!»r>,  </,  r,.  In  con- 
fluence, the  new-growth  at  first  jjresents  th<'  appearance  tti' (/land  lib- 
,rmatiom;  in  the  event  of  a  more  active  prolileration  s(»lid  nests  tfrellH 
Jc  formed.  Inasmuch  as  the  i)ia  iscontinued  as  a  lymph  sheatli  around 
te  cerebral  vessels,  there  are  fornn-d  around  the  latti-r  str.in<ls  of  largo 
Jithelial-l ike  cells  (Fig.  21>.~.,  /',  </,  In. 


426  TUMORS. 

The  endothelioma  of  the  dura  mater  arises  through  a  proliferatiou  of  t] 
endothelium  of  the  lymph-vessels,  and  leads,  through  the  filling  up 
the  latter  with  large  cells,  to  the  formation  of  anastomosing  cords  of  ce" ; 
(Fig.  296,  c,  d,  e),  which  in  some  places  may  still  contain  a  lumen. 

The  endotheliomata  of  the  lileura  or  of  the  peritoneum  appear  usually  i 
flattened  thickeniugs  of  the  affected  membrane,  but  scattered  nodul- 
elevations  may  occur  throughout  the  areas  of  thickening.     These  growti 


^t^^ 


Fig.  295.— Section  through  an  endothelioma  of  the  pia  mater  and  cerebral  cortex,  diffusely  sprea(|ffir 
the  surface  of  the  brain  and  spinal  cord  (MiiUer's  fluid,  hiTmatoxylin).  a,  Superflcial  pia;  h,  pit :i  a 
sulcus ;  c,  cortex ;  cJ,  e,  endothelial  proliferations  in  the  pia  sheaths' of  the  cortical  vessels ;  /,  f/,  lu  lo- 
thelial  proliferations  in  the  pia  sheaths  of  the  cortical  vessels ;  i",  longitudinal  section  through  a  vein.     28. 

are  characterized  by  cords  of  large  cells  (Fig.  297,  h),  which,  corresp'jd- 
ing  to  the  course  of  the  lymph- vessels,  traverse  the  hyi)ertrophic  jod 
proliferating  tissue  of  the  serosa.  : 

The  endothelioma  of  the  mammary  gland  is  a  rare  tumor,  which  devc;P!^ 
in  the  form  of  nodules,  and  takes  its  origin  from  a  proliferation  of |h»' 
endothelium  of  the  lymph- vessels  and  lymph-spaces  (Fig.  298,  h,  c),p 
gives  rise  to  the  formation  of  large  cords  of  cells  (e)  or  of  smaller  ill- 
nests.  The  proliferating  cells  are  characterized  by  a  great  variatio  i« 
the  size,  character,  and  form  of  the  nucleus  and  cell-body. 

T\\i' endothelioma  of  the  skin,  which  arises  from  the  hypertrophic  m- 
])liangi()ina  ,' warts  and  pigmented  moles),  resembles  these  in  its  gejral 
structure,  and  possesses  afso  cell-nests  of  varying  size  (Fig.  277).  ur- 
ther,  thei'e  also  occur  endotheliomata  of  the  skin,  which  do  not  arise  om 
warts,  and  may  develop  in  great  numbers  (Spiegler,  Mulert). 

The  endotlu'lial proliferations  whieh  arise  in  myxomata  and  myxocho''ro- 
mata  fin-m  cords  of  cells  of  different  shapes  (Fig.  252,  h)  ;  but  it  sluW 


ENDOTIIKMOMA. 


42; 


be  noted  that  in  these  eases  simihirpiolilVratioiis  may  also  arise  from  tlie 

hlooil-vessels  (Fi.u.  ;>02.  c,  <1),  s.    thai  it  is  olh'ii   iiii|M)ssil)l(>  to  drcich' as 

to  the  naluii'  of  the  cell-st rands. 

j         The  alveolar,  tubular,  or  plcxiloiiu  si  ruct  niv  ..f  iho  •'iiilutlM-lioiii:t  is 

!  well  markeil  only  in  the  iirst  sta.ucs  of  iJir  lunior,  and  usually  disapprars 


Fig.  29t;.— Kndotlielionia  dura?  inatris  (Miillcr's  Iliiiil,  tia'inatnxvliti).  a,  ((iiiin'ciivi'-iissuc  stniinn;  /<• 
small-celled  fn.us ;  c.  L'luiips  and  strands  df  cells  arishiL'  fnmi  Ilu-  im.JifiTiiIii.n  cf  IvTnpli-vessel  endothe- 
lium;  (/.  endnthclial  I'cll-strand  with  a  Imncii  ;  «,  ana  of  fallv  (li'i:rMriail..ii  ni  ii.-st  of  endotlieiial  cells; 
/,  slraud  i<t  cflls.  passing  gradually,  on  tlie  figlil,  into  the  snrroiinding  conm-ctivi'  Ii>niii'.     ,-,  St. 

in  part  with  the  advancing  growth  of  (he  tuuKU'.     This  is  duo,  on   the 
one  hand,  to  the  fact  that  the  endothelial  proliferation  extmds,  without. 


vir*-<j^^>r>ii> 


po.  297.— Endothelioma  of  the  plenra  (alcohol.  ha>matnxylln).    a,  ProIlferat4'd  and  thickened  pleimil  r-..ii- 
I  ncctlve  tissue ;  /*,  cell-strands.    X  KK). 


pharp  liiuits.  iut 


'sharp  liiuits.  into  111.-  iiciuhlMuiug  couucitixo  tissue  (Fig.  2!M;,  _/'k  and, 
bn  the  (.thcr  hand,  to  the  cireuiustanco  tiial    tin-  ronn.'ct  iv. 'tissue  cells 


428 


TUMORS. 


take  on  a  proliferative  activity  similar  to  that  of  the  endothelium,  s 
that  there  is  formed  a  diffuse,  cellular  new  growth  of  the  character  c 


Fig.  298. — Endothelioma  of  the  mammary  gland  (alcohol,  haematoxylin.  eosln).    a.  Connective  tissue; 
enlarged  cells  in  the  connective-tissue  spaces  ;  c,  strands  of  cells ;  d,  diffuse  cell-proliferation,    x  300 

an  ordinary  sarcoma  (Fig.  298,  d).  Accordingly,  the  endothelioma 
cannot  be  sharply  distinguished  from  the  sarcomata,  and  may  becoii 
transformed  into  the  latter. 


The  similarity  in  structure  between  endotheliomata  and  carcinouiata  raises  ii 
question  whetlier  "it  would  not  be  expedient  to  class  the  former  us  endotJielial  cana* 
The  structure  of  these  tumors  would  certainly  justify  such  a  classification,  hut  I  ci[ 
sider  it  better  to  avoid  the  use  of  this  term.  In  the  first  place,  the  term  endothelio  ^ 
is  in  general  use  and  is  entirely  appropriate,  and  the  introduction  of  the  term  endot  ■ 
lial  cancer  would  easily  give  rise  to  confusion;  by  the  term  cancer  in  general  is  und- 
stood  an  epithelial  tumor,  and  it  does  not  seem  expedient  to  introduce  two  types? 
cancer — an  epithelial  and  an  endothelial.  j 

I  have  classed  as  endotheliomata  those  tumors  of  the  serous  membranes  which  'j 
characterized  by  the  formation  of  cell-cords  in  the  lymph  channels,  on  the  assumpt  i 
that  these  cords  of  cells  arise  from  the  endothelium'of  the  lymph-vessels  and  lym  }- 
spaces.  I  must  admit,  however,  that  I  do  not  consider  this  assumption  as  absolut*' 
proved,  in  spite  of  the  concurring  definite  statements  of  a  number  of  authors  (^ 
Glockner).  The  possibility  of  their  development  from  the  epithelitmi  of  the  seros:8 
not  excluded  (Benda),  and  if  such  an  origin  could  be  proved,  the  question  would  a  3 
whether  it  would  not  be  better  to  class  these  tumors  with  the  carcinomata,  since  3 
corresponding  tumors  of  the  kidneys  and  ovaries,  whose  gland-cells  arise  from  p  - 
toneal  epithelium,  are  classed  with  tlie  epithelial  tumors. 

According  to  investigations  by  J/.  B.  Schmidt,  the  cellular  elements  of  the  sai;- 
mata  of  the  dura  mater,  as  well  as  of  the  psammomata  (§  116),  that  for  the  chief  \  t 
are  located  in  the  neighborhood  of  the  dural  sinus,  arise  from  endotheJial  cclh  of  ,e 
tinichnoid  that  under  physiological  conditions  are  pushed  into  the  tissue  of  the  duraQ 
part  by  the  ingrowing  Pacchionian  bodies,  and  in  part  as  independent  cell-plugs  fJin 
the  smooth  surface  of  the  arachnoid.  ' 

Literature. 

(Endothelioma  [^LymphangiosarcomcC] .) 

Adler:  Primary  Endothelioma  of  the  Pleura.     Jour,  of  Med.  Res.,  1901. 
Barth:  Lymphangiosarkom  d.  Mundbodens.     Beitr.  v.  Ziegler,  xix.,  1896  (Lit.). 
Benda:  Prinuires  Carcinom  d.  Pleura.      Deut.  med.  Woch.,  1897. 
Bdhme:  Primiires  Sarko-carcinom  der  Pleura.     Virch.  Arch.,  81  Bd.,  1880. 
Borrmann:  Endotheliome.    Ergebn.  d.  alli;-.  Path.,  vii.,  AYiesbaileu,  1903  (Lit.). 


EXDOTIIKLIOM  A. 


429 


Endotlielio 


Beitr.  v.  IJiims,  3(1  Hil.,  lliOS  (Lit.). 


iiber  glykogoureichc   EiidotlielioiiK-.       Bi-ilr.  v,  Zio"-l 


gici 


Knddtlic'lioine.     Virc-li.  Airli.,  153  Hd. 
la  Pk'uia.     A.  per  \v  Sc.  Mrd..  xxvi.. 


1S9S. 


a:  EiiduMiL'liome  d.  Lyinplidruseii  u.  LyinphbaliiR'ii.    V.  A., 
rdt:  Kndotlicliom  del- Pleura.      Iiiaug.-Diss.,  Frcihiiri.',  18!)4. 


Cd..  1903. 


(Lit): 


Burkhard:  Sarkom  i 
Driessen:  I'litcisiuli 

Eberth  u.  Spude:  Faiiiili 

Ferrio  v  Orevere:  Eiidot. 

Gallina: 

Gebhardt:  Kndotlicliom  dcr  I'lcura.      liiau;?. -Diss.,  Frcihiir-.',  18!)4. 

Glockner:  Kiidotlu'lkichs  d.    scri'iscn  Haute.     Zcitsclir.    f.    Hciik.,  xviii.,  ISOI 

Hiescnzellcn  u.  endothcliale  Gescliwiilste.     Bcitr.  v.  Zieijlcr,  xxvi.,  lS!»i(. 
jKelly:  The  Histolou:y  and  IIisto,-;encsis  of  Certain  Tumors  of  the  I»a'rolid,  with  Par- 
'        tieular  Reference  to  Those  ul'  Emlothelial  Uriirin.     Phila.   Month    ,Med    Journ 

ISit'.l. 
Kromayer:  Endothelioma  tuberosum  colloides.     Vircli.  Arch..  V.V.t  F,d.,  1895. 
Krompecher:  Endotheliom  des  Ilodens.     Virch.  Arch.,  l.")l  J5d.,  .Suppl.,  1898. 
Kuttner:  (Jcschwiilste  der  Submaxillaris.     Beitr.  v.  Bruns,  xvi.,  189G  (Lit.). 
Lancereaux:  Traite  d'anatoniie  pathol.,  iil.,  I'aris,  1889. 

Linser:  Vcrkalkte  Epitheliome  uud  Phidotholiome.     Beitr.  v.  Bruus,  xxvi.,  1900. 
'Marchand;  Endotheliom  d.  Antrum  Ilighmorl  mit  hyal.  KuKcln.     Beitr.  v.  Zicclor 
'        xiii..  1S93.  .  fe  b     . 

Mulert:  .Multiple  Endotheliome  der  Kopfhaut.     Langenbeok's  Arch..  .")4  Bd.,  1897. 
Neumann,  E. :  Ueber  Sarkome  niit  endotheliulen  Zelleu.     Arch.  d.  Ileilk.,  xiii.,  1872 
V.  Ohlen:  Beitr.  z.  Kenutn.  d.  Parotisgeschwiilste.     Beitr.  v.  Ziegler,  xiii.,  1893. 
|Perls:  Beitr.  z.  Gesclnvul.stlehre.     Virch.  Arch.,  56  Bd.,  1872. 
iPerthes:  Verkalkte  Endotheliome.     Beitr.  v.  Bruns,  xii.,  1894. 

PoUmann:  Endotlieliom  d.  Pleura  u.  d.  Peritoneums.     Beitr.  v.  Ziegler,  xxvi.,  1899. 
iRitter:  Fettgehalt  der  Endotlieliome  d.  Knochen.     Zeitschr.  f.  Chir,  50  Bd..  1899. 
Rossier:  Cancer  primitif  de  la  plevre.     Beitr.  v.  Ziegler,  xiii.,  ISit.S. 
Schmidt:  Pachion.  Grauul.  u.  Sarkome  (L  Dura  mater.     V.  A..  170  Bd. ,  1902. 
Schulz,  R. :  Das  Endothelcarcinom,     Arch.  d.  Heilk.,  xvii.,  1876. 
Tanaka:  Endotheliome  (bes.  d.  llaut).     Deut.  Zeitschr.  f.  Chir.,  51  Bd..  1899. 
Teixeira:  Zur  Casuistik  des  primaren  Pieuraendothelionis.     Inaug.-Diss.,  Freiburg. 

is't4. 
Volkmann:  Eudotheliale  Geschwillste.     Deut.  Zeitschr.  f.  Cuir.,  41  Bd. 
Waelsch:  Aus  weichen  Naevi  entsteh.  bOsart.  Geschw.     Arch.  f.  Derm., 


,  1895  (Lit.). 
49  Bd.,  1899. 


jWarthin:  Endothelioma  of  the  Lachrymal  Gland. 
1        See  also  ^g  113  and  115. 


Arch,  of  Ophth.,  1901. 


§  115.  The  haemangiosarcomata  represent  a  group  of  organoid  sar- 
comata, in  which  the  walls  of  the  blood-vessels  and  their  siirronndiiig 


-Blood-vessel  endoth'»llonia  of  the  kJdnev   (formalin,  hipmatoxylln,  eomn). 
with  blood ;  b,  vessels  fllled  wilh  proUteraled  endothelial  cella.    X  JW. 


430 


TUMORS. 


tissue  take  au  especial  part  in  tlie  building-up  of  the  tumors,  and  cor 
stitute  a  characteristic  feature  of  their  structure. 

One  form  of  htemangiosarcoma  is  the  blood=vessel=endotheIioma  c 
hasmangioendothelioma,  a  tumor  which  arises,  either  from  preexistin 


Fig.  300.— Section  through  a  nodular  angiosarcoma  of  the  thyroid  (Fleniming's  solution,  safranin).  i 
Transversely  cut  vessels  ;  b,  perivascular  cylindei-s  of  cells  cut  transversely  and  sho\\  mn  numerous  mitosi 
c,  granular  masses,  with  scattered  cells,  between  the  cell-cylinders.    X  73. 

blood-vessels  or  those  newly  formed  in  htemangiomata,  tlirough  a  mo: 
active  development  and  proliferation  of  the  endothelium  giving  rise  j 


Fig. 301.— Angiosarcoma  of  the  testis  (Miiller's  fluid,  lui'in.itdxylin,  eosin).  «,  Perivascular  masse* 
clofely  packed  cells  ;  /),  areas  poor  in  cells ;  c,  hyaline  lumps ;  d,  hyaline  masses  containing  blood  ;  e,  a>  -• 
nlferous  tubules ;  /,  large  vein.    X  80.  ' 


iI.KMA\(;i()SAK(<).MA. 


i:;i 


nlood-vessel  r.paeos  lined  Avith  oubicjil  (tr  cyliiulricnl  ciKloliiclinii)  (  l-'i;^. 
2!>9,  <0,  or  to  canals  coinplctrly  iilU'd  with  such  cells  (/n.  According-  t<> 
ihe  munber  of  bUiod-containinj;-  vessels  the  tumor  is  »'ithcr  «lark-icd, 
tude,  «>niyish-\vhite  or  yellowish-Mhite.  The  eiidolhclial  cflls,  according 
\o  the  stajic  of  development,  may  contain  <;lyc(»ncii  oi'  I'at  oi-  bolh. 
'  A  second  form  o'i  liaMuanu,ios;ircoma,  the  hjcmaniriosarcoma  in  ;i 
liarrow  sense  (occasionally  also  called  pcritliclionni },  uriscs  tlir(»uj;h  the 
troliferation  of  the  tissue  of  the  outer  layers  (►f  the  blood-vessel  walls 
;nid  their  immediate  surroundinji;s,  so  that  the  vessel-hnniiia  are  sur- 
rounded by  a  more  or  less  thick  mantle  of  cells  {V'\ii.  'MO,  h  ). 

In  tyi)ical  cases  the  tumor-tissue  consists  almost  wholly  of  a  cnnfuscd 
antrle  of  blood-vessels  (Fig".  300,  a),  whose  Avails  ai-e  suri-camdcd  I)y  a 
hick  layer  of  cells,  which  often  reach  to  tlu^  endothelium.  ^Fhe  thick- 
ivalled  tubes  of  cells  sometimes  run  an  isolated  couise,  and  at  other  times 
mastomose,  so  that  variously  formed  twistings  and  intt  r\\»  ax  iims  icsnlt 


Fi<i.  a(i2.-  (■hoiKlrolihroiiiu  of  the  parotid  with  aiigiosarcoiua  (Mulli-r's  Ihiid.  h;fiiiatoxylin.  i-<>sliii.  u. 
■WW  of  cartilafre ;  h,  dense  sarcoma  tissue :  c,  blood-vessel ;  d,  cell-strands  uiislnjf  from  IjlwKl-vi-jewLs.  and 
part  containing  a  hyaline  substance.    X  80. 


plexiform  anfjiosanviiKi ).  The  tissue  lyiii^i"  bctwrcii  lin-  (cIl  sir 
le  remains  of  the  oii-inal  tissue  (Fiji'.  ;{(H,  />  i,  aii<l  may  si  ill  < 
uiracteristic  tissue-formal  ions,  as,  for  example,  glands  (r  i. 

Should  a  more  active  proliferation  (»f  tlu-  itcrivascular  maiillc 
■cur,  and  if  these  become  conllueiit  with  each  other  (Fig.  :{0l)  the 
usses  over  into  an  ordinary  sarcoma.  This  change  almost  iiiv 
■curs  in  the  larger  tumors  of  this  kind. 

HaMiiangiosai('(»mata  occur  in  the  most  Aaiicd  or^xans:    tcsti<-h 
iys,  salivary  glands,  bones,  brain,  mamma,  tliyn 
>ccygeal  gland,  ovaries,  and  liver.      In  the  last- 
rc.      I'.oih  forms  mav  so  occur  that  the  tumor  tin 


1,  skill,  carotid 
lined  (.igans  th 
uirliniit   bears  Ih 


inds  is 

niitain 

.f  •■ells 

tumor 

iriably 

s.  kid- 

gland, 

ev  are 
.•"ehar- 

432 


TUMORS. 


acter  of  a  liiBmaiigiosarcoma ;  but  it  also  Lappeus  that  such  proliferatid 
of  the  vessels  form  ouly  a  single 
feature  of  other  tumors  CFigs. 
302,  c,  d;  311,  d);  aud  though 
this  feature  indeed  gives  charac- 
ter to  individual  portions,  it  is,  ou 
the  whole,  overshadowed  by  other 
features  of  the  growth — as,  for  ex- 
ample, a  fibro-cellular  tissue,  car- 
tilage (Fig.  302,  a,  h)  or  myxo- 
matous tissue  (Fig.  311,  a). 

Lymphaugiosarcomata  a  n  d 
hseraaugiosarcomata  cannot  al- 
ways be  sharply  differentiated 
from  each  other,  and  tumors 
occur  to  which  both  designations 
may  be  applied  with  propriety. 
The  perivascular  develojjment  of 
the  eudothelial  proliferation  with- 
in the  brain  iu  endothelioma  of 
the  pia  (Fig.  295,  /,  g,  h)  would 
justify  also  the  application  of  the 
term  htemangiosarcoma. 

If  iu  a  lymphangiosarcoma  of 
the  skiu  there  is  such  a  rapid  de-  ; 

velopment  of  the  cell-uests  that  the  space  between  the  vessels  becop 
wholly  filled  with  cells,  so  that  the  framework  of  the  tumor  comeiibo 
consist  only  of  blood-vessels  (Fig.  303),  it  becomes  an  open  questio]|aa 
to  whether  the  tumor  should  be  called  a  lymphangioendothelioma  O'  a 
hsemangiosarcoma.  ' 

Borst,  in  his  work  on  tumors,  hasentirely  separated  the  endotheliomata  (lymphaijO- 
and  hsemangio-endothehoma)  from  the  sarcomata,  and  has  attempted  to  class  the  las 
an  especial  form  of  neoplasm.  In  so  far  as  typical  microscopical  pictures  are  conceii4, 
such  a  separation  is  indeed  possible,  but  the  endotheliomata  in  general  do  not  she, in 
all  portions  so  typical  a  structure  that  they  can  be  distinguished  from  ordinary  sifO- 
mata.  Further,  it  is  by  no  means  determined  that  endothelial  cells  of  the  lyr'h- 
spaces  and  vessels  do  not  take  part  in  the  formation  of  sarcomata.  It  seems  to;|e, 
therefore,  better  to  consider  the  endotheliomata  as  an  especial  form  of  sarcomin 
which  the  structure  of  the  tumor  still  permits  us  to  see  that  undoubted  endothelial  Ills 
give  rise  to  the  cell-masses.  I 

Literature. 

I 

( Hcvm angiosarcoma  [En doth elioma'] . )  j 


ru.    303  — Ahdilai  iiH  lanotio  sateonia  of  the|in 
(.lUohol,  li  iinatowlin)     <(,  Monouuolear,  a„  n|tl- 
iiiK  K  ai  saMdiiifi  (f  IK  of  epitlulial  character;  '^  - 
iiK  nt  (ont  iiniiijr  cells;  t,  stroma  with  blood-v 
ami  pigment      ^  5(K) 


[-V(^ 


Beitr.  v.  Ziegler,  viii.,  1890.  ] 

Arch.,   151    Bd.,   1898;    Wachsthu:, 

Beitr.  v.  Ziegler,  xxxiv.,  1902.        j 


Arnold:  Primiire  Angiosarkome  der  Leber. 
Borrmann:   Blutgefiissendotheliom.     Virch 

Gefiissgeschwiilste.     lb.,  1.57  Bd.,  1899. 
Colmers:   Sarkom  u.  Endotheliom  d.  Penis, 

Franke:   I']ndothelioma  intravasculare  hyalogenes.     V.  A.,  121  Bd.,  1890 
Frattin:   Endoteliomi  dei  vasi  sang.     A.  per  le  Sc.  Med.,  xxv.,  1901.  i 

de  Haan:  Angiosarkom  d.  Leber.     Beitr.  v.  Ziegler,  xxxii.,  1903.  , 

Hansen:  ILcmangioendothelioma  uteri.     Virch.  Arch.,  171  Bd.,  1903. 
Harris:  Malignant  Disease  of  the  Pleura.     Journ.  of  Path.,  ii.,  1893.  ! 

V.  Heinleth:    Perithelioma  gland,  caroticae.     Cbl.  f.  allg.  Path.,  xi.,  1900.  ; 

Hildebrand:   Tubuliires  Angiosarkom  der  Knochen.     Deut.  Zeitschr.  f.  Chir.,  SlMv 

1890;    Nicrentumoren.     Arch.  f.  kHn.  Chir.,  47  Bd.,   1894. 
V.  Hippel:    Zur  Casuistik  der  Angiosarkome.     Beitr.  v.  Ziegler,  xiv.,  1893. 
V.  Hleb-Koszanska:   Peritheliom  der  Steissdriise.     B.  v.  Ziegler,  xxxv.,  1904.   , 
Jarisch:    Ilautgeschwulste  (Hamangioendotheliom).     Arch.  f.  Derm.,  28  Bd.,  ■94. 
Jolly:   Angiome  sarcomateux.     Arch,  de  med.  exp.,  vii.,  1895. 
Kolaczek:   Uel)er  das  Angiosarkom.     Deut.  Zeitschr.  f.  Chir.,  ix.  and  xiii. 
Limachet:   Blutgefiissendotheliom.     Virch.  Arch.,  151  Bd.,  Suppl.,  1898. 


MELANOSAIUO.MA. 


iXi 


.Iniirii.  of  Mel.  H.vs.,  I'.urj. 
Hcitr..    Icstsc-lir.    f.    Virrl...w.    ii. 


Low  and  Lund;    Tul>ul;ir  Porivascular  Siircurii.i 
tfarchand:    Anat.   d.   (ihindvila    carotica.      liil. 

IS'.li. 

ffarkwald:   Multijil.  iiitravaskulares  ICiulotlirliom  d.  Knoclicii.     W  A.,I11  Hc|..  isoo. 
»Iarx:    Tunior  der  Leber.     Beitr.  v.  Ziepler.  xxxvi.,    I'.HH. 
llaurer:   Heiti.  z.  Kenntniss  des  Aii<:i().s;irkoin.s.      Nircli.    Aieli.,  77  Hd.,  l.S7<,». 
'altauf :   Cescliwiilste  tier  GlaiuUila  caroticix  (Anfiiosjirkom).     Heitr    v     Ziculcr    xi 

1S92. 
e  Paoli:    Priiiuires  Ansiosarkom  der  Niere.     Beitr.  v.  Ziejiler.  x.,  1S<,M. 
lindfleisch  u.  Harras:    llndotlieliom  d.  Kiioclieiimarks.     V.  A.!  lO.i  Bd..  ISSd. 
litter:    rctthaitiLres  Ijiddtheiioin  der  Knoehen.     Zeitsclir.  f.  Chir..  ")()  Bd.,'  1S<»'.». 
iailer:    rriinary  luulothelionia  of  Left   Sup.   Piiliii.   \'eiii.     Cont.  from    the    \\illi'im 
,       IVpper  Labor..  1900. 

pchmidt:  Ueher  das  Angiosjukoin  der  .Maniina.     Arcli.  f.  kliii.  Cliir..  :{ti  lid.,  1SM7. 
waldeyer:  Die  Eiitwickelung  der  C'arcinoiiic.     Vinli.  Anli..  .",.",  |'„|..  isT'J. 
Volters:  Haemangioendothelioma  tuberos.  inuilipicx  cutis.     Ar(  ii.  (.  Derm.,  .■>:!  Bd., 

litOO. 
[      See  also  5^^  114  and  116. 


;<  116,  Sarcomata  which  acquire  a  peculiar  character  through 
special  products  of  the  cells  or  through  changes  in  their  ground- 
ubstance  are  to  be  found  l)otli  :imoiii;tliesiiiii)leaii<l  tlicoitiaiioid  I'oiins. 
i'he  chief  types  belougiiig  in  this  clas.s  are  the  niehmosjircoina,  chloronia, 
steosjirconia,  osteoid  sarcoma,  the  petrifvin<;  .sarcoma,  psammoma,  and 
lie  .sarcomata  containing;  hyaline  format ion.s. 

Melanosarcomata  occur  in  ti.ssues  wliich  contain  ])i<;iii('nt«'d  comicc- 
ive-tissue  celL"^ — chromatoplioir.H.  They  (U'veloj)  most  li('(|nt'iitly  in  the 
ihoroid  of  tlie  eye  and  in  the  skin.  Jn  the  hitlei-  case  they  arise  eldetly 
jrom  pigmented  moles  and  lentigines.  They  l»eh)ng  to  the  malignant 
Hrcomata,  grow  into  the  neighboring  tissues,  and  give  rise  to  niela.sta.ses. 
fhe  fully  developed  tumor  is  in  whole  or  in  part  smoky  gray  to  black  or 
|rownisii-l)lack,  the  color  being  due  to  the  ])resence  of  round,  angular, 
iusiform,  and  branched  cells,  which  are  tilled  with  yellowish-brown  pig- 


30C— Melanotic  sarf< 
Desis; 


.flti.-sk 
[)i^:iii.-iit-< 


Inn,  poHin).    a,  :^rroinn  (Dmur  rich  In  cells;  b,  eMU 
s.sels  with  hyullne  wulls.     -•-  'MK 


434 


TUMORS. 


ment  grannies  (Fio-s.  304,  b,  e ;  305,  <-),  or  are  stained  a  diffuse  yelar. 
In  the  alveolar  forms  both  the  large  cell-nests,  as  well  as  the  smaller  lis 
of  the    supporting    framework,    may   contain    pigment.       It   is   c|u 


.  ^ '  ,=.-^  « 


V-;.-v  ii'4;^V -^-^vv     ."*'   > 


Fig.  305.— Metastasis  of  a  melanotic  sarcoma  of  the  slvin  In  the  mesentery  of  the  small  intestine  ('ma- 
Iln,  alum-carmine).    «,  Peritoneum  ;  h,  fat  tissue  ;  c,  sarcoma  nodule  ;  d,  isolated  chromatoi)hores.    '2Pn. 


^'?f «^f<^^-^'^??^^' W'~':^P^- w^?'  :;§^ '  { 


^    V? 


»  ^  '^^  *^  x^^- — i^pdo-sleaf  ()  t  ()  u  onii  of  tht  humerus  (t'oimaljn,  nitric  acia,  nsema  cyl'i. 
ana  eosin.)  a,  Old  bony  tuibtcuLi  of  the  sponKiOha,  b,  sarcomatcjo  pr>.,Lf^ration  arising  fio  Hie 
endosteum;    c,  Cj.  new-formed  bone;    d,  blood-vessel.     X  SO. 


CIILOKCMA.  435 

especially  abundant  in  tlio  neijiliborluxul  of  tlio  l»l<MMl-\rsscls  (Fi<;s.  ;{(»;{, 
<■;  304.  <));  but  this  i)i<;iMon(  is  not   lui'mosidcrin. 

The  metastases  are  likewise  more  or  less  i)ii,Mii('nb'(l  (  Fi«;.  -MKt) ;  and 
the  smallest  ones  may  consist  essentially  of  i)i«,nneiitrd  cells (r,  </),  Cases 
occur  in  wliicli  numerous  oriians,  the  skin,  muscles,   i)ia,  serous  mem- 


.'■-V'  '-'   -  'i-'"'  •  -  •v;*'.*»^-\'^'  .:"•-.".,        ,>*.,"-   .\'' f^ ''' '-  ".'.*.' 


Fig.  307. — Sarcoma  ossificans.     (Formalin,  nitric  acid,  liajmatoxylin.  and    |)icrofucli.-^in.)    u, 
Sarcoma  tissue;    b,  new-formed  bone;   c,  areas  of  transition.     X  40. 

)ranes  and  adii)0se  tissue  (Fig.  305)  are  sitotted  Itlack  ilirou-h  tli<-   f<>i- 
nation  of  innumerable  metastases, 

Chloromata  are  tumors  the  cut  .suiface  of  which  jtresenls  :i  lij^ht- 
;reen  color  which  on  exi^osure  to  the  air  takes  on  a  dirty  appearaneii. 


6.  3(10.— Osteoid  saivoma  of  the  rthmold  bono  iMnllei  «  num.  Iiu'inaloxylln.  ••««ln).    n.  J^unxjina  'intuu; 
b.fi8teolf)  ti.ssue;  f  old  l)on<--trat)^riilif:  i/.  vii.wnilur  llliroiis  IKmui!.     x  «.». 


436 


TUMORS. 


They  develop  most  frequently  from  the  periosteum   of  the  craniui; 
and  consist  of  tissue  made  up  of  round  cells  and  a  reticular  stroir 


Fig.  309. -PetrifyiuK  laiKe-<elk'd  sarcoma  of  the  tibia  (Miilk'i's  tluul,  liaMiiatoxylin,  eosin).  a,  F|'. 
morphous  tumor-cells;  /;,  alveolar  stroma;  c,  trabecular  of  struma  containiug  small  calcareous  con  > 
tloas ;  d,  petrifying  trabeculae  of  the  stroma.    X  330.  • 


They  may,  therefore,  be  classed  with  the  lymphosarcomata.  They  mjjr 
be  associated  with  a  lymphsemia.  Eeceut  studies  (Warthiu,  Klein  ad 
Steinhaus,  etc.)  show  that  chloromata  are  primary  tumors  of  the  bo;- 
marrow,  arising  from  the  parent-cells  of  the  white-cells.  Some  confjt 
chiefly  of  myelocytes,  either  neutrophile  or  eosinophile,  while  others  :|e 
composed  of  cells  resembling-lymphocytes.  There  is  usually  an  asscj- 
ated  leukiemic  condition  of  the  blood.  : 

According  to  Cliiari  and  Gruber,  the  green  color  is  due  to  the  prese  'e 
in  the  cells  of  small  shining  spherules  which  give  the  microchemiil 
reactions  of  fat.  In  harmony 
with  this  view  is  the  fact  that  the 
color  disappears  in  alcohol.  On 
the  other  hand,  von  Reckling- 
hausen holds  that  the  color  is  a 
property  of  the  parenchyma  and 
that  no  morphological  elements 
are  the  carriers  of  the  color. 

Osteosarcomata  or  ossifying 
sarcomata  occnr  chiefly  in  con- 
nection with  the  skeleton  and  are 
characterized  by  the  new-forma- 
tion of  bone  within  sarcomatous 
tissue.  The  new  bone  arises  at 
times  from  a  thick  homogeneous 
ground -substance  {c,  c^  formed 
between  the  tumor-cells  (Fig. 
306,  6)  which  is  either  connected 
(c,)  with  the  old  bony  trabeculse 
(a)  or  arises  independently   (e), 

or  at  other  times  from  a  coarsely  fibrillated  connective  tissue  (Fig.  7, 
c)  Mhich  gradually  becomes  condensed  (i)  and,  taking  up  lime-salt  is 
transformed  into  bone. 

Osteoid  sarcomata  develop  in  the  endosteum  and  periosteum,  ud 


;^_^^ 


:^^-:' 


Fig.  310.— Section  from  a  psaramoma  of  the  'ira 
mater  (alcohol,  picric  acid,  hivmatoxylin,  eosin  a. 
Hyaline  nucleated  spherule  inclosing  calcareous ,'n- 
cretion:  /<,  calcareous  cdncrction  with  liyalinc  'M- 
nucleated  border,  inclnsed  iu  ilbrnus  counecii'  i-- 
sue;  c,  calcareous  c(iiicietiiin  surmunded  liv  li  '"'' 
connective  tissue;  <?,  spicule  of  liuie  in  the  ci  '^■• 
live  tissue;  e,  spicule  with  three  concretions.     ,'*'• 


PSA.M.MO.M.V. 


437 


are  charrtcterized  by  a  thiokoninj;  o(  the  frroniid-siihstiinco  in  certain 
iiivas,  so  that  there  are  fornunl  trdhrciilic  of  osttoid  ti.s.si(c  ( I'i^r.  .'{OS,  />). 
Such  tunittrs  arc  closely  related  to  \\w  osteosaicoinata,  hut  dilVcr  I'nuu 
tlicni  iu  the  ahsence  of  deposits  of  Ihue-salts. 

Petrifying  sarcomata  likewise  occur  most  fretjuenlly  in  connection 
with  tiie  skeleton,  and  are  characterized  by  the  (le\  elopnient  l»«'tween 
the  tunn)r-cells  of  tralx'cuhe  of  a  delicate  liroinid  snl)slance  (  l-'ii:.  .'{0!», 
••),  through  the  adrifU'diion  {d)  of  which  the  tuniui-  tissue  heci.nies  hanl- 
Mied,  althon.uh  no  tyi)ical  bone  is  formed. 

Psammomata  or  ,s(i)id  tumors  (acervulomata  )  are  sai'c«»mata  ur  lihm 
^ircomata  of  thedui-a,  inner  ineinnj;-es,  or  pineal  ^land,  which  contain 
•oticrrlions  of  liiiif'-'<<dt.s  in  greater  or  less  abundance.  Some  of  these  cun- 
•retions  are  similar  in  stiuctnre  to  the  ncuinal  brain-sand,  the  basis  of 
heir  formation  being- concentric  layei-s  of  cells  which  ha\e  nndergone 
lyaline  degeneration  (Fig.  810.  a,  />,  <•).  Occasionally  tiie  chalky  sphci- 
lics  lie  inside  of  individnal  cells  and  represent  hyaline  i)ro(lucts  of  tiie 
•ells  which  have  later  become  calcitied.  Others  are  moie  of  the  nature 
i)f  spicules  (>/),  and  arise  through  tlie  deposit  of  lijne-salts  in  connective 
fissue  or  blood-vessels  which  have  undergone  hyaline  degeneration. 


Fig.  311.-Myxo-anKiosarcoma  of  the  parotid,  with  hyaline  foniiatlons  (MQllt-r's  lliiUl.  Iin-niiil"xylln. 
sin),  a.  Myxomatous  tissue;  }>.  cell-strands  inelosinp  hyaline  spherules:  <•.  hyaline  xpherules  In  inyx«»- 
atous  tissue;  (/,  blood-vessels  with  proliferatinn  en<loIlieliiini  and  hyaline  spherules.         IMt. 


Psammomata  usually  form  i-ound  nochiies,  and  ni;iy  lie  i.f  iiiiilti|ih- 
currence. 

Sarcomata  with  hyaline  formations  (the  myxosan  nmaia  excepted  i 
ise  as  follows:  Either  the  alls  form  lii/olinr  produrts.  or  tin//  tlo  msrlns 
rome  convciird  into  such,  or  the  fidhf  ilmloprd  connrrtirr  tissitr  and  tin: 
md-vcHscls  undf-rt/o  hijoliur  dcf/cncndion.  These  changes  ma\-  t;ike  place 
simple  sarcomata  as  well  as  in  endolheliom:ita  and  ha'niangios:ircom;ita  ; 


438  TUMORS.  I 

but  occur  much  more  frequently  in  the  last-named  tumor-forms  (FiL 
307,  &;  302,  d:  311).  The  hyaline  masses  may  form  spherules,  orch»- 
like  forms,  or  cords,  or  net-like  or  cactus-like  figures.  They  push  ie 
cells  apart,  and  often  reduce  them  to  narrow  strands.  Billroth  has  ci|;- 
ignated  sucli  tumors  as  ci/lindnmata.  In  endotheliomata  the  hyaline  ••- 
geiiei'ution  may  be  associated  with  the  formation  of  Jaminuted  masses^ 
Jiatiencd  crU.s  like  the  lai/crs  of  an  onion,  around  a  nucleus.  { 

Jlyaline  degeneration  of  the  ces.sel- walls  and  of  the  connective -tissue  bum^g 
results  in  a  thickening  of  the  same  (Fig.  304,  d),  sometimes  uuiforDy 
and  sometimes  irregularly  distributed.  Hyaline  products  of  cells  havia 
tendency  to  assume  a  spherical  form  (Figs.  297,  b;  302,  d;  311,  c,  '). 
The  disintegration  of  larger  cell-masses  with  hyaline  change  leads  to  je 
extensive  formation  of  hyaline  spherules,  strands,  or  branching  str>,- 
tures.  I 

If,  in  endotheliomata  and  angiosarcomata,  the  cord-like  masses  if 
cells  which  have  been  formed  within  the  lymph-  or  blood-vessels  becOiC 
converted  into  hyaline  masses,  there  will  be  produced  formations  whjh 
greatly  resemble  glands  containing  colloid  (Fig.  311,  d) ;  and  wblli 
have  often  been  mistaken  for  such.  i 

Ribbert  regards  the  melanosarcoma  as  an  especial  form  of  tumor  arising  fron;!tie 
chromatophores,  and  would  for  this  reason  separate  it  from  the  sarcomata  as  an  indijd- 
ual  tumor-type.  It  is  to  be  nutcd,  Imwever,  that  in  the  development  of  the  melai;.ic 
sarcoma  other  cells  besides  the  ell II iniatoj^liores  take  on  proliferative  activity;  so  !at 
melanotic  sarcomata  can  be  regarded  only  as  sarcomata  in  whose  development  cei.in 
cells,  which  possess  the  power  lo  form  pigment,  have  taken  part.  j 

I 
Literature.  j 

{Melanotic  Sarcoma.)  \ 

Achenbach:  Orbitales  Melanosarkom.     Virch.  Arch.,  143  Bd.,  1896.  ! 

Derby:   Melanosarkom  d.  Ciliarkorpers.     Mon.  f.  Augenheilk.,  1903.  j 

Dietrich:  Beitr.  z.  Statistik  u.  klin.  Bed.  mel.  Geseh.  Arch.  f.  Id.  Chir..  xxv.,  lii?. 
Dobbertin:    Melanosarkom  d.  Kleinhirns.     Beitr.  v.  Ziegler,  xxviii.,  1900.  i 

Gonin:   Sarcome  pigmente  de  la  cornee.     Beitr.  v.  Ziegler,  xxiv.,  1898.  ' 

Hirschberg  u.  Birnbacher:   Sarcoma  melan.  corp.  cil.  et  chorioideae.     Cbl.  f.  Aun- 

heilk.,   1884. 
Just :   Ueb.  d.  Verbr.  d.  mel.  Geschw.  im  Lymphgefasssystem.     I.-D.,  Strassburg,  ]%%. 
Katsurada:   Pigmentierung  der  Kapillarendothelien.     B.  v.  Ziegler,  xxxii.,  1902| 
Kayser;    Irissarkom  entst.  a.  e.  Naevus.     Mon.  f.  Augenheilk.,  1903. 
Leber:    Aderhautsarkome.     Arch.  f.  Ophthalm.,  44  Bd.,   1897. 
Martens:   Entwick.   d.  Melanosarkoms  d.  Chorioidea.     Virch.  Arch.,   138  Bd.,  iH. 
Maurer:   Beitr.  z.  Kenntniss  der  Angiosarkome.     Virch.  Arch.,  77  Bd.,  1879.         | 
Mdrner:    Zur  Kenntn.  d.  Farbstoffes  in  melan.  Geschw.     Z.  f.  ph.  Chem.,  11  Bd.,  ]ji7. 
Oppenheimer:   Pigmentbildung  in  melanot.  Geschw.     Virch.  Arch.,  106  Bd.,  ISj. 
Putiata-Kerschbaumer:    Das  Sarkom  des  Auges,  Wiesbaden,  1900.  ' 

Ravenna:    Ilistogenese  d.  melanot.  Geschwulste.     V.  A.,  171  Bd.,  1903.  : 

Ribbert:    Das  Melanosarkom.     Beitr.  v.  Ziegler,  xxi.,  1897. 
Schalek:   Contribution  to  the  Histogenesis  of  Melanotic  Sarcoma  of  the  Skin.     Jijm. 

of  Cutan.  and  Genito-urinary  Diseases,  1900.  ' 

Steinnietz:  EinFall  v.  Melanosarkom  m.ausgedehnt.  Metastase.  I.-D.,  Freiburg,  31- 
Virchow:  Die  krankhaften  Geschwiilste,  ii.,  1864.  j 

Wagner;    19  Falle  von  Melanosarkom.     Miinch.  nied.  Woch.,  1887. 
Wallach-   Beitr.  z.  Lehre  vom  Melanosarkom.     Virch.  Arch.,  119  Bd.,  1890.      : 
Wiener.   Melanosarkom  d.  Rectimis.     Beitr.  v.  Ziegler,  xxv.,  1899.  • 

Williams;  Melanot isches  Uterussarkom.     Zeitschr.  f.  Heilk.,  xv.,  1894. 

{Chloroma.) 

Chiari.  Chlorom.     Zeitschr.  f.  Heilk..  iv.,  Prag,  1883.  HbJ 

Dock  and  Warthin:  Chloroma  with  Leukaemia.     Medical  News,  1904.  |^H 

Dressier:    Kin  Fall  v.  sogenanntem  Chlorom.     Virch.  Arch.,  35  Bd.,  1866.  :'    ^ 

Giimbel.    Das  Chlorom  u.  s.  Bez.  z.  Leukamie.     V.  A.,  171  Bd.,  1903.  _      [., 

Holing.  Z.  Kenntn.  d.  Chioroms.  Arb.  her.  v.  Baumgarten,  i.,  Braunschweig,  »^' 
Huber.    Feb.  d.  sog.  Chlorom.     Arch.  d.  Heilk.,  xix.,  1878. 


TlIK     inMTllF.IJAT.    TIMOKS.  WW) 

:iein  u.  Steinhaus:  Chlorom  (unterschoidc  cinen   lyiiiphooyt;in>ii.    oiiion    niyrlDcy- 

tart'ii  M.  oiiu'ii  .i:(Miiiscliten  Typiis).     C  f.  a.  Pii(li.,'.\v.,  I*)(M. 
.  Recklinghausen:   TajreM.  d.  ")S  Natiirforschorvcrs.  in  Strasshur;;,  ISS"). 
:isel:  Clil.ir.nu.     D.  A.  f.  klin.  Med..  72  Hd..  1901  (Lit.), 
'irchow:    Die  kraiikli.  (lesclnviilsto,  ii..  1S()4. 
Aildstein:   I'hlorolyiiiplioiit.     Vircli.  Arcli.,  91  Bd..  l.S.s:{. 

mold:    Zur  Lehre  v.  d.  Ban  u.  d.  l^ntwick.  d.  P.saintnoni(\     \ircli.  .\..  .")2  lid.,  IS7I. 
rnst;   T>ber  Psammonie.     Boitr.  v.  Ziejjler,  xi..  1S92. 
lOlgi:   Bail  u.  Kntwickeluna:  dos  Psaiiiinoni.s.     \'iicli.  .Vrcli.,  .')]  Bd..  ISTO. 
iBvi:    I'nters.  lilier  d.  Ban  ii.  d.l  jitsleli.   d.  ('oncrotioni'ii   in   Psamniomou   dor  Diini 
inatcr  cerebri  u.  d.  Kalkpkittclieii  d.  Araclmoidea  spinalis.      I. -I).,  Fn>il)iirfr,  1891. 
inser:   Verkalkte  Kndotlielioine.     Beitr.  v.  Bruns,  xxvi.,    19(K). 
etroni:   Sarcome  aiiiriolithiciue.     La  Roiiinaine  ined.,  1S9;^ 
;eudener:    Zur  Kenntniss  dcr  Sandgeschwiilste.     \'ircii.  .Vrcli.,  ."il  Bd..  1S7(). 
irchow:   Die  krankliaftcn  Gcschwiilste,  ii..  1SG4. 


(Siircoma  with  Hyaline  Fornidlion.s.) 


illroth:  Unter.suchungen  fiber  die  Entwickelung  der  Biiit<refas.se.  IS.^f). 
agonet:  Cylindrome  de  la  dure-mcre.     Arch,  de  ni<'HL  exp.,  iv.,  1,S92. 
Dembowsky:  Cylintlrom  der  Nasc.     Zeitschr.  L  Cliir.,  .T2  Bd.,  1.S91.    . 
vvetsky:   Zur  Cylindromfrafzie.     Viicli.  Arch..  09  Bd..  1S77. 
•anke:   Beitr.  zur  Geschwulstlehre.     Virch.  Arch.,  121  Bd.,   1890. 
•iedlander:  Geschwiilste  mit  hvaliner  Degeneration.     Virch.  Arch..  07  Bd..  1876. 
abavsch:   Krebs  d.  Ileunis.     Virch.  Arch.,  HI  B(L;  Cylindrome.     lb.,  122  Bd.,  1890. 
aier:   Beit  rag  zur  CyHiKb'onif  rage.     \'irch.  Arch.,  14  13d.,  1858. 
alassez:    Sur  les  cylindromes.     Arch,  de  phys.,  1883. 

archand:   I^ndothclioni  d.  An.  Ilighni.  m.   hyal.  Kugeln.      Beilr.  v.  Ziegler,  .\iii.,  1^*93. 
igenstecher:  Beitriige  zur  Geschwulstlehre.     Virch.  Arch.,  45  Bd.,  1869. 
littler:   Ueber  die  sog.  Cjdindrome,  Berlin,  1874. 
See  also  §§  114  and  115. 

2.  The  Epithelial  Tu.^ioks. 

(a)    General  Tiemarhs. 

^  117.  The  epithelial  tumors  are  new  f;i-owtlis,  in  tlio  formation  of 

viicli  b(»th  vascular  coiincctive  tissue  and  <'i)illn'lial  cells  -that  is.  cells 

\jiich  are  derived  from  either  superticial  or  j;landidar  eititiielinm — take 

lit.     The  distribution  of  epithelium  and  connective  tissue  follows  in 

p'nei-al  tlie  normal  arranj;ement  of  these  tissues,  tlie  connective  tis.sue 

her  forminj^  a  Imsement  structure  whose  sui-face  i.s  coveied  witli  epi- 

'liuiu  (.skin  and  mucous  membranes),  or  f«)rmint;  a  network  or  .stroma. 

the  meslies  of  which  the  epithelial  cells  are  disi)0.se(!  (},dands).     The 

itation  of  the  first-named  .structure  leads  to  the  formaiion  of  papillary 


312.-Paplllarv  epithelioma  or  l.litlivotic  wart  of  the  skin  (MOllor'.H  fliil.l.  hn'mntoxylln,  «H«ln).    «, 
Corlum  ;  h.  eiilurped  paplllar.v  l>o(ly ;  r,  laminated  homy  layt-r.     ■    ->. 


440 


TUMORS. 


new-growths ;  that  of  the  second,  to  the  formation  of  more  or  ?ss 
sharply  circumscribed  nodules  or  to  extensive  superficial  thicken  gs 
of  tissue. 

According  to  the  physical  characteristics  and  grouping  of  the  pi- 
thelial  cells,  as  well  as  the  clinical  behavior  of  these  tumors,  epithial 
new-growths  may  be  divided  into  two  groups;  one  group  including  he 
papillary  epitheliomata,  adenomata,  and  cystadenomata ;  the  cjer 
the  carcinomata  and  cystocarcinomata.  The  first  group  is  charactered 
clinically  by  the  benign  character  of  the  growths,  which  are  sharp! tir- 
cumscrihed  and  form  no  metastases.  The  second  group,  on  the  other  li_id, 
includes  the  malignant  new-growths,  which  grow  hy  iniiJtration  andive 
rise  to  metastases.  The  two  groups,  however,  are  not  sharply  sepai«d 
from  one  another,  as  papillary  epitheliomata  and  adenomata  may,  thngh 
changes  in  the  mode  of  reproduction  and  the  manner  of  spreading  o  he 
epithelial  cells,  become  changed  into  carcinomata. 

By  various  German  authors  all  epithelial  tumors  are  called  epitheliomata,  tlbe- 
nign  fomis  as  well  as  the  malignant.  The  French  apply  the  term  epithelioii  to 
carcinoma,  but  not  to  the  benign  papillary  epitheliomata,  adenomata,  and  adenocirto- 
mata.  The  extension  of  the  designation  epithelioma  to  all  epithelial  tumors  m'bc 
justified  from  the  scientific  side,  but  is  not  practical.  The  name  carcinoma  is  S(ini- 
versally  used  that  it  would  not  be  easily  given  up.  If  we  ajiply  the  term  epithelio  i  to 
both  carcinoma  and  adenoma,  we  are  deprived  of  anj- especial  designation  for  tl  be- 
nign epithelial  tumors,  and  we  are,  therefore,  forced  to  use  various  modifying  ms 
in  order  to  express  clearly  the  tumor-form  meant.  The  adenoma,  for  example, ''uld 
have  to  be  designated  as  epithelioma  adenoma tosimi  benignum. 

(?))  Papillary  Epithelioma,  Adenoma,  and  Cystadenoma. 

§  118.  A  papillary  epithelioma  is  a  new-growth  which  is  comijsed 
of  a  framework  of  connective-tissue  papilhe  covered  with  epithelial  |Us. 
In  structure  it  is  therefore  similar  to  the  papillne  of  the  skin;   bulthe 


W^^Jj^ 


Fig.  313— Senile  homy  wart  of  forehead,  from  a  woman  eighty-four  years  of  age  (alcohol,  hae 
lin,  eosin).  a.  Corium  ;  b,  epithelium ;  c,  atrophic  sebaceous  glands  with  development  of  horny  ep  : 
in  their  ducts  ;  c/,  hypertrophic  horny  layers;  e,  enlarffed  papilla?.    X  15. 


THE    KPITIIKLIAI.     TiMOKS. 

•111.-  Iii-liri-aiMl  < 


441 


tpapillfP  of  the  new  growth  are  as  a  iiih-  hi-hrr  ami  (.ftni  l.i; 
rtlie  epithelial  ('()\eriiig  thu'k«'i-. 

I  The  papillary  epithelioma  of  the  skin  occuis  in  tlu-  form  of  inirlif 
\protul»  nnici.s.  which  consist  of  slender  jjajiilhe  (Fig.  ."Uli)  covered  wilii 
icpithelinin,  the  sui)eilicial  hiyers  of  which  sln»\\  marked  <-ornilicalion 
iiclithi/otic  inirts  and  /loni//  inirt.s).  These  wails  may,  like  the  lleshy 
warts  (see  ;j  108),  ai)i)ear  dnring  childhood  ( iriiflii/olir  miii.s)  as  well  as  in 
K)k\  nine  (rerruca  senilis).  The  first -named  form  represents  a  local  mal- 
il'ormationof  the  skin  (Fig.  nV2)  ;  while  the  hist-named  isdn««  to  a  palho- 
ilogical  ])roliferation  and  cornitication  of  the  epilhelium  (  I'ig.  ;>i:>,  r,  d) 
jfollowed  by  an  outgrowth  of  the  ])ai)ilhe  at  the  i>eiiphery.  Anexees- 
Hive  cornitication  of  the  epitlieliuni  oAcr  hyixMliophic  jiapilla-,  gi\  ing 
jrise  to  cylindrical  or  conical  masses  of  liorny  cells  in  which  the  horny 
[layers  lie  at  riglit  angU^s  to  tlie  surface  of  the  skin,  leads  to 
Ition  of  a  ciitanroiis  horn  or  cornn  vntancinn  (  I'^igs.  i;il  and  !.'!."); 
,  Papillary  epitheliomata  of  the  mucous  membranes  o 
[in  the  foini  of  warty,  noduhir  foi-mations  (Fig.  314,  c,/),  or 
llong,  skMider,  papillary  exeres- 
•ences  (Fig.  315,  o),  which, 
pringing  from  a  narrow  base,  /,  ,  X 

u-e  often  re])eatedly  branched.  ^      '^ 

The  former  variety  is  found  es- 
pecially frequently  in  the  lar- 


the  forma- 


either 

that    of 


IG.  3U.— Papillary  epithelioma  of  tlifi  larynx,    n.  Epijrlnttis  ;  /),  oisilled  <rir..ii|  eartlla»f< 
latre  ;  </,  trachea  ;  c.  /,  papillary  prollfenitions.     Naiiinil  size. 

10.  31.5.— Papillary  epithelioma  of  the   iirinarv   hhnlijcr.    a.    K|»lihelli>iiia  :  /», 
thickened  bladder-wall.     Klve-slxtlw  uutural  size. 


C  thyroid  cartl- 
eiilurjfed  pn«Uite;    d. 


nx,  more  rarely  in  the  nose  and  urinary  bladder;  t  lie  lattermost  frequent - 

V  in  the  urinary  bhuUler  and  ])elvis  otthe  kidney,  vaginal  portion  ..f  the 

iterns,  and  more  rarely  in  the  ureter.s,  gall  bladder,  and  biliary  pas,s;ige.s. 

In  both  cases  the  excrescences  are  formed  of  slender,  connect  iveti.ssue 


442  TUMORS. 


vascular  papillfe  (Fig.  316)  which  contain  blood-vessels,  and  are  cover< 
by  a  thick  layer  of  epithelium.  The  character  of  the  epithelium  con 
sponds  in  geiaeral  to  that  of  the  part  in  which  the  growth  occurs,  b: 
papillomata  covered  with  stratified  squamous  cells  are  sometimes  seeui 
regions  which  normally  possess  cylindrical  epithelium  (nose,  trachea) : 

Papillary  epitheliomata  in  dilatatLon=cysts,  which  are  also  callli 
papillary  cystomata,  occur  most  frequently  in  cysts  of  the  ovary  ail 
in  cysts  of  tlie  ducts  of  the  mammary  gland,  more  rarely  in  atheroma 
(dermoids)  of  the  skin.  Within  the  cyst  are  formed  small,  warty  e- 
vations  or  caulitlower-like  tumors,  which  under  certain  conditions  mj 
fill  the  entire  cyst-cavity.  Their  structure  corresponds  to  that  of  1} 
similar  excrescences  in  papillary  adenocystomata  (see  §  120),  or  the  pa- 
illary  epitheliomata  of  the  skin  and  mucous  membranes.  , 

Papillary  epitheliomata  ot  the  surface  of  the  ovary  appear  in  forji 
similar  to  those  of  the  urinary  bladder,  but  are  lare.      Papillary  epitP. 


J 


Fig.  316.— Papillary  epithelioma  of  the  urinary  bladder  (alcohol,  hematoxylin,  eosin).    X  35. 

j 

liomata  of  the  cerebral  ventricles  take  their  rise  in  pait  from  the  t'» 
choroidete.  ' 

It  is  difficult  to  draw  a  sharp  line  between  papillary  epitheliomata  and  opr 
formatious.  In  particular  do  those  iiitlanmiatory  proliferations  of  the  skin  and  mn(|i8 
membranes — the  pointed  condylomata — which  tlevelop  especially  upon  tlie  extetil 
genitals  under  tiie  inlluence  of  chronic  irritations  (compare  Fig.  234),  so  closely  rcHi- 
ble  tlie  epitheliomata  tliat  their  inflammatory  origin  forms  the  only  point  of  di'r- 
ence.  If  the  connective-tissue  framework  of  the  papillary  outgrowths  is  devclij'd 
to  a  greater  extent  than  the  epithelium,  the  tumor  may  be  classed  with  the  papill  y 
fibromata,  and  it  becomes  a  question  of  individual  standpoint  as  to  which  desiumi '" 
siiall  be  enqiloyed.  Intermediate  forms  can  be  designated  as  papillary  f ibroepithe  ►" 
mata.  Finally,  the  benign  papillary  epitheliomata  may  jiass  over  into  carcinomiit 
either  through  the  growth  of  tlie  epithelium  at  the  base  of  the  papillte  into  the  UIl;^ 
lying  connective  tissue,  or  through  the  extension  of  the  proliferating  surface  epithelim 
upon  neighboring  organs  (as  in  the  case  of  the  papillary  epitheliomata  of  the  ovary; 

Among  the  epitheliomata  may  be  classed  those  formations  known  as  cholesteO- 
mata  or  pearl  tumors,  wliich  in  part  are  caused  by  inflammation,  and  in  part  re  e> 
sent  misplaced  embryonal  tissue.  The  most  striking  characteristic  of  the  cholesteat  iia 
is  the  formation  of  glistening  white  pearls,  which  consist  of  thin,  scale-like  epith'al 
cells  pressed  closely  together,  and  often  inclose  cholesterin.     These  tuiriors  are  f(  'd 


CIIOLESTKA'K  )M  A  .  443 

lost  frequpiitly  in  the  descending  uriniuy  ixissages.  tin-  cavities  of  the  middle  eur,  and 
a-  pirt  of  tlie  brain :  very  rarely  in  lliat  of  tin-  spinal  cord. 

PiitholDgieal  eornitieations,  willi  tlie  formation  of  glistening  white  scales  and 
earls,  occur  in  the  iiriiutn/  pussin/cx,  particularly  in  the  course  of  ciironic  intlaniuia- 
ons.  In  the  ti/inp<utir  can't i/,  manioid  autnim,  and  (\r/,riiiil  <iiiili(itn/  r<in<i/,  the  chole- 
ieatomatn  appear  as  yellowish-white  or  bluish  white  nodules,  varying  in  si/.«'  from  that 

!■  a  cherry-stone  to  that  of  an  vjiix,  and  jinscnting  an  onion-likt"  laminated  slruetun-. 
hrough  their  pressure  upon  the  neighboring  bone  they  may  cause  its  disjippearame. 
hey  arise  as  a  product  of  siiuainous  epithelium  which  has  penetrated  from  the  ex- 
ku'al  ear  through  openings  in  Ilie  ear-drum  into  ilje  cavities  of  tlie  midilie  i  :ir  and  has 
placed  the  cylindrical  cpitiieliuni,  and  under  especial  con<iitions  (chronic  intlamma- 
ins)  produces  the  formations  above  described.  It  is  probable  that  in  rare  cases  they 
ise  from  epidermoidal  cells  which  during  the  period  of  embryonic  development  liave 
Uuid  their  way  into  the  cavities  in  (luesiion. 

I  The  iniracnuiiul  cltohxtedtuninta  are  found  at  the  base  of  the  brain  (very  rarely  in  the 
>inal  canal),  iu  the  region  of  the  olfactory  lol)e,  tul)er  cinereum.  corjius  cai'osiim,  in 
e  choroid  jdexus,  in  the  pons,  medulla  olilongata,  and  cerebellum.  In  tiiese  regions 
e  cbolesteatomata  appear  on  the  surface  as  silk-like,  shining  nodules  of  varying  size 
liich  c.\tend  more  or  less  deeply  into  the  brain-substance.  The  nodules  are  single. 
It  cholesteatoma-masses  may  become  separated  from  the  ciiief  nodule  and  displaceil 
to  the  neighboring  tissue.  According  to  Ihiatnnn,  \l  is  always  i)ossible  to  demon- 
mte,  at  some  point,  a  connection  between  the  pia  and  the  chofesteatoma,  where  the 
ales  composing  the  cholesteatoma  take  their  origin  from  a  cell-layer  lying  ujion  the 
scular  connective  tissue,  the  cells  of  this  layer  throughout  bearing  the  ciiaracter  of 
idermoidal  cells.  The  cholesteatomata  of  the  pia  may  therefore  he  designated  as 
thelionutta  or  as  epiikrmoids  {Bf^Kf riiui) ;  and  their  origin  may  be  explained  by  the  as- 
inption  that  in  the  early  period  of  development  cpitiermal  germs  are  misplaci'd  into 
anlage  of  the  i>ia.  According  to  Bostrinn,  this  takes  place  in  the  time  between  the 
■sure  of  the  medullar)^  canal  and  the  separation  (by  a  process  of  constriction)  of  the 
?oudary  vesicle  of  the  fore-brain  from  the  fore-brain  or  the  'tween- brain,  and  thesepara- 
in  of  the  after-brain  vesicle  from  the  hind-brain  (fourth  to  lifth  week).  These 
idermoids  may  therefore  be  classed  with  the  teratoid  tumors  (see  Teratoma). 

Literature. 

{PapiUary  EpitheUoma. ) 

Ibarran-  Les  tumeurs  de  la  vessie,  Paris,  1892. 

^'irgengriin :  Verruca  dura  laryngis.     Virch.  Arch..  118  Bd.,  ls9'2. 

iellmann:  I'apilloma  durum  d.  Xaseu- u.  Stirnhohleiischleimh.     Arch.   f.   Larvng., 

;    vi..  is!»7  (Lit.). 

!:3pmann:    Warzengeschw.   d.   Respirationsschleimhiiuie.      Klin.     \'orir..    No.    :51"i, 

:     I.eil./ig.  is.ss. 

irael:  Epithelioma  folliculare  cutis.     Festschr.  d.  A.ssist.  f.  Virchow.  Berlin,  1HJ»1. 

larsteiner:  Paiiillome  u.  Krebse  d.  Blase.     Virch.  Arch..  130  Bd..  1S92. 

".ister:   llanil)lascngeschwiilste.     Samml.  klin.  Vortr.,  >.'o.  2(>T-(;s.  Leijizig,  IHHfi. 

:,inge:  Papilhmie  der  Mundhohle.     Deut.  Arch.  f.  klin.  Med.,  40  B<1. 

larchand;  Zur  Kenntniss  d.  Ovarientumoren,  Halle,  1ST9. 

lannenstiel:  Die   papillaren   Geschwulste  d.    Eicrstocks.     Arch.   f.    (Jyn.,  48  Bd., 

;      1  ><'.*.■>. 

£ietschka:  Ilistolotrie  des  Cornu  cutaneum.     Arch.  f.  Derm.,  42  Bd.,  1H9S. 

£ratz:  Die  C;esehwiilste  d.  Eierstocks,  Berlin,  1894. 

':chistowitsch:  Wachsthum  d.  Zottenpolypeu  d.  Ilarnblase.     Virdi.  Arch.,  ll.'iBd. 

Werner;  l}eitr.  z.  Kenntniss  d.  Papillome  d.  Kehlkoi)fs.  Heidelberg,  1894. 
Williams:    Papillomatous  Tumors  of  the  Ovary.     Johns  Hopkins  Hosp.    Bep.,   iii., 
I    liallimore,  1892. 
^iko:  Histologic  d.  Nasengeschwiilste.     Virch.  Anb.,  12s  IM.,  ls«i-.>. 

{('lioh'Htfatinna.  ) 

iieke:  Meningcale  Cholesteatome.     Virch.  Arch..  142  Bd..  is<».-,:  149  Bd..  1H97. 
liselia:  Cliolesteatomat.    Desquamation   im   Nierenbec  ken    b.    Tuberculose.      Vireii. 

.   -Vreh.,  99  Bd.,  1885. 
Ustrbm:  Die  pialen  Epidermoide,  Dermoide  u.  LijionK!  n.  dunilen  Dernioide.     Cbl 

;  t   allg.  Path.,  viii.,  1897  (Lit.). 

Ciari:  Cholesteatom(!  des  Hiickenmarks.     Prap.  med.  Woch..  1S8:5. 
Qieser:  Untersuch.  iiher  das  C'holesteatom.     Vircli.  Arch..  122  Bd  .  1890. 


444 


TUMORS. 


Gross:  Contrib.  ii  I'etude  des  tumeurs  perils,  Paris,  1885. 
Haug:  Das  Cholesteatom  der  Mittelohrraumo.     Cbl.  f.  allg.  Path.,  vi.,  1895  (Lit.). 
Nehrkorn:  ISfeningeale  Perlgescliwulst.     Beitr.  v.  Ziegler,  xxi.,  1891  (Lit.). 
Thomas:  Cholesteatomata  of  the  Brain.     Jour,  of  Med.  Res.,  1901  (Lit.). 
Virchow:  Ueber  Perlgeschwiilste.     Vircli.  Arch.,  8  Bd.,  18oo. 

§  119.  The  adenomata  are  usually  nodular  tumors  with  sharji' 
defiued  borders;  and  are  situated  within  glands,  or  in  the  skin  ormuccs 
membranes.  In  the  latter  situations  they  not  infrequently  appear  in  t!; 
form  of  polypi  elevated  above  the  surface.     They  may  occur  also  iu  t ; 


Fig.  317.— Adenoma  tubulare  (glandular  polyp)  of  the  intestine  (alcohol,  alum-carmine),  a,  Transv* 
section,  b,  longitudinal  section  of  gland-tubules ;  c,  stroma  rich  in  cells.    X  90.  | 

form  of  papillary  proliferations  (Fig.  241).  The  absence  of  any  teudei  y 
to  grow  by  infiltration  or  to  produce  metastases  stamps  these  growth^is 
benign  tumors. 


t 


Fig.  318.— Adenoma  tubulare  of  the  stomach  in  an  atrophic  mucosa  (formalin,  alcohol  haemato:  n< 
in),    a,  Mucosa;  h,  muscularis  mucosscB,  c,  submutobd,  (/,  muscularis;  e,  serosa;  /,  adenoma.   -  • 


4 


ADENOMA. 


445 


:  The  chief  characteristic  of  tlie  adcnoina.  is  thoformation  of  nrirf/Janth, 
nich  depart  more  oi-  less  I'roiii  tlie  typical  j;laiuls  of  the  aflV('t<'<ror<;an. 
jL'Cordin^^  to  their  structure  adcMioniata  may  be  classed  as  tubular  or 
iinous;  but  these  two  foi-ms  canuot  be  sharply  separated,  the  one  from 


319.— Adenoma  inammas  tubulare  (alcohol,  ahim-carmine).    a.  liranc 
cut  longitudinally;  h,  same,  cut  transversely;  c,  stn 

tb  other.     Through  the  formatiou  of  papillary  excresceuces  ou  the  inner 
\ills  of  the  glaud-spaces  there  is  formed  an  adenoma  papiJUfcrum. 
j  The  stroma  supporting  the  glands  consists  in  part  of  ])r»H'xisting  eon- 
I'ctive  tissue,  and  in  part  of  that  which  has  been  newly  formed. 

Adenomata  develop  either  i)i  normal  tissue,  malformrd  tissue,  in  tissues 
i^ich  have  been  altered  by  disease  (inliamed  mucous  nu'mbraiie,  cirrhotic 


it ''-'''"  ff^^'^r^  /'ir^l^^ 


%m 


^  380.— Adenoma  mammsc  alveolare  (alcohol,  aluiii-t,uiiiiini;>.    (i,  Tiimiiiai  aluuli;  //.  Klaii<l-<lucLs ;  r, 
connective-tissue  stroma.    X  27. 

Iter,  contracted  kidney,  ovaries  containing  scar  tissue),  or  from  remains 
ot'uial  structures.     The  new-formation  of  glands  is  dependent  upon  a  pio- 


446 


TUMORS. 


liferation  of  the  surface-epitbelinm  or  of  glandular  epithelium,  the  si 
or  this  process  being  similar  to  those  occurring  in  the  regeneratior 
normal  gland-tissue.  The  beginning  of  the  adenomatous  proliferai 
may  be  recognized  by  changes  in  tlie  form  and  staining  of  the  C(  s. 
This  is  i^articalarly  easy  in  the  case  of  the  stomach  and  intestine  in  wi  -h 
adenomatous  proliferations  so  often  develop  in  connection  with  infl;i. 
matory  and  ulcerative  processes.  The  change  of  the  gland-cells  ilto 
high  cylindrical  cells  staining  intensely  may  occur  at  the  same  timebr 
successively  in  a  number  of  glands  and  is  then  followed  by  cell-i:)rolifta- 
tion  and  new-formation  of  glands.  | 

The  cause  of  the  new-formation  of  gland-tissue  within  normal  orgis 
is  wholly  unknown.  Glandular  new-formations  developing  in  tisfies 
which  have  been  altered  by  inflammation,  and  which  lead  to  tumor- |ce 

growths,  ma;iiu 
t  h  e    begiui 


this  reason  jie 
o<len(n)i((Utca\ot 
he  sharph/  cli'^r' 
entiaicd  fronke- 
generative  (\.A 
hjipeypJaHtie 
li  fe  rati  0)1  H.      i 

T  u  b  u  I'  r 
adenomata  p- 
resent  the  ] 
common  for  ;of 
the  adenomja. 
They  occur  Ir- 
ticnlarly  in  lu- 
cous  inembrjes 
(Figs.  ;U7;.8, 
f)  provided  itli 
tubular  glands  (intestine,  uterus)  ;  but  are  found  also  in  such  glands  a.she 
breast  (Fig.  319),  liver,  ovary,  and  not  infrequently  in  the  kidrVs. 
They  are  characterized  by  the  formation  of  simple  and  bi-anched  giant 'u- 
bules  (Figs.  3f7,  a,  b;  318,  /;  and  319,  a,  b)  which  are  lined  by  simplelol- 
umnar  or  cubical  epithelium  and  form  nodular  tumors  varying  in  size  li)ni 
that  of  a  pea  to  that  of  an  apple  or  a  man's  fist,  or  rarely  even  lail^r. 
The  alveolar  adenomata  arise  from  glands  (mamma,  ovary,  thyijid, 
sebaceous  glands ) ;  and  are  characterized  by  the  formation  of  nuine'»U8 
terminal  bciTv-like  alveoli  (Fig.  320,  a),  as  well  as  gland-ducts  (ft).' 

Papillary  adenomata  (Fig."321,  a)  arise  through  the  formation  w:|iin 
the  liibulcs  of  ail  adenoma,  of  little  elevations  of  epithelium  into  ea(!of 
which  a  connective-tissue  papilla  grows.  The  local  epithelial  proler- 
ation  (c)  and  the  formation  of  papillte  (^7)  may  accompany  the  aty  ical 
gland-formation. 

The  stroma  of  an  adenoma  is  at  times  well  developed,  at  other  iaes 
but  slightly,  and  consequently  adenomata  may  be  divided  into  'w^ 
(mammary  gland)  and  soft  varieties  (kidney,  liver,  ovary,  testicle).  M 
especially  marked  development  of  the  connective  tissue  leads  to  th(or- 


Fig.  321. — Developins;  papillary  adenoma  of  the  kidiK  y.  (Alcohol, 
hEematoxylin,  picrofuchsin.)  (i,  b.  Fully  developed  tumor-tissue;  c,  d, 
early  stages  of  development  of  the  tumor.     X  150. 


ADKXOMA. 


447 


iiiitioii  of  fibro-adenomata  (w  jihroK.s  mh  iionKitn.  Siidi  rnrms  umir  most 
'it't|iuMitly  in  tli«'  in:niiiiiai-.\  yliind. 

If,  as  lia|)])tMis  not   iiifrciniciiIlN   in   llic   iiiaimnarx  ulaiid,  Ww  < iir<'- 

jve-tissuc  ])rolirt'rafi()ii  in  an  adenoma  is  ni>l  of  a  diliiis*' cliaiaclci',  liul 
Likes  i)lar('  paiticuhiily  uround  Die  caiialicMli  (see  Fij^.  L'r>()j,  llu"  lunior 
's  ordinarily  dt'sii^natod  as  a  fibroma  prricatialirufarc.  If,  as  \\\o  result 
f  more  marked  local  uroliferative  activity  on  the  ])art  of  tlic  <'onne«'tive 
issue  (Fiji'.  32l*,  <\  »/.  r\  an  iniirowth  of  ratlici-  i)roa(l  and  short  papilhe 


V_ 


-::vX^-;^v  ■^Xi';^iv.v./?: 


Fio.  322.— Fibroma  inlraranallculare  mamnia?  (flhro-adcnonia  papllllfeniin)  (alcohol,  aliin)-<-aniilnp). 
d[)«'nM>,  Interi-analicular  jfrowtli  of  llhrous  tissui-;  /»,  pi'titanalicular  iIsmu-  rlcli  in  (•••lis;  <■,  </.  r.  ruKlulur. 
'   iiriiimliciilar  nmnective-tissue  proliferations  cut  loniritiidinally ;  /,  iiiiia«iiiali>ular  pnillfi-nitlnnx  riil 

sviTbely.    X23. 

(j)  into  tlu'  },dand-spaces  takes  ]»lac(',  t  lie  result  in.u- t  iiiiior  iskiioun  as  a 
l»ronna  intracanaliculare.  According-  to  its  p-nesis  such  a  tumor  may 
i^)  l>e  appropriately  desiunated  a  fibro-adenoma  papilliferum. 

{(lemmntii  cannot  be  siiarply  (hilfrcntialcd  from  tunior-likc  jriamiiilar  liypt-rtro- 
fieson  the  one  liand,  and  caninoniata  on  tin;  oilier.     For  i-xainple,  in  tlic  lienljiij,' of 


•stinal  iilfcrs  tlie  rcfrcncralivc!  processes  in  tlie  tdands  may  tx- so  ailive  as  to  ;rivo 

to  polypoid  formations,  wliirli  may  eitlu-r  be  ealicd  f//<iiii'liit,ir/ii//,irtr,>ii/ii,M,,{l\w 

mrous  mvu\\>riiju'.  or  tifffii07niit(i,  iicnmWni:  to  tlie  individual  slandiioint.      Likewise, 

••rent  names  may  be  applied  to  the  glandnlar  polypi  which  occur  so  frequently  in 

uterus. 

The  ciirn'noinatous  nature  oi  a  new-i,M-owlli  resem!)linj,' an  adi-noma  (see  ^  TJl)  is 
gjierally  made  evident  bv  a  more  marked  ci)ith(lial  pmliferalion  and  by  its  intillrative 

Ic  of  growth.     There"aie,  however,  adenomata.  liaviiiL'  a  sin.L'l.'  layer  of  columnar 

s,  which  jrrow  bv  iiililtiation  (jtarticularly  in  the  intestine),  ami  thir.l>y  assmne  the 

meter  of  malii/nant  tumors.     'I'liey  should  aicordiuLdy  be  classeil  with 


th 


448 


TUMORS. 


mata,  and  must  be  designated  as  adenocarcinoma.  On  the  other  liand,  there  are  jo 
adenomata  with  marked  atypical  epithelial  proliferation  (mamma,  endometrium),  w.'jb 
— for  a  long  time  at  least— do  not  show  any  malignant  characteristics. 


Literature. 

(Adenoma.) 


55  Bd.,  1895  (Lit.).  | 

Stuttgart,  1,6 


Barlow:  Adenomata  scbacea.     Deut.  Arch.  f.  klin.  Med. 

Beneke:  Leberadenom.     Beitr.  v.  Ziegler,  ix.,  1891. 

Billroth:  Tumoren  der  Brustdriiseu.     Handb.  d.  Frauenkraukh 

Bock:  Ueber  ein  Adenom  der  Talgdrusen,  Berlin,  1890. 

Bonome:  Coutr.  alio  studio  degli  adenomi  del  legato.     Arch,  per  le  Sc.  Med,,  ;t, 

1889.  ; 

Brinaud:  Du  polyadenome  gastrique.     Arch.  gen.  de  med.,  1885.  j 

Eberth:  Das  Adenom  der  Leber.     Virch.  Arch.,  43  Bd.,  1868. 

Hauser:     Polyposis  iutestinalis  adenomatosa.     Deut.   Arch.    f.   klin.  Med.,  55  1, 

1895;  Priniare  z.  Geschwulstbildung  filhrende  Epithelerkrankuug.     B.  v.  Ziej'-r 

xxxiii  ,  1903. 
Hofifmann:  Adenom  der  Leber.     Virch.  Arch.,  39  Bd.,  1867. 
Kelsch.  et  Kiener:  Contrib.  3, 1'hist.  de  I'adenome  du  foie.     Arch,  de  phys.,  1876. i 
Iianghans:  Ein  Drlisenpolyp  des Ileums.     Virch.  Arch.,  38  Bd.,  1867.  ' 

Leser:  Beitr.  z.  path.  An.  d.  Geschwlilste  d.  Brustdriiseu.    Beitr.  v.  Ziegler,  ii.,l!;8. 
Lubarsch:  Adenome.     Ergebn.  d.  allg.  Path.,  vii.,  1903.  j 

Menetrier:  Des  polyadenomes  gastriques.     Arch,  de  phys. ,  i.,  1888.  ! 

Nissen:  Leberadenom  bei  Cirrhose.     Inaug. -Diss.,  Freiburg,  1895.  ; 

V.  Noorden:  Das  verkalkte  Epitheliom.     Beitr.  v.  Bruns,  1888.  ! 

V.  Becklinghausen:  Die  Adenomyome  u.  Cystadenome  d.  Uterus  u.  d.  Tube,  Bun, 

1896.  : 

Bicker:  Geschwlilste  der  Niere.     Cbl.  f.  allg.  Path.,  viii,  1897. 

Rovighi:  Adenoma  racemoso  del  fegato.     Arch,  per  le  Sc.  Med.,  vii.,  1883.  j 

Simmonds:  Die  knot.  Hyperplasie  u.  d.  Adenom  d.  Leber.     Arch.   f.  klin.  Me(;,34 

Bd  ,   1884.  : 

Steudener.  Adenom  der  Brustdriisen.     Virch.  Arch.,  43  Bd.,  1868,  ] 

Weichselbaum  u.  Greenish.:  Adenom  der  Niere.     Wiener  med.  Jahrb.,  1883.  I 

See  also  g§  118  and  120.  j 

§  120.  A  cystadenoma  or  adenocystoma  is  an  adenoma  whose  gV^- 
spaces  have  undergone  ci/sHc  dilatation  through  the  accumulation  of  secret  ps. 

Such  tumors  are  usually  ^m- 
posed  of  numerous  cysts,  nd 
are,  therefore,  desiguated  as 
multilocular  cystomata.  |^c- 
cording  to  the  character  ol:he 
cyst- wall  there  may  be  di.in- 
gulshed  a  smooth-ioalled  or  s  j^pZe 
cptoma  (cystoma  simplex),  •'  a 
papuliferous  cystoma  (cystomalap- 
illiferum).  I 

Small  amounts  of    seer  ion 
are  often  seen  in  the  ordlary 
adenomata  (Fig.  317),  aucjthe 
spaces  of  both  simple  and  (;ap- 
illary   adenomata   are   ofte'  so 
wide   (Figs.    310,  a;    322)lhat 
they  at  once  attract  the  e^j  on 
cross-section  of  the  growth'  lu 
cystadenomata  such  cyst-fcma- 
tion  is  the  predominating  mat- 
ure. ; 
The  early  stages  of  the  cysts  are  represented  by  gland-tuhules  of  Hy- 
ing shape  (Figs.    323  and  324,  ?>),   which  lie  in  a  more  or  less  ijWy 
developed  connective-tissue  stroma.     Through  the  accumulation  of  i  ere- 


Fig.  32.3.— Section  of  a  cT.stadenoma  ovarii  papilliferum 
(Muller's  tluid,  h»mato.\ylin).     X  40. 


CVSTAl)i:\(  )M  \., 


449 


tioii  thos«'  tulmk'S  IxH-oiue  ^r:i(lii;illy  dilated  so  llial  miiiicn»iis  small  cysts 
arise  (Fig.  ."•_'">).  or  else  botli  largo  and  snialloysts  (I'Mgs.  .'iL*(i-.{;;(»)';ire 


* .  ","7  ■*r^'i3 


p^^^Pp^^^  ■; 


V  • --■   ■"S^"Cv^^3^^^ft'--^^^?'^^*~ "     ' '    '  '  ■  ■•'^ ■ ' ' 


t  "J^^r^'iS^^:.  ;^^!?^'';  ■ 


fIG.X;4.— Adenocystoma  of  the  bile-p:is>iiKis  in  ilir  ilrsi  >iaL'.  -  ..f  (U'velupiaent  (alcolii.l.  liii-iii!it<ixylln), 
(1.  I.iver  tissue;  /«,  adenoma  tissue  in  tin-  iMTiiioiial  cuuiieetive  tissue.     X  90. 

onued.     Often  tlie  lelatioiisliij)  is  sueli  that  the  tniiior  may  e<nisist  of  a 
e\v  large  cysts  (Fig.   329)  in  Mhose  walls  smaller  cysts  occm-;  or  there 


""-m 


hi...  i.'.,.  KIU.  3W. 

Fio.  ;ai.— Sfttlon  of  a  |)ortlon  of  a  multlliNular  adeiuK-y.stoiua  of  the  ovar>'-    U.ilui-.tl  tilMUit  one-»lxth. 
Fio.  :Wi.— Section  through  an  adentxystoina  of  the  U-slls  of  a  four-year-old  Jioy.    Natural  hIw. 


450 


TUMORS. 


:^f 


Fig.  327.— Multilin  ,,,<i.   ^,ili  .uH  \siwiii,i  i)f  tlie  liver,  seen  in  section,     a.  Liver  parenchyma;  h,i\a. 
btanoiis  margin  of  the  left,  loliu;  c,  t/,  laige  cysts;  c,  group  of  smaller  cysts,  separated  from  each 
only  by  connective  tiisue;  f,  portal  vein;  y,  hepatic  artery.    Two-thirds  natural  size. 


Fifi.  328,— Cystoma  of  thp  kidney,  cut  transversely.    Eleven-fourteenths  natural  size. 


CYSTADKNOMA. 


451 


nay  be  found,  by  tlio  side  of  larf>o  cysts  (Fi^.  327,  <•),  lun-lions  of  i  issue, 
vliicli  contain  only  small  cysts  (c)  or  even  api>car  s(»li(i-  tliiil  is,  cunslsi 
u'j:  of  a  tissue  the  ulandsof  which  are  not  dilated. 


!:^^«<r„..:; 


Fig.  329.— Adenocystoma  ovarii  partim  siniiili-x.  iiMitim  iia|iillif.rMiii.  </.  Smootli-wulUHl  cysts:  /».  soft 
pillary  prowth  roverfil  with  simple,  miiciis-forming  cyliiulrirul  epltlieliuni.  (Metastjittc  iiixltilcs  wen- 
•st'Ut  in  the  peritoneum.)    Reduced  one-third. 

All  the  different  varieties  of  cystomata  may  dc\<'loi»  in  the  oxaries 
='igs.  325  aud  329),  testicles  (Fig.  326),  liver  (  i-'i-s.  ;!-J4  and  ;V_'7  i. 
dueys  (Fig.  328),  and  the  mammary  glands. 


0. 330.— Portion  of  a  papillary  adenof;ystoma  of  the  ovary,  .•"•en  In  s«'<lloii.    i  Iiruwn  frmn  u  »iM'<liiiei» 
hardened  in  chromic  acid.)    Kour-UfthM  Dulural  size 


452  TUMORS. 


lu  the  ovaries  cystomata  not  infrequently  develop  coincidenth  on 
both  sides,  and  may  be  associated  with  dermoid  formations.  Adencijs- 
tomata  of  the  testicles  not  infrequently  inclose  within  their  stroma  Dci 
of  cartilaii-e  or  other  tissue,  so  that  such  growths  should  be  classed  th 
the  icratomafa  (^  128). 

The  cpHluiial  I hiiiif/ of  cystomata  is  usually  composed  of  simple  eo  ul- 
nar cells,  but  may  be  a  ciliated,  cubical,  or  liattened  epithelium. 

The  cyst-contents  usually  consist  of  a  clear,  often  distinctly  ropy  fid, 
which  contains  a  mucin-like  substance  (pseudoinucin,  see  §  59).  his 
substance  is  a  product  of  the  epithelial  lining  in  which  goblet- cells, ire 
often  found  (Fig.  331,  c).  Is'ot  infrequently  the  fluid  alsocontaiusAiit- 
ish  flakes,  the  products  of  cells  which  have  uudergone  fatty  degeneram ; 
or  it  may  be  more  or  less  cloudy  or  reddish  or  brownish  from  previ(isly 
occurring  hiEmorrhages.  An  abundant  secretion  in  many  cysts  niaykil 
to  the  formation  of  tumors  of  enormous  size;  in  the  ovary,  for  exarile, 
they  may  reach  a  weight  of  from  ten  to  twelve  kilograms  or  more,    j 

The  papillary  adenocystomata  constitute  a  common  variety  of  a('ao- 
cystoma.  Tliey  are  characterized  by  the  fact  that  sooner  or.  later  pjjil- 
lary  excrescences  develop  in  the  glands  whicli  have  undergone  c;?ti(' 
degeneration.  ; 

In  the  adenocystomata  of  the  ovary  these  excrescences  are  us  Lily 
slender  and  delicate,  forming  villous-like  outgrowths  (Fig.  330)  or  (iili- 


%.^^-.     /, 


^mr 


>.-,J^ 


Fig  5.J1  —Cystoma  papi  Mferinn  ov  ini  (Miillers  fluid  Inematoxvlin  eosin)  (i  ^Xx  mi  \\ith  .pl"^'• 
^,  glaml  tiibuU  witli  smill  pipilli  <  huh  t>hndii(  il  tpithehum  d  muciib  contdininf^  tells  w!ln""* 
cyst-spaci's.    X  150.  | 

flower  elevations,  which  may  fill  up  a  larger  or  smaller  i)art  of  thejysts. 
IVriuute  i^apillary  elevations,  extending  over  an  extensive  area  i  the 
inner  surface  of  the  cyst-wall,  may  give  to  the  latter  a  velvety  apear- 


I 


I'APIM.  Ain      CVSIADKNOM  A. 


4o3 


jince  similar  to  that  of  a  luiu-ous  iiu'iiilnaiir.      If  (inM'x<'irs«'«'nc«'s  drvrlup 
jiii  eysti?  of  small  si/A',  tiu'y  may  till  llicsc,  and  llic  tis,siu'  may  liinchy  lake 
bn  the  apiH'arance  of  a  tU'iisi>,  non-cyst ic,  nu dnllaiy  tnmoi!  Hmnuli  fium 
ihe  cut  surface  more  or  less  mucus  can  usually  Im-  uhtainrd. 
1      Larjrer  i>ai)illiv  are  always  more  or  less  branclicd  (  Kij;.  .'>.{I  •.  and  cui 
kist  of  a  cellular  stroma  (a),  whose  surface  is  usually  covered  witii  tall 


Fig.  XC— Papillary  adenocystoma  of  the  ovary  with  myxomatous  dejieiuTaiiim  <>f  thi-  oonniHtlve  tissue 
r  the  papilUe  (Miiller's  fluid.  ha?mato.\vlin).  «,  Fibrous  stroma;  h,  papilla'  whirh  hiivc  undenfone 
yxomatous  '-hange;  c,  epithelium.     X  Ht. 


olummir  cells  (/•)  of  the  character  of  ^n>hlc{ -cells.  The  cnnl«'iils  of  liic 
y.sts  consist  of  ropy  mucus  (//)  minjiled  with  more  or  less  uumei«ms 
esquamated  cells  which  have  undergone  mucous  depMieration.  or  the 
emains  of  such  cells.  In  rare  cases  the  connective  tissue  of  tiic  pajfilla- 
lay  undergo  a  mucous  degeneration  (Fig.  .'^•>-.  <>,  /'),  ami  may  swell  to  a 
larked  degree,  and  finally  become  changed  into  myxonialoiis  spheres 
Dvered  externally  with  ei)itheliuni. 

Adenocystomata  of  the  li\-ei',  testicles,  and  kidneys  usually  form    no 

apilhe,  or  at  most  very  small  ones.      In  the  pajjillaix  adenoe\.sl ala  of 

le  mammary  gland  the  exciescences  are  usually  l»i-oa<l  and  plump  ( l"'ig. 
33), as  is  the  ca.se  with  tho.se  of  the  ])apillary  adenomata  (Fig.  '■'t'-l). 
Lccordingly,  <)n  the  cross-section  of  such  tumois  the  cyst -spaces  are  found 
)  l)e  filled' with  ])olypoid  i)roliferations  of  various  forms  (Fig.  '.V.V.\), 
hich.are  often  tlattened  through  mutual  jncssure.  and  give  to  tin*  .siir- 
ice  of  such  a  cross-section  a  laniinaled  ap|>earance. 

Since  in  these  tumors  the  connect  i\e-t  issiK 
le  epithelial,  the.s«'  growths  aiv  often  clas> 
motH,  and  designate<|,  accoiding  to  the  character 
le.    as   ci/sfofi/nonut,    ci/stonii/roiiKf,    or    ci/stn.stnrt)iin(. 
iniclure  of"  leaf-like    layeis  they   ha\c  iecei\ei|ll 

The  papWanj  admori/.sfomdfd   show   a    nrtuiu   ninlif/iHinri/,   even   when 
lepapilhe  are  covered  with  a  simple  epithelium  ( s«'e  cystocarcinoma). 


'ienieiits  ]i|-e<lominate  oxer 
I  with  the  cninirctin  tis'-ttr 
if  the  connect  i\e  lis- 
\\hen    showing  a 

nie    ot'    sdiriiniil 


454 


TUMORS. 


This  is  shown  iu  the  first  i^lace,  in  the  fact  that  the  papillary  prolif( 
atious  may  break  through  the  cyst-wall,  iu  the  case  of  such  tumors  " 
both  the  ovary  and  mammary  gland,  and  iu  the  latter  situation  they  m  • 


Fig.  333.— Papillary  cystoma  or  intracanalicular  papillary  fibroma  of  the  breast,  laid  open  by  a  Ion; 
tudinal  incision.    One-balf  natural  size. 

also  break  through  the  skin.  Papillary  ovarian  cystomata  (Fig.  329.1) 
may  iu  this  way  give  rise  to  metastases  iu  the  peritoneal  cavity,  ;jd 
these  in  turn  display  the  characteristics  of  papillary  epitheliomata.     '■ 


The  adenocystomata  represent  a  variety  of  tumor  wliich  possesses  no  sharply  def.d 
limits;  for  example,  papillary  cystomata  may  arise  from  the  development  of  papilT 
excrescences  iu  dilatation-cysts  which  are  formed  from  pre-existing  glands  (see  §  h)- 
Further,  malformations  of  organs— for  example,  of  the  kidneys  (Fi^.  328)— may  iKito 
tlie  formation  of  nuillilocular  cystomata,  the  cystic  dilatation  affecting  not  only  .le 
urinary  tubules,  but  also  Midler's  capsules.  That  teratomata  may  appear  in  the  Jim 
of  adenocystomata  has  already  been  mentioned  in  the  text.  Finally,  a  transition  IJB 
cystadenoma  to  cystocarciuoma  may  also  take  place.  ! 


Literature.  , 

(Adenoci/.stoma.)  I 

Bard  et  Lemoine:  La  maladie  kystique  essent.  des  organes  glandulaires.     Arch.  n. 

de  med.,  1890. 
Baumgarten:  Ovarialkystom  mit  Metastaseu.     Virch.  Arch.,  97  Bd.,  1884. 
Billroth:  Handb.  d.  Fniuciikrankheiten,  iii.,  Stuttgart,  188(5. 

Bottcher:  Entwickelung  niullilocularer  Eier.stockscysten.     Virch.  Arch.,  49  Bd.,  :  0. 
Brissaud:  Maladies  kystiiiues  dc  la  mamelle.     Arch,  de  phys.,  iii..  1884.  ^; 

Brodowski:  Alit  Flimmerepithel  ausgekleidete  Ovarialcysten.     Virch.  Arch.,  67  i. 

187(). 


I 


CARCINOMA     AM)    (  A  S  lex  '  A  iv'<   1  \(  »\l  \  .  1.')') 

.Burckhardt:  Genese  d.  nuiltilocul.  Ovariak-ysti'ii.     Vircli.  Arcli..  144  IJd.,  1^90. 

,Coblenz:    Kyslome  dw  Oviirini.     Zcitsclir. "  f.  (}cl).    ti.    (}yii..   vii.,    ISM'J;  (Jciicsc   ii. 

;        Kiitwukclmiir  von  Kystomcn.     Viicli.  An-li.,  S4  IM..  issi. 

(Dmochowski  u.  Janowski:  TotaU- cystischc  Knt.irliiiiir  d.  Ltlirr.      I5tiir.  v.  ZiciMcr, 

I        xvi..  1S»14. 

Flaischlen:  3IuUiloculair  FliinnuTopithclkvsloinc  dtr  Ovaricii.     Zcitsclir     f    (Jvii 

vi..   ISSl. 
Goebel:   Kicfcriiiniorcn  v.  Zaimsystom  uvis^dieiid.     C'ltl.  f,  alljr.  Patli..  1S!)7  (Fiit.). 
Hess:  I'ltior  cine  siibciitaiic  Fliiiinicrcystc.     Bcitr.  v.  Zici^lcr,  viii.,  1N<H». 
V.  Hippel:  Midtiplcs  Cyslt'iiadciuuu  dcr  Gallciiiciingc.      Vircli.  Arch.,  l'.':i  15d,.  isill. 
Israel:  Kpiiiiclioma  follicularc  cutis.     Fcstsciir.  <i.  Assist,  f.  Vircliow.  Hcriin,  isitl. 
|V.  Kahlden :  Gciuso  dcr  imiltiloc.   Cystcnnicn"  u.  d.  ("ystoiilcbcr.     Hcilr.   v.  Zicijlcr, 

xiii.,  lt>93;  Coucen.  Adcuom    bcidcr  JSieivu.     lb.,  xv.,  1894;  tliitsU-li.  d.  Ovuiiiil- 
I        cystcn.     lb.  x.\vii.  1900. 

Kocher:  Die  Kianiciu-itcn  dcs  lindens,  Stnttirarl,  1S82. 
Labbe  ct  Coyna:  Traite  dcs  tuin.  bcnigncs  du  scin,  ISTfi. 
Leser:  I'xitr.  z.  patbol.  Anatomic  d.  Geschwiiisto  d.  Bnisldiuscn.     UrUr.  v.  Zicirlcr, 

Malassez:  Maladies  kystiques  dti  Icsticido.     Arcli.  dc  phys.,  1875. 

Marchand:  licitr.  z.  Kenntiiiss  dcr  Ovarialtuinorcn.  1879.. 

Michalowicz :   I)c<;;encrcsccncc  l\ystiquc  dcs  reins  ct  du  foic,  Paris,  1877. 

Monod  el  Terillon:  Traite  dcs  iiialadics  du  testicule,  Paris,  1889. 

Nagel:  (icncse  dcr  epitiiclialen  Eierstocivsireschwiilsfe.     Arcii.  f.  Cyu.;  ;!:!]'.(1..  1M88. 

Nauwerck  u.  Hufschmid:  Ueb.  d.  multilocui.  Kystonie  d.  Nierc. '    llcitr.  v.  Zieglor, 

\ii..  1S9-2. 
Dlshausen:  Die  Krankheiten  d.   Ovarien.     Ilandb.  d.  Frauenkrankheiten,   ii.,  Stutt- 

irart.  iss6. 
Pfannenstiel :  Die  Pseudoniucine  dcr  cvstischeu  Ovarialsresciiwiilste.     Anli.  f.  Gvn., 

:}S  15.1..  1S90;  Xeul)ilduiio;eu  dcs  EieVstocks.     Ilandb.'d.  Gvniik.  v.  Vcit.  iii.,  1898. 
Ruge:  Papillifornies  Atheroni.     Vircli.  Arch.,  i;](;i5d.,  1894. 

5abourin:  I)eu:enerescence  kystique  du  I'oie  et  dcs  reins.     Arch,  de  phys.,  x..  1882. 
Basse:  (ysten  u.  cystische  Tunioren  der  ^lannna.     hanjL'^enbcck's  Arcii.,  54  IJd.,  1S97. 
Schmidt:  Cystosarkoin  der  Mamma.     Arch.  f.  Gyn.,  xxii.,  1884. 

ie  Sinety  et  Malassez:  Sur  la  structure,  roriirine  et  ic  devcloppement  des  kvstes  de 
;       Tovaire.     Arch,  de  phys.,  1878,  1879,  1880,1881. 
istratz-.  Die  Geschwiilste  des  Eier.stocks,  Berlin,  1894. 

Cerburgh:  I'eber  Leber- u.  Nierencysten.     luaug.-Diss.,  Freiburg,  Leiden.  1891. 
^  Velits:  Genese  der  Flimmerepithel-Kystome  des  Eierstocks.     Zeilschr.    1'.    (Jcb., 

xvii..  1891. 
Sdppritz:  Multiloculiire  Kiemengangscysten.     Bcitr.  v.  Bruns,  xii.,  1894. 
I      See  also  ii  119. 

((■)  Carcinoma  and  <'y.sf(>ca)cin(>ni((. 

\  iL'l.  Tlio  carcinomata  nvQ  nialif/nant  rpH/ir/ia/  hininrs  cliarMclrri/cd 
}j  infiltrativf  fftoutJi  and  Ww  Jhmiatlon  of  inrfastoscK. 
They  develop: 

(1)  111  the  skin,  imieous  ineiii])raii('s  and  in  glands,  all  <d'  wliirli  ap- 
peared to  be  iionnal,  Ix'foie  the  de\  «'h»i>nient  (d"  the  careinunia. 

(2)  In  the  skin,  niueoiis  ineiiilnaiies,  and  in  ^land.s,  wliicii  lia\«' 
Iready  siitlered  eliany-es  iMdoiv  thr  de\  (dopincnt  id"  the  carcinoina. 

(8)  In  already  e.xistinj;-  pai)inaiy  epilhrlioinata,  adenomata  and  ade- 
ocystoinuta. 

(4)  From  the  remains  of  f(elal  epitliclial  st  iii.t  mv.s  and  rmm  .•pillif- 
al  tis.sues  M-liich  have  l»een  niis])laeed  tliioti.uh  dlst  nrhaners  ni  d.-v  <  |..p- 
lent,  and  liave  already  developed  into  jiatholouical  foriiiatiuns. 

(5)  From  the  eiiillwiial  1i.ssiu-s  «d'  the  (•li..ii<.iiic  \  illi  and  piaccnia. 
The  most   essential  ehaiaclciist  ic -d'  tlx-  drv  .-I.. pnimt  nf  :i  caiviiM.nm 

that  jncscnted  by  atypical  proliferations  of  epithebum  which  sooner 
r  later  penetrate  into  the  tissue  bordering  upon  the  affected  Kl^'id** 
r  surface=epithebum.  Tliis  ph<num.n(Mi  is  usually  acc.mpanird  b\  a 
roliferation  of  connective  tissue  ;  Imt   this  is  imi   altsnlnidy  c.Nsmtial 


456  TUMORS. 

to  the  development  of  a  carcinoma.  The  tissue  invaded  by  the  epitheli 
proliferation — M-hether  glandular  tissue,  muscle,  bone,  etc. — is  soou 
or  later  destroyed  by  the  growth,  although  within  the  stroma  of  the  ca 
cinoma  there  may  occur  a  new-formation  of  other  tissue  than  counecti' 
tissue,  as,  for  example,  bone. 

The  cause  of  the  atypical  growth  of  epithelium  is  not  known  wi ' 
certainty;  it  can  only  be  said  that  certain  conditions  favor  such  growt] 
Thus,  for  example,  ohl  ^^//(^  predisposes  to  the  develoi)ment  of  carcinoma! 
of  the  skin,  inasmuch  as  in  this  period  of  life  the  connective  tissue 
the  skin  undergoes  a  certain  amount  of  atrophy  and  becomes  looser  ' 
structure,  while  the  epithelium,  at  least  in  part,  continues  to  inc^ea^^ 
and  under  certain  conditions  shows  here  and  there  distinct  evidences  i 
increased  activity  (formation  of  coarser  hairs  upon  the  nasal  septui' 
lobes  of  the  ears,  and  in  the  eyebrows).  Likewise  carcinomata  of  t| 
mucous  membranes  and  the  glands  usually  appear  in  the  later  years 
life,  although  they  may  occur  earlier  in  life,  even  in  childhood.  j 

A  further  2}redisposition  to  the  deveJopmrnt  of  carcinoma  is  found  : 
regenercdive  processes  following  the  destruction  of  surface  epithelium  aij. 
glandular  tissue.  These  occur  most  frequently  in  old  InHammidorn pri\ 
esses  th^t  have  led  to  tissue-destruction  and  new-formations  of  tissi; 
particularly  in  the  mucous  membrane  of  the  intestinal  tract,  gall-bladdc 
and  uterus,  and  also  in  glands  and  in  the  skiu.  In  the  stomach  the  rou  ji 
ulcer  (  Ulcus  ex  digestione)  may  form  the  starting-point  of  a  cancer,  i 
the  first  place  the  regenerative  proliferation  f<;»llowing  the  tissne-iujuf 
may  form  the  basis  for  an  atypical  malignant  i>roliferation.  In  additih 
an  important  role  is  played  by  the  snaring-off  and  mi.spJacoitent  of  eplthe^ 
cells  into  the  neighboring  altered  connective  tissue,  a  phenomenon  of  freqiifi: 
occurrence  in  the  healing  of  ulcers,  the  growth  of  epithelium  over  gn- 
ulation-tissue,  and  in  tuberculosis,  and  other  chronic  infective  grauu|- 
mata,  both  iu  the  mucous  membranes  and  skin  and  also  in  glands.        '. 

All  these  predisposing  factors  do  not  constitute  the  unique  cause  -f 
the  development  of  a  carcinoma.  They  may  exist  for  a  long  time  wi  - 
out  giving  rise  to  a  cancer.  It  appears  that  something  else  must  ? 
added  to  cause  the  unlimited  atypical  proliferation  of  epithelium,  a;l 
what  this  something  is  is  at  present  unknown.  "Whether  this  causes 
to  be  found  in  a  bioplastic  stimulus  comparable  to  that  of  fertilizat -i 
or  in  chemical  influences  stimulating  the  cells  to  increased  proliferat  i 
or  iu  the  removal  of  the  influences  that  inhibit  and  regulate  proliferat , J 
caunot  be  stated  at  the  present  time.  ' 

In  recent  years  the  opinion  has  been  many  times  advanced  and  mn*.- 
tained  that  parasites  cause  carcinomatous  and  sarcomatous  prolil;"- 
atious.  But  the  majority  of  the  appearances  which  have  been  descrilil 
as  parasites  (as  protozoa,  especially  sporozoa,  and  as  yeast-fungi)  he 
not  been  parasites  at  all,  but  degenerated  nuclei  and  nuclear  divisii- 
figures,  or  leucocytes  inclosed  within  tumor-cells,  or  degeneration-pni- 
ucts  of  such,  or  products  of  cell-protoplasm,  particularly  keratohyj.B 
and  colloid,  or  epithelial  hyalin  and  mucin.  In  the  few  cases  in  wb.Ii 
true  parasites  were  present  in  the  tissues,  this  occurrence  could  very  "siU 
have  been  a  secondary  infection,  Mdiich  in  no  way  could  be  regarded  :  a 
cause  of  the  development  of  the  tumor.  In  not  a  single  case  has  it  /'« 
proved  beyond  all  doubt  that  parasites  have  been  the  cause  of  either  carcimd 
or  sarcoma. 

Certain  portions  of  the  intestinal  tract — the  rectum,  the  flexurei-'f 
the   colon,    the   pylorus   and   cardia   of  the    stomach,    the   oesopha^?, 


(A  K(   I  NOMA.  457 

liaryii.x,  tongue,  and  <iunis- arc  lavorih'  s.ats  fur  the  (lfVi'l()i)iiuMi(  of 
infer.  I'aiu-er  may  develop  in  any  i)oiti..u  (.ftlu'  skin,  bnl 'iloeenis 
lore  freqnently  on  the  lips  and  nose  than  on  the  nMnaininj;  i>ortions  of 
le  faee.  or  on  the  extremities,  and  on  tliesc  a.uain  more  liciincntly  than 
11  the  trunk.  Of  the  sexual  apparalusthe  ]>aits  most  eoninioniy  ail'etled 
'•e  the  mammary  ^land  and  eervieal  i)orlion  of  tlie  utrrus;  less  fre- 
'iiently,  thousih  relatively  often,  the  ovaiy,  testicles,  body  of  the  ulerns, 
iilva,  vayina.  and  ])enis.  The  liver,  kidneys,  hladfler,  trachea,  hronchi. 
nijjs  and  i)ancreas  occupy  a  middle  .uronnd;  while  the  larynx  and 
dl-bladdcr  are,  on  the  otlu^r  hand,  moi-e  fre(|nen11y  alVeclcd. 

Cancer  usually  develoi>s  in  the  form  <tf  muhiJrs,  trhirh  mr  imt  .slinijtf;/ 
fferentinted  from  the  neighl)orin<i'  tissues;  on  tin'  mucous  nieinliranes 
.ey  are  not  infrequently  elevated  above  tlie  surface  in  the  form  of 
onge-Iikr,  ov  poJi/jxiid.  or  papil/dri/  f/roirt/is.  From  the  point  of  orij^iu 
ley  spread  by  an  infiltrative  growth  of  the  ei)ithelial  i)rolifeiati(.n.s, 
1"  which  cither  the  nodules  iiu-rease  in  sizeortliere  are  foinied  dilfns«' 
sperticial  thickenings,  as  in  the  case  of  the  intestinal  wall,  'i'he  ovaries, 
(sticles,  uterus,  kidneys,  etc.,  may  be  i)artly  (u- wholly  transfoinied  into 
dreinomatous  tissue.  Often  the  boundaries  of  the  oij^mu  ori;;inally 
:}t\H'ted  are  overstepped,  and  the  epithelial  infiltration  cxt»Mids  into 
n^^hboriuii:  tissues  and  organs.  Thus,  for  exam])le,  a  car<'inonni  of  the 
i|unma  may  infiltrate  the  neighboring  fat,  .skin,  and  muscle;  one  of  the 
•jins,  the  nmxillaiy  l)one;  one  of  the  uterus,  the  vagina.  i)aramet  i  inm. 
lulder,  and  rectum;  a  cancer  of  the  gall-bladder  may  invohcthe  li\ci-; 
<le  of  the  thyroid,  tlie  trachea;  and  one  arising  in  the  l)ionchi,  the 
lliigs,  etc. 

!  The  formation  of  metastases  may  take  i)lace  eithei-  through  the 
1  nph-  or  blood-vessels,  and  is  of  very  frequent  occnn-ence  by  ixith 
iiites.  It  leads  to  the  development  of  secondary  nodules  in  dill«'rcnt 
«,'ans;  but  it  may  happen  that  large  lyni])hatic  areas — as.  for  exaniph-. 
tj  lymphatics  of  the  lung — maybe  simjjly  dilated  by  the  new  growth, 
vthout  the  foiination  of  circumscribed  nodnU's,  The  tianspurtatitui  of 
(■  icer-<'ells  to  the  Ixtne-iuariow  may  lead  t<»  a  carcinomatous  degener 
ann  of  the  mariow  of  an  entile  bone  or  of  several  as.socialed  l)oMes. 
3treover,  it  should  be  noted  that  ]>robal)ly  not  every  transportation  of 
cicer-cells  is  followed  by  the  development  of  a  cancer,  but  tliat  many 
tithe  cells  so  1iansi)Ianted  die. 

The  tissue  of  a  carcinoma  is  sometimes  white  and  soft  like  marrow, 
snetimesfirm  and  dense;  but  it  is  ahnost  always  possii)le  to  obtain  fiom 
t  ;  cut  surface  more  or  less  of  a  whitish,  cloudy  fluid  called  nmcrr  Jnirr 
**  raurrr  )iiill\  Very  often  the  cut  suiface  presents  a  tough,  lilirons 
f  luework  in  the  meshes  of  which  the  softer  masses  lie;  and  from  which 
li'  latter  may  be  squeezed  out  by  i»ressure  either  in  the  form  of  tluid,  or- 
apings  or  as  crnnibling  masses. 

Themas.s<'S  obtainedfrom  thecut  surface  tliiough  pie^vure  and  scrap- 
if  consist,  for  the  chief  ])art.  of  atyplcally  proliferatinv:  epithelial 
c^s,  the   .so-called   cancer-cells,  which   aie  fouiMl    in   a  ;/rr,it   niri>ti/n/ 

'  j\mx,  and  usually  show  (h'generati\<'  changes,   particularly   fatiN    de- 

'Kieration.     A  true  seciHion  of   these   epithelial    cells    is    usually    not 
fJind;   but    cancers    occui- — i)articularly    in    the    mucous   mendnanes. 

foirie.s,  mammary  glands,  and  fhyi<»i<l— which  i)rodnce  mucin,  jix-udo- 
iiicin,  or  colloid.'     Theamount  of  secretion  may  at  times  be  so  abundant 

t^ta  lead  to  the  formation  of  cysts  and  thereby  to  riffilonirrinoiiKi. 

i    jRetrograde  changes  occur  very  often  in  cancers  at  an  early  stage. 


I 


458  TUMORS. 

They  are  caused  partly  by  the  feeble  vitality  of  the  new  growth,  part 
by  circulatory  disturbances,  which  may  be  due  to  the  hlling-up  of  capr 
laries  aud  veins  by  the  ingrowing  cancer-cells,  and  partly  by  extern 
causes.  These  changes  lead,  in  the  first  place,  to  a  destruction  of  cancc 
cells  in  certain  portions  of  the  tumor  and  the  formation  of  ceutui 
cavities  due  to  the  liquefaction  of  the  dead  poitions,  so  that,  after  H: 
sorption  of  the  dead  material,  the  tissues  often  sink  in,  and  in  this  W;| 
depressions  are  caused  over  the  surface  of  the  tumor-nodules.  Such  c 
jiressed  areas  are  seen  i)articularly  upon  primary  cancer-nodules  in  t; 
jnammary  gland,  and  on  secondary  nodules  in  the  liver,  lungs,  a^ 
other  internal  organs,  and  are  often  sfjoken  of  as  cancer-umbilications. 

The  retrograde  changes  often  lead  to  complete  destruction  of  tuiiK- 
tissue,  and  thereby  to  the  formation  of  ulcers.  This  occurs  particulaij 
in  cancers  of  the  mucous  membranes,  these  growths  at  the  patieni; 
death  usually  revealing  a  more  or  less  extensive  ulceration ;  but  sii,i 
ulcerations  also  take  place  in  carcinomata  of  the  mammary  glands  ail 
skin.  In  the  latter  situation  the  cancer  may  take  on  the  appearance  t 
a  rodent  ulcer.  The  edge  of  such  ulcers  is  sometimes  elevated  and  !• 
sembles  a  wall,  or  it  may  be  studded  with  nodules ;  at  other  times  iVi 
more  sharply  defined  and  only  slightly  infiltrated.  The  base  of  the  ulir 
is  sometimes  fissured  and  ragged,  and  covered  with  necrotic  tissue; it 
other  times  it  is  smooth.  ' 

The  view  that  the  cause  of  carcinoma  and  sarcoma  is  to  be  found  in  parasis 

still  finds  adherents,  although  the  investigations  of  recent  years  do  not  supportj. 
Publications  concerning  cancer  and  sarcoma  parasites  have  not  been  wanting  {Sanfei't:, 
Roncali,  Aievoli,  Maffuci,  Secchi,  Foa,  Ruffer,  Pliynmer,  Gaylord,  Wlaeff,  Sjdbri/, 
Schiiller,  von  Leyden,  Feinberg,  Leopold,  Podwyssotzki,  and  others),  but  in  the  majojy 
of  cases  proof  has  been  wanting  that  the  supposed  parasites  were  really  living  organis!;; 
or,  when  living  organisms  (yeasts,  rhizopods)  have  been  cultivated  from  tuni^, 
there  has  been  no  positive  proof  that  they  stood  in  any  causal  relation  to  the  gib 
neoplasm.  The  experiments,  in  particular,  of  Sanfelice,  Wlaeff,  Leopold,  and  Sjobig 
are  far  from  offering  any  convincing  evidence.  ' 

It  is  very  striking  and  worthy  of  note  that  nearly  every  author  has  found  a  diffe  it 
parasite  and  has  not  recognized  the  parasitic  forms  described  by  the  others,  'jis 
speaks  against  the  correct  interpretation  of  the  findings.  Moreover,  in  the  case  of  jie 
majority  of  the  formations  described  as  parasites  another  interpretation  is  poss6.j^; 
Some  of  them  are  degenerating  leucocytes  or  the  remains  of  such  enclosed  in  ca,nf-{ 
cells;  others  are  vacuoles,  hyaline  or  mucoid  products  of  the  cancer-cells,  or  dege|?' 
ating  nuclei  or  cell-division  figures,  or  fragments  of  these.  Only  rarely  is  it  imposile 
to  give  a  satisfactory  interpretation  of  the  findings,  but  this  fact  is  not  sufficient  groijis 
for  ascribing  a  parasitic  nature  to  the  formations.  The  attempt  to  compare  the  "b ;'« 
eyes"  of  von  Lej^den,  or  the  Plimmer's  bodies,  to  which  they  correspond,  withb 
parasite  found  in  the  root-tumors  of  cabbage,  the  Plasmodiophora  hrassicce,  amm 
regard  these  root-tumors  as  analogous  to  cancer,  is,  likewise,  without  justification,  fWi 
the  two  diseases  have  scarcely  anything  in  common.  The  plasmodiophora  multiijM' 
within  the  plant-cells  and  distends  the  latter.  Only  after  the  destruction  of  the  affe^i 
cells  does  a  regenerative  proliferation  occur  in  the  neighboring  cells.  In  cancer  thejis  ~ 
from  the  very  beginning  an  unlimited  and  at  the  same  time  an  infiltrative  grow'jof 
tissue-cells. 

The  natural  history  and  clinical  behavior  of  cancer  are  not  such  as  to  raai'jt 
l)ro])able  that  it  is  of  parasitic  nature.  The  formation  of  cancerous  tumors  as  a  rp 
of  disturbances  of  development  speaks  against  this  view.  The  metastases  de'pP  i 
from  transported  tumor-cells,  and  cell-inclusions  are  not  necessary  to  their  formal. 
The  tiimspiantation  of  cancer  and  sarcoma  into  animals  of  the  same  species,  anCjM 
implantation-cancers  occasionally  observed  after  operation,  are  the  result  whobO' 
the  traiis|)lantation  of  living  tumor-cells,  and  cannot  be  used  as  arguments  in  <>' 
of  the  parasitic  theory.  If  protozoa  are  the  cause  of  cancer  we  must  assume,  acco  n? 
to  om-  present  knowledge  of  these  parasites,  that  a  given  species  can  find  a  suitabl'"" 
only  in  a  certain  variety  of  epithelium.  Cases  of  transmission  of  cancer  from  m  to 
man  occasionally  cited  as  evidence  can  be  utilized  hypothetically  in  support  c;h« 


j 


CAHCIXOMA.  459 

irasitic  thojry  only  when  the  c;inci'r  dovclops  in  tlic  jilTcclcd  indiviiliial  in  tiic  sarno 
other-tissue. 

To  increase  our  knowledge  concerning  liie  cause  of  cancer  a  committee  was  appointed 
.  study  the  statistics,  and  throu>,di  a  collective  investijjation  on  October  loth,  I'HM), 
tempted  to  determine  the  number  of  liviiii;  cancer-patients  in  (lermany.  In  so  far 
;  the  view  of  the  parasitic  nature  of  cancer  is  concerned  this  work  was  nefjative,  since 
only  .S.()  per  cent  (of  12.1 7!t  cases)  was  an  infection  suspected.  A  hereditary  Irans- 
ission  was  thou,<:ht  possible  in  17  per  cent,  but  the  number  was  reduced  to').:i  per 
nt  when  the  possibility  of  such  an  inluritance  was  limited  to  tlu).se  c;i.ses  in  which  the 
me  organ  was  affected.  Since  ISSS  th.e  number  of  cancer-ca.ses  is  siiid  to  have  in- 
eased  about  a  third,  but  even  this  statistical  evidence  is  with.out  sipnificance  since  it, 
ay  be  satisfactorily  exj^lained  as  the  result  of  fjreater  skill  in  diagnosis  as  well  as  the 
suit  of  an  increase  in  the  average  length  of  life.  .Moreover,  it  shouKI  be  noted  that 
en  now  many  c^i.ses  of  cancer  (cancer  of  stomach)  are  not  diagno.sed  even  >ip  to 
•ath,  and  on  the  other  hand  ca.ses  are  regarded  as  cancer  when  occurring  in  tissues  in 
hich  carcinoma  does  not  develop.  (The  statistics  mentioned  above  contain  2U1  cases 
■  primary  carcinomata  of  the  bones.) 


Literature. 

(Etiolofin  of  ('(irciiKniiK.) 

Iberts:  Das  Carcinom,  Jena,  1S87. 

polant  u.   Emden:  Natur  der  Zelleinschlus.se  in  Carcinomen.     Zeitschr.  f.  IIvg.,42 

Hd..iyo;i. 

Arcy :  Some  Effect  i  of  Chronic  Irritation  upon  Living  Ti.ssues.     British  Med.  Journ., 
j      ii..  1893. 

linaghi:   Blastomyceten  in  Epitheliomen.     Zeitschr.  f.  Ilyg..  xxiii.,  1896  (Lit.). 
jorrel:   Sur  la  signification  des  figures  d^crites  comme  coccidies.     Arch.de  med.,   ii., 

1890. 
lose:   Le  cancer,  mal.  infect,  a  sporozoaire.     Arch,  de  phys.,  x.,  1S9S. 
irosch:  Genese  der  malignen  Geschwulste.     Virch.  Arch..   1()2  Bd..  1900. 

urchardt:  Ein  Coccidium  im  Schleimkrebs  des    Menschen.     \ireh.  Arch.,  131  Bd., 
1S93. 

haintre:    De  I'epithelioma  des  cicatrices.     Lancet,  ii.,  1889. 

laessen:   leber  die  in  Carcinomzellen  gefundenen  Einschlus.se.     Beitr.  v.    Ziegler. 
,      .\iv..  1S93. 

larke:   ( )bservat.  on  the  Histol.  of  Cancer.     Cbl.  f.  Bakt.,  xvi.,  1894. 
•ebenedetti:   Eziologia  del  cancro,  Torino,  1887. 

abre-Domergue:   Les  cancers  epitheliaux,  Paris,  1898. 

einberg:   Die  Gewebe  des  Menschen  u.  die  Krebsgcschwidste.  Berlin,  190.3. 

irket:   De  I'origine  du  cancer.     Ann.  de  la  Hoc.  beige  d.  microsc,  xvi.,  1S91. 

oa:  Sui  parassiti  et  sulla  i.stologia  patologica  del   cancro.     .\rch.  per  le  Sc.   Med., 

xvii.:   Arch.  ital.  de  Biol.,  xx.,  1893. 
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[       1899. 

fraylord:   The  Protozorin  of  Cancer.     Amer.  .Journ.  <>f  Med.  Sc.  Iliol. 
[rreenough:    Plimmer's  Bodies  in  Carcinoma.     .Jciuii.  Bc,>i .  Soc.  .M.-d.  Sc.  190(1;   Cell 
I       Inclusions.     Journ.  of  Med.  Res.,  1902. 

jiauser:    Das  chron.  Magengeschwiir,  sein  Vernarbungsproce.ss  u.  de.ssen  Bezieh.  zum 
.Mager.carfinnm,    Leipzig,    1883;    Das  Cylinderepithelcarcinom  d.   Magens    u.  d. 
I);irms,  Jena,  1890. 
londa:  Z.  parasit.  Aetiologie  d.  Carcinoms.     \.\..  171  Bd..  I".M);>. 
srael:    Das  Problem  d.  Kreb.satiologie.     A.  f.  klin.  Chir..  (i7  Bd..  1902. 
^arg:    leber  das  Carcinom.     Dent.  Zeit.schr.  f.  Chir.,  34  lid..  1892. 
Xlimenko:   Feinbergs  Krebsparasiten.     C.  f.  a.  P.,  xiii.,  1900. 
..ack:    I'.xperim.  Production  of  Cancer.     Journ.  of  Path.,  vi..  1899. 
Le  Count.  Analogies  Between  Plinuner's  liodies  an<l  Certain  Structiucs  fotm.l    Xor- 
;       iiially  in  the  Cytopla.sm.     Journ.  of  Med.  Pes.,   1902. 
Leopold;   Aetiologie  d.  Carcinoms.     Arch.  f.  fiyn..  01  lid..  1900. 

■.  Leyden.   Aetiologie  des  Carcinoms.     Z.  f.  klin.  Med.,  43  Bd..  1901 .  u.  .")2  B.I..  1904: 
Krel;s))arasiten       Z.  f.  Krebsfor.schung.  i..  1904;     Bericht  uber  <lie  vom   Komitec 
j       fur  Krel)sforschung  am  15  Okt.  1900  erhobcne  Sammelforschung.  Jena.  1902. 
■.  Leyden  u.  Schaudinn:  Leydenia  gemmipara.     Sitzbcr.  d.  Akad.  d.  \\  is,s.,  Berlin, 
1890. 


460  TUMORS. 


Liebe:   T'eber  den  Paraffinkrebs.     Schmidt's  Jahrb.,  236  Bd.,  1892. 

Liubarsch:  Patholog.  Anatomie  u.  Krebsforschunsr,  Wiesbaden,  1902. 

Nichols:  First  Annual  Report  on  the  Etiology  of  Cancer.     Joiirn.  Bost.  Soc.  M. 

Sc.  1900;   Second  Report.     Journ.  of  Med.'  Res..  1902. 
Nosske:    Pie  als   Parasiten  gedeuteten  Zelleinschliisse,     Deutsche   Zeit.   f.   Chir..l 

Bd.,  1902. 
Petersen  u.  Exner:   Hefepilze  u.  Geschwulstbildung.     Beitr.  v.  Bruns,   xxv.,   18. 
Pfeififer:   I'ntersuchungen  (iber  den  Krebs,  Jena,  1893.  ; 

Pianese:  Beitr.  z.  Histologic  u.  Aetiologie  d.  Carcinoms,  Jena,  1896. 
Plimmer:   On  the  Etiology  and  Histology  of  Cancer.     The  Practitioner.  1899,  1900 
Podwy ssotzki :    Parasitare    MyxomvcetengeschAviilste.    Zeit.    f.  klin.  Med.,  47  E, 

1902. 
Reichelmann :    Krebsstatistik  v.  path.-anat.   Standpunkt  aus.     Berlin,  klin.  Wo(', 

1902. 
Roncali:  Aetiologie  dcs  Krebses.     Cbl.  f.  Bakt..  xxi.,  1897. 
Rosenthal:   Mikroorganismen  in  Geschwiilsten.     Zeitschr.  f.  Hyg.,  v.,  1889. 
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1896. 
Ruffer  and  Plimmer:    Parasitic  Protozoa  in  Cancerous  Tumors.     Journ.  of  Path.,!, 

1892:    ■;..  1SS3.  ; 

Sanfelice:  Wirkung  d.  Blastomyceten.     Zeitschr.  T.  Hyg.,  xxi.,   1895:    xxii..    IS';; 

xxix.,  1898;  xhv.,  1903.  '  I 

Schiiller:   Zur  Aetiologie  d.  Geschwiilste.     Cbl.  f.  Bakt.,  xxvii.,  1900.  I 

Schulthess:   Statist.  Unters.  lib.  d.  Aetiologie  d.  Mammacarcinoms.     Beitr.  v.  Bru', 

iv.,   1881.  ; 

Schutz:    Protozoen-  u.  coccidienart.  Mikroorganismen  in  Krebszellen.     Miinch.  mi. 

Woch.,  1890.  i 

Schwarz:   I'eber  den  Carcinomparasitismus,  Wien,  1895.  i 

Sjobring:  Mikroorganismen  in  Geschwiilsten.     Cbl.  f.  Bakt.,  xxvii.,  1900,  u.  Langi- 

becks  A.,  65  Bd.,  1902.  ; 

Spirlas:  Verdauungsvakuolen  u.  ihre  Bez.  zvi  Foa-P!immerschen  Krebsparas.     Miinl. 

med.  Woch.,  1903.  i 

Steinhaus:   Ueber  Carcinomeinschliisse.     Virch.  Arch..  126.  127  Bd.,  1891.  '■ 

Sternberg:    Zelleinschlusse  in  Carcinomen.     Beitr.  v.  Ziegler,  xxv.,  1899  (Lit.);   Aei- 

logie.     Wien.  med.  Ztg..  1903.  j 

Steven  and  Brown:   On  the  So-called  Parasitic  Protozoa  of  Cancer.     Journ.  of  Pa  i, 

ii.,  1893.  ! 

Strobe:    Histogenese  u.  Aetiologie  des  Carcinoms.     Cbl.  f.  allg.  Path.,  ii..  1891  (Li!; 

Die  parasitaren  Sporozoen  in  ihren  Beziehungen  zur  menschl.  Pathologic,  insli. 

zur  Histogenese  u.  Aetiologie  d.  Carcinoms.     lb.,  v.,  1894  (Lit.). 
Volcker:    Das  Wesen  der  Schiillerschen  Parasiten.     D.  med.  Woch..  1901. 
Volkmann:   Ueb.   d.   primaren  Krebs  d.   Extremitaten.     Samml.   klin.   Vortr.,     . 

334-335.  1900. 
Watzdorf:   Verbreitung  der  Krebskrankheit  im  D.  Reiche.    D.  med.  Woch..  1902.  J 
WlaeflE":   Role  des  Blastomvcetes  dans  I'organisme.     Soc.  An.  Paris,  1900;   Cbl.  f.  a". 

Path.,  1900. 
Zenker:   Der  primare  Krebs  der  Gallenblase  u.  seine  Beziehung  zu  Gallensteinen- 

Gallenbla-sennarben.     Deut.  Arch.  f.  klin.  Med.,  44  Bd.,  1889.  ■ 

See  also  §  122.  ! 

§  122.  The  development  of  carcinoma  of  the  skin  takes  place  mi 
often  from  the  surfacr  epithelium,  ami  is  cliaracterized  es.sentially  by  t'J 
growth  of  the  iiilerpapillai y  portions  of  the  same  into  the  deeper  p.- 
tions  of  the  skin,  in  the  foi-m  of  epithelial  |>luos  (Fig.  ,S;U,  d)  which  1 
lip  the  connective-tissne  spaces.  The  stratnm  corneum  (c)  may  a*) 
undergo  hypertrophy  along  with  the  cells  of  the  rete  Malpighii,  ajl 
penetrate  into  the  deeper  tissues  with  the  epithelial  plugs  (d).  Mdj- 
over,  the  horny  cells  which  get  into  the  deeper  tissues  may  form  epithel  1 
pearls  (e). 

Besides  the  surface-epithelium,  the  epitheiiion  of  the  hair-foUieles  ai 
sebaceous  glands  may  also  take  part  in  the  development  of  the  cane,; 
and  there  occur  carcinomata  of  the  skin,  which  develop  entirely  fr 


u 


DKNKLOI'.MKXr    OK    (  AK(I\()MV.  401 

lu' st^ba('0(»iis  ulaiids,  and   tlicrcforc   slioiild    he   cImss.mI  witli    ihr   -land- 
aiicers. 

The  conurrtirr  tisHiw  may  roiuaiii  oiitiicly  passive  diiiiiij;-  the  iri-iowni 
f  Ww  opitlu'limn.  but  is  sooner  oi-  lalei-  oxcited  lu  «rrnwlli  (Kiu.  ;{:{|.  a  ). 
iid  tlie  i)ai»illu'  often  develop  into  loni;,  Inanclicd  lorniat  ions  (  /"   .'     In 


t7-' 


f 


w 


)U 


..P- ,  :.  :,■■,  :^^::.|^ 


-:^-'^l'M^m. 


Fig.  334— Transverse  section  through  a  carcinoma  of  the  lip  (alcohol,  hspniatoxvlin.  eosin).  a.  Corluni, 
a  slate  ot  pntlifcration  ;  ?«,  opithpliuin  ;  v.  thickened  liorny  laver;  (?,  epithelial  pint's  extcndins.'  iiii<i  the 
riuui;  c,  epithelial  phiirs  with  horny  pearls,  cut  otiliiinely  ;  /.  enlarfred  papilhe.     ;•.  i~. 

le  proliferating- eon nective  tissne  tliere  are  often  found  in  association 
itli  the  JibrohJo.sfs  also  Joicori/fr.s  and  Ij/mp/ioct/trn,  Miiioh  may  penetrate 
ito  the  epitlielinm.  They  become  es])ccially  nnim-rons  in  thcexcnt  of 
ssue-ch'strnction,  so  that  under  such  circnins1an<'cs  the  piolit'crat  ion  of 
If  connectixc  tissne  acquires  wholly  the  character  of  an  iidlammatory 
mulation-t  issue. 

The  origin  of  the  carcinomata  arising  from  mucous  membranes 
)vered  with  squamous  epithelium  ina\  he  the  same  as  that  of  a  <an 
r  ftf  the  skin  —  that  is,  it  is  iiit  rodueed  \)\  .i  j>roli/cra(ioii  of  the  siir/ticf 
titheUiiin  (Fi<i.  ;>35,  ((,  c).  If  yhnids  are  present  they  may  also  tahr  part 
the  dercJopmcnt  of  the  cancer.  It  is  a  remaiUaI)le  fact  that  in  the  for- 
ation  of  such  atnmor,  ,ulan<ls  witli  cylindrical  epithelium  may  furnish 
>ithelial  products  Avhich  correspond  wit  h  those  (»f  the  snrface  epit  he 
mil.  The  ei»ithelial  iiroliferation  may  at  lirsl  be  int  racaiialicnlar  and 
ul  to  a  dilfnse  thickening;  and  stratification  of  the  e|)itlieliiini  (l-'ij:. 
{.'),  f),  <n- to  the  formation  of  excrescences  (<•).  baler,  the  proliferal  in<; 
ithelium  breaks  into  the  connective  tissue. 

The  connective  tissne  beliaves  in  the  same  manner  as   in  i  he  <ase  of 
nicer  of  the  skin. 
Tlie  cylindricaUcelled  carcinomata  of  the  mucous  membranes  ari.s«- 
the  <-ase  of  llie  intestine  from  the  Itihidar  iilaiids  or  from  the  cnii'l''.  t  he 
ithelinm  of  which  at  lirst   nnderji-oes  an   active  inoliferalion.  and   be 
»nie,s  .stratified,  Avhile  the  f,dands  become  dilated  (  I-'i-.  :{:;«;,  h).      baler. 
le  glands  become  clian<;ed  into  branching-,  atypically  formed  ^hnelnres 
),  whicli  ])ossess  an  ei)itlielinm   arran.iie<l   in   maiix   la>er>,  an<l    which 
ow  into  the  n«'ijihborin«;-  tissues. 

In  the  stomach  the  gastric  <ilands  chan-e  l  heir  characler  iV'v^.  .V.\~ . 
),  and  then  thron.iih  a  continued  j^rowth  iidilt  rate  I  he  >ubnnn-osa  (//), 
emnscnlaris  (d).  ami  the  serosa  (r). 


462  TUMORS. 

The  epithelium  of  the  newly-formed  glands  stains  more  deeply  -w  h 
nuclear  stains  than  does  normal  epithelium. 

The  connective  tissue,  as  in  the  case  of  cancer  of  the  skin,  sooner'r 
later  proliferates,  and  in  connection  with  this  proliferation  there  ii  v^ 
occur  also  an  emigration  of  leucocytes  and  lymphocytes. 

The  development  of  cancer  in  glands — as,  for  example,  in  the  nw:- 
mary  gland — likewise  begins  with  an  epHherud  proJifemtion,  as  the  resjt 
of  which  the  glands  (Fig.  338,  a)  become  widened,  altered  in  form  (|, 
while  their  lining  epithelium  becomes  stratified  (b).  AVitli  the  break* 
through  of  the  epithelium  into  the  neighboring  connective-tissue  spacl 
the  epithelial  infiltration  of  that  tissue  is  begun.  According  to  fe 
structure  of  the  gland  in  which  the  cancer  arises,  and  according  to  je 


o  ..  -^ 


e  ^- 

r 


Fig.  335.— Rcpinninsr  clevelopincnt  of  carcinoma  in  the  vagrinal  portion  of  tlio  uterus  (alcohol,  Bisin  jt 
brown).  «,  Kpithelium  ;  /;.  coiiiicctLvc  tissue;  c,  surface  epithelium  frrovvintr  into  the  deeper  tissue 'n, 
dilated  glands ;  r,  frlandular  ei)ithelinni  jrrowinur  out  in  form  of  plutrs:  /,  cross-section  of  a  glam  pt 
cylindrical  eiMlheliiuu  of  wliicli  has  become  converted  into  sti'atilled  epithelium.     >;  45. 


variety  of  the  cancer  itself,  there  will  l)e  produced  varying  microscop'il 
pictures. 

The  connective  tissue  of  the  gland  through  proliferation  also  ta,?S 
part  in  the  building-up  of  the  tumor;  but  in  the  early  stages  of  develp- 
ment  such  proliferation  may  be  slight  or  entirely  wanting.  ] 

The  development  of  a  carcinoma  in  an  adenoma  or  fibro-adeD(ia 


Fi;;.  339,  a)  is  likewise  initialed  l.y  a  eiian-e  in  tlie  cliaraeler  of  H,,' 
I'llsand  by  a  inon-  active  pni/i/'mition  <>/ (hr  rpif/,Hi,iiii,  thntn-;!!  wliieli  llie 
imple  eitillielium  beeduies  stiatilied  ( /;,  r).     The  laler  in^n.wili   «.|"  tji,. 


i)i:\  i:i-(H'.Mi:\i    ui 


Al»(    l\(>\IA. 


4()3 


kS^M 


Fig.  SW.— nevelo|)iiiir  ailcnoiMrciiKnua  nf  t 
rosa  with  iinrhaiigeii  ghuuls;   h,  {.Maiiiis  show  ini.' 
I  iiiiiiitHii.    X  100. 


mall  Ills  ureas  ill  thu 


4ithelinni  into  tlie  connective  tissue,  Aviiieli   often  (.ccnrs  at  a    \ei y  latr 
ijre.  is  a  fmtlier  si.un  of  niali.unancy— tiiat   is,    of  Hi,,  eaivinoniatons 
l|insfoiniation  of  tlie  new-oiowtli. 


Fig.  337.— .Aflfnoiardnoina  of  stomach  In  pron^ss  of    (li-vi-loiiiiicnt  (furiimlln.  alcnhnl.  haniatn.wiin. 
n».    <i,  Miiciisa  ;  /<,  iiiii.s<'ularls  miicosie ;  c,  .subiimctwa ;  </.  iiiiiwtiluh.t ;  «•.  scnwu  :  J.  i/,  u<li-n<«iininutnu. 

The  development  of  carcinoma  from   papillary  epitheliomata  lakes 
W'e  in  the  same  .manner  as  from  tlie   normal   .skin  and   niniuns  mem 


4G4 


TUMORS. 


braiies ;  and  is  characterized  especially  by  the  iuliltration  of  the  ep 
liiiiu  into  the  basement-tissue  upon  which  the  epithelioma  rests. 


^  'ir\.. 


^^^^ 

$^^' 

' '..  i  '  ' 

:K-' 

,,  \''  -" 

''^'"  A 

' '( '  ' 

\'  4--.  >'' 

:-^.<^^ni>'^ 


Fig.  338  —Developing  cystocarclnoina  of  mamma  (alcohol,  lu^matoxylin).    Tumor  of  the  size  of  lljean. 
o,  Normal  gland-tissue ;  /*,  proliferating  glaud-tissue.    X  100.  I 


I  "■" 


^ 


^^lu^S^S^i 


Fk    J3J  — Tubnl  ir  t(l(  II  m  i  of  nnuinm    li  ui 


,un,n_.Mnu.  nt       ..   in  ,  .    f  nn.l  hania 

toxvlin)      fl    HruKliin     ^liiiltutuU     uuli     iiii)  It      |  itli  luiiu      Hit    i    ii    m  ill  ulir  ""'"^*lr,t 

H   lif  ritmt,  in(i\ti\  (ilhilii     /    (    ^liu  i  tubule    tin   ipithUuiii    f  \Min  h  i    i  mu  iiiipk   pi    s"^'"' 

Ilea.     >:  100.  ! 


1 


I)KVKI.()l'Mi:\l-    ()!•    CAK'CINOM  \. 


k;.-) 


Tlio  development   ot  carcinoma  from   transplanted   or  misplaced 
I  epithelium  or  from    remains  of  fcctal  structures  |.i  ..(«•. ds  in   i  Iw  same 

iiiaiiiicr  as  tlia!    «•!'  cartiiioiuata  aiisin-    in   rillicr  Miilacf   ur  <,'lantiular 

rpitlu'liuni. 

'  Carcinomatous  proliferations  of  the  cell-layer  and  the  syncytium 
|of  the  chorion,  l)()lh  of  wWwh  aiisr  Irom  ilu^  fa*tal  ectoderm  (  Konnd  ), 
I  may  urciii-  citlKT  in  the  chorion  of  youiijj:  *>v:i  or  in  llic  placmla  of  ollirr 
jcnibryos,  and  in  uty])ieal  cases  arc  characlt'ii/cd  hy  a  mixlnrc  of  tli.-  two 

forms  of  cells  {F\g.  MO,  a,  h).     They  <;ro\v  into  the  neighboring;-  uteriuo 


/^•••••.' 


•.*>*Cv. 


gp«jp;a**^S.%,- 


Fig.  340.— Intriivascular    epithelial    pluK   of   a    i.lacenlal     caiciiiotna.     (Formalin,     alcohol, 
smatoxylin.  eosiii.)     a,  Derivatives  of  the  cell-laver;    /j,  .^viuytial  tell.w;   c.  wall  of  l.li)<>(l-vi-.s.s«-l; 
blood.     X  40. 

s.sue,  i)arlicnlarly  into  the  blood-vessels  of  the  uterus  (r),  and  may 
lirou«,dM he  formation  of  thrombi  lead  to  extensive  destruction  of  llu' 
ssues  of  the  nteins,  and  may  j;ive  rise  to  metastases.  Tilyxomalons 
•jiencration  of  the  chorion  oi']>l:»<"<'"bil  villi  i  liydati<l  mnle  )  appears  lo 
ivor  the  de\cl()pment  of  snch  carcinomatons  jiiowtlis. 

The  development  and  growth  of  carcinoma  l-.ivc  l.'-.n  in  nrcnt  years  tli«» 
>\(tcl  of  scarcliiiiir  invcstiiiatioiis.  Hcsidcs  Hlblnrl  ami  H-rst,  who  linve  «-xi>rc-.ssc. 
leir  views  in  their  works  on  tumors.  Krumpcrhrr.  I/nusir,  I'rdrsm  aiitl  i'lihiurn.  -.wvX 
orrmann  have  |)iil>lislie(l  treatises  of  consi(icral)le  si/e  upon  then*'  <|iiestioiis.  ,\ll  of 
lesc  writers  aiiree  tliat  the.(levelo|)iiiK  neoplasm,  in  so  f:ir  as  its  epitli.-li.ii  element.s  uro 
)nceme(l.  grows  throntrh  its  own  resources  and  does  not  e.xcitc  t»i<ii<it:hl..-niiv'  ii^i-iui-. 
lat  is.  neiKhborinfi  epithelium,  tf)  a  cancerous  ])roliferation.  The  nci>rhl.i.nii«  tissue 
in  part  compressed  an.l  in  part  infiltrated.  On  the  other  han<l.ditT.T.-ne.-s  of  omnion 
ist  conccrninK  the  l)e!;innin{:  of  the  cancerotis  growth.  .\ccordinK  to  llaiisrr,  hnim- 
cher,  Petersen  and  Colmers,  tlie  dcveIoi)ment  mav  be  unicentric  or  multic«-ntric.  in  the 
tter  case  starting  in  several  places  in  the  ei)ithelium.     Jiorrmtmn  assumeH  u  unicentric 

30 


466  TUMORS. 

origin;  in  those  cases  in  which  the  development  apparently  proceeds  from  several  pi  jj 
he  assumes  that  there  is  a  coincidental  development  of  several  primary  cancers. 

According  to  Hauser.  Krompecher,  and  Petersen,  with  whom  I  agree,  the  deve> 
ment  of  carcinoma  takes  place  from  cells  of  the  superficial  epithelium,  hair-foUiig, 
glands,  and  gland-ducts.  According  to  Borrmann,  a  developing  carcinoma  is  a  groTig 
cell-complex,  which  existed  as  such  before  it  began  to  grow;  it  is  an  isolated  embryi^ 
cell-complex.  Squamous-celled  cancers,  although  not  all  of  them,  arise  from  extrecly 
small  cell-complexes  that  lie  within  the  superficial  epithelium,  and  probably  beca'e 
isolated  during  foetal  life  through  a  closure  of  a  furrow  or  through  some  other  anomalljf 
development.  j 

According  to  the  first-named  authors,  the  pathological  new-formation  has  itsoiin 
from  epithelium  or  at  least  takes  its  point  of  departure  from  it.  According  to  Borrrrcn 
and  Ribbert,the  process  begins  with  inflammatory  changes  in  the  connective  tise; 
in  the  skin  these  may  be  caused  by  a  retention  and  infection  of  the  secretion  of!ie 
sebaceous  glands  causing  an  elevation  and  stretching  of  the  epithelium.  As  the  re  It 
of  this  stretching  and  the  accompanying  hypersemia,  the  included  foetal  cell-comi'a 
proliferates  and  grows  into  the  deeper  tissues.  i 

The  independent  proliferations  of  the  foetal  ectoderm  are  at  this  time  usv-iy 
designated  as  chorioepithelioma  (Marchand)  in  accordance  with  the  view  that  tW 
represent  an  epithelial  proliferation.  There  is  no  reason  for  not  classing  them  jih 
the  carcinomata,  since  they  are  characterized  by  an  epithelial  proliferation  whicl!a- 
filtrates  the  neighboring  tissues.  The  metastasis  through  the  blood-vessels  wjih 
characterizes  the  chorionic  carcinomata  occurs  also  very  frequently  in  other  carcjO- 
mata,  for  example,  carcinomata  of  the  stomach. 

Carcinomata  arising  in  the  skin  or  mucous  membranes  are  often  called  cancros, 
a  term  used  to  distinguish  them  from  other  carcinomata,  the  origin  of  which  M 
formerly  thought  to  be  from  connective  tissue.  \ 

To  a  certain  extent  the  character  of  the  parent  tissue  is  preserved  in  cancer-ds, 
but  a  careful  examination  shows  in  all  cases  that  there  is  a  certain  amount  of  ch«;e 
both  in  their  morphological  and  in  their  physiological  character  (arjaplasia).  This 
shown  in  changes  in  the  form  and  structure  of  the  cells,  their  changed  behavior  tcrd 
stains,  in  an  altered  position  and  arrangement  of  the  cells,  and  in  their  changed  ',&• 
tions  toward  the  surrounding  tissues.  ; 

The  traumatic  displacement  of  surface-epithelium  in  wounds  may  lead  tojhe 
formation  of  the  so-called  traumatic  epithelial  cysts — that  is,  cysts  varying  in:ze 
from  that  of  a  hemp-seed  to  that  of  a  nut,  which  are  lined  with  epithelium,  and,  in;.se 
they  arise  from  the  epitlermis,  contain  a  pultaceous  mass  of  desquamated  epithelfli. 
They  occur  most  frequently  after  puncture- wounds  of  the  volar  surface  of  the  fingenjod 
in  the  hollow  of  the  hand.  : 

Literature. 

(Gf'ucsi.s  of  Carcinoma.) 

Bandler:  Chorioepithelioma.     Amer.  Journ.  of  Obst.,  1902. 

Bayha:   Lupuscarcinom.     Beitr.  v.  Bruns,  iii.,  1888. 

Behla:   Die  Carcinomliteratur  bis  1900,  Berlin,  1901. 

Beneke:    Neuere  Arb.  z.  Lehre  v.  Carcinom  (1886-89).     Schmidt's  Jahrb.,  234,  ]J2. 

Bonnet:   Syncytien  u.  Plasmodien  der  Placenta.     Mon.  f.  Gebh..  1903.  , 

Borrmann:  Das  Wachstvnn  u.  d.  Verbreitungweise  des  Magencarcinoms,  Jena,  |)ll 
Die  Entstehung  u.  das  Wachstum  d.  Hautcarcinoms.     Z.  f.  Krebsf.,  ii.,  1904 

Borst:   Die  Lehre  v.  d.  Geschwiilsten,  Wiesbaden,  1902. 

Bozzi:   Zungencarcinom  nach  Psoriasis.     Beitr.  v.  Bruns,  xxii.,  1899. 

V.  Brvmn:    Prim.  Krebs  d.  Extremitaten.     B.  v.  Bruns,  37  Bd.,  1903. 

Bvicher:   lieitr.  z.  Lehre  v.  Carcinom.     Beitr.  v.  Ziegler,  xiv.,  1893. 

Cullen:  Cancer  of  the  Uterus,  New  York,  1900. 

Fabre-Domergue:   Les  cancers  epitheliaux,  Paris,  1898. 

Fiessinger:    La    pathogeuie  du  cancer.     Rev.  de  med.,  189)^. 

Flamming:    Ueber  Bau  u.  Entstehung  der  Driisen.     Arch.  f.  Anat.  u.  Phys.,  IS,. 

Franke:   Carcin.  entart.  Epidermoid  des  Daumens.     Virch.  Arch.,  121  Bd.,  189C 

Frankel:  Vom  Epithel  d.  Chorionzotten  ausgeh.  Carcinom.  Arch,  f,  Gyn.,  48;(i-I 
Blasenmolen.  lb.,  49  Bd.,  1895;  Chorionepitheliom.  Encyklop.  Jahrb.  v.  E  en- 
burg,  ix.,  1900. 

V.  Franque:  Chorionepithelioma  malignum.     Z.  f.  Gebh.,  49  Bd.,  1903.  , 

Friedlander:   L'eber  Epithelwucherung  u.  Krebs,  1877. 


I 


VAKIKTIKS    OK    (Ain  IXOMA.  467 

xaylord:   Malii^nant  C.rowtlis  of  the  ChorionLc  Epithelium.     Aincr.  Joiirn.  of  Ohst., 

1S9S. 
Ilanseinann:   lebor  Msyminetrisclie   ZelltheiUine;   in  Kpitlielkrel)sen.     Vircli.  Arch., 
i        111)  H(l..  18Si);    Die  mikmskoi).  I)iagno.><e  l)usar(i«er  (Icscliwiil.ste,  Ik-riin.  1U02. 
lauser:   Das  Cylimleiepithelcarcinom  des  Mafrcii.s  u.  des  ni?kilaniis.  Jena.  ISIK);  lli.s- 

togenese  d.  Krebses.     Virch.  Arch.,  i:?S  Rd..  ISO-J.  141  Hd..  IN!).'');  Tolypo.M.s  in- 

testinalis  ackMiomatosa.     Deut.  Arch.  f.  kiln.  Med.,  ,">.'  i^l.,  1,S9.');  Histopene.se  de.s 

Plattenepithelkrebses.     Beitr.  v.  Ziegler,  xxii.,  IS'.IT;   Neue  .\rb.  ui)erd.  Carcinoni. 

Cbl.  f.  all?;.  Path.,  ix.,  1808;  Primiire  z.  Geschwulstbilduns;:  fiUu-.  lOpitlielerknmkunK, 

B.  V.  Ziejiler,  IV.i  Bd.,  lOOii. 
ieidemann:   Bedeut.  d.  kleinzeUigen  Infiltration  in  Carcinonien.     Vircli.  .Vrch.,  129 
I       Bd..  1892. 

srael:   Ueber  die  ersten  Anfano;e  des  Majrenkrebses.     Berl.  klin.  Woch.,  1N<.)(). 
nng:  Zur  Lehre  voin  Carcinoin.     Langenbeck'-s  .Vrch..  ol  Bd.,  18"?."). 
.  Kahlden:    De.struirende  Placciitarpolvpen.     Cbl.  f.  allj:.  Path.,  ii.,  18<.(1. 
larg:    Tcber  da'^  Carcinoni.     Zoiischr.  f.  Chir..  M  lid.,  18<>2. 
iLrompecher :   Der  Ba.salzelien-Kreb.s,  ,Jena,  HIO.S. 

jinser:   Kpitholioin  u.  Carcinom  in  Dermoidcysten.     B.  v.  Bruns,  .'U  Bil..  I'.Mil. 
mbarsch:   Priiiiiirer  Krebs   des    Ileums  (Carcin.  cvlindroniatosuni).     \'ircl'..  .\rch., 
;       111   Bil..   1S88. 

larchand:  Deciiluale  rie.^chwiilste.     Mvinatsschr.  f.  debh.,  ISO.'S. 
lertens:   Carcinom  a.  d.  Boden  e.  Dermoids.     B.  v.  Bruns,  xxxi..  1001. 
lilner:   ("lilit  es  ein  Iinpfcarcinom?     A.  f.  klin.  Chir.,  74  Bd.,  1004. 
Junzer;    Chorioepithelioma  malifinum.     Cbl.  f.  allp.  Path.,  xiii..  1002  (Lit."), 
roeggerath:  Beitr.  z.  Structur  u.  Entwickelung  des  Carcinonis,  Wiesbaden,  1S02. 
.  Notthaflft:   Ent.stehung  d.  Carcinonie.     Deut.  Arch.  f.  klin.  Med.,  54    Bd.,    180.5. 
'erez:   iiranchiogenes  Carcinom.     Beitr.  v.  Bruns,  2'.i  Bd.,   1800. 
i'etersen:  Beitr.  z.  Lehre  v.  Carcinom.     B.  v.  Bruns,  ;}2  Bd.,  1002. 
etersen  u.  Colmers:   Magen-  u.  Darmcarcinome.     B.  v.  Bruns.  4'.i  lid..  1001. 
blzl:   Krebs  einer  Dermoidcyste.     Cbl.  f.  allg.  Path.,  xv..  1004. 
^ibbert:   Das  pathologische  ^^'achstum,  Bonn,  180(1;    Geschwulstlehre,  Hoim    10(11. 
'.isel:   rel)er  ilas  maligne  Chorionepitheliom,  Leipzig.  1003  (Lit.). 
chimmelbusch:  Ueber    multiples    Auftreten    primiirer  Carcinome.     Langenbeck's 
'      Arch.,  40  Bd. 

{chmidt,  M.  B.:    Plexiformes  Epitheliom  derHaut  mithyaliner  Degeneration.    Beitr. 
J      V.  Zicjilor.  viii.,  18<)(). 

jChuchardt:  Beitriige  zur  Ent.stehung  der  Carcinome,  Leipzig,  188."). 
chiitz:   Mikroskopische  Carcinombefunde,  Frankfurt,  1800. 

chwalbe:  Carcinom  in  einer  tuberkulosen  Caverne.     Virch.  Arch.,  140  Bd.,  1807. 
now:  .\  Treati.se  on  Cancers  and  the  Cancer  Process,  London,  1803. 
ticker:  Carcinomliteratur,  Berlin,  100.'3. 
trbbe:    Histogenese  u.  Aetiologie  d.  Carcinonis.     Cbl.  f.  allg.  Path.,  ii.,  ISOI  (Lit); 

Cellulare  Vorgiinge  in  CJeschwulsten.     Beitr.  v.  Zif-gler,  xi..  1801. 
auflfer:   Carcinom.  Degeneration  von  Dermoidcysten.     Virch.  .Vrch.,  142  Hi!.,    1S'.».'). 
eacher:  On  Cliorioepitlielioma.     Journ.  of  Obstetr.,  ix.,  1003. 
hiersch:    Der  i:|)itlielkrebs.  namentl.  der  iiuss.  Haut,  18()0. 

illmanns:  .Vctiologie  u.  Histogenese  d.  Carcinonis.     Langenbeck's  .Vrch..  1..  1895. 
irchow:  Zur  Diagnose  u.  Prognose  des  Carcinonis.     Virch.  Arch.,  Ill  Bd..  18,S.S. 
I'^aldeyer:    Die  Ilntwickelung  der  Carcinome.     Virch.  Arch.,  41  ami  ")')  Bd.;   Samml. 

klin.  Vortr.  v.  Volkniann,  No.  33. 
[''illiams;  Chorioepithelioma.     Amer.  Journ.  of  Obst.,  1808  (Lit.). 
;amagiva:  Carcin.  Degen.  von  Dermoidcysten  d.  Ovariums.     Virch.  .Vrch.,  1  17  Bd., 

1S07. 
:ihn:  Beitr.  z.  Hi.stogenese  der  Carcinome.     Virch.  .Vrch.,  1 17  Bd.,  1889. 
j     Seeal.so  §§  121  and  123. 

i  (TnniiiKilic   Kjiilhrliitl   Ci/.sl.s.) 

bhn:  Traumati.sche  Ei)itlielcysten.     Virch.  .Virii..  144  Bd..  1807 

arre:    Tra  "    '''  "     *  "  "'     ' 

[aufmann 
Torz:  '1 


I  lauiiiji  ii.M-nc  r,|)ii  iit'R  y.'siiMi.       luiii.  .\iiii..  i  i-i  u-i.,  n-./f. 
Trauiiiat.  lOpitheicvsten.  d.  Finger.     lieitr.  v.  Brims,  xi.,  1804. 
mn:    Enkatarrhap'hie  v.  Epithel.     Virch.  Arch..  07  Bd..  I8.S4. 
■'"raumat.  Epithelcysten.     Beitr.  v.  Brims,  xviii.,  1807  (Lit.). 


I    §123.  Tlic  Structure  of  a  carcinoma  is  (irtcrniiiKMl   By   its  mi-ii 
|ie  manner  ill  wliicli  tlic  (•i)itli<diiiiii  prolifcialrs  iiimI  I  he  iissociaied  |.r 


468 


TUMORS. 


-H  in>  f  in  ♦'t  of  the  tmn-ue  (Mullers  fluid  hi'mitox\  Iin   eosin) 
U  itUeliil  ptails    /    sti  iiu  llXl 


5 

a  Fpithelial  plugs  w 


liferatioii  of  the  connective  tissue  make  it  possible  to  distinguish  a  ci- 
nective=tissue  stroma  which  contains  the  blood-vessels,  and  nests  ;d 

strands  of   cells— le 

-««5«s^'2:»-^C--;;---^*^^  i^o.called  cancer=pl.^s 

— which  lie  embed  fd 
in  the  stroma.  If  ^e 
cancer  grows  iutcja 
tissue  having  a  speM 
structure,  the  stnb 
may  contain  muse- 
tibres,  bone  trabecie, 
unchanged  glaudi;ir 
tissue,  etc. ;  but  tljSe 
tissues  usually  die  a  3r 
a  time.  In  geners  a 
carcinoma  possessef.m 
alveolar  structi'e, 
at  times  suggestiug'tu 
imperfectly  develo'id 
acinous  gland,  atoisr 
times  a  tubular  ghi;!, 
so  that  it  is  possibl  to 
distinguish  acinous  'id 
ti(bidar  types  of  c.n^i- 
noma.  When  the  (J- 
plugs  are  solid,  v,^- 
out  a  lumen,  the  growth  may  be  called  a  carcinoma  solidum  or  me  ly 
carcinoma.  The  presence  of  a  lumen  in  the  cell-plugs  gives  to  le 
growth  an  appearance  resembling  anatomically  the  adenomata,  id 
warrants  t lie  designation  carcinoma  adenomatosum  oradenocarcinoa. 
The  type  of  carcinoma  is  to  a  certain  degree  drp^ndent  upon  thepni  >f- 
ilssur  in  wliich  it  arises,  and  the  cells  may  still  show  the  characteri?  cs 


Fig.  342.— Carcinoma  of  the  skin,  with  delicate  cellulai 
network  and  area.s  of  hj-aline  connective  ti-ssue.  (Alcohol 
hccmatoxylin.)     x  80. 


\  AKii:rii;s  of  c  \ic(  i\(  )M  \, 


ii; 


of  the  parent  opitheliniu.  Squaiuons-ci'llcil  carcinoiii;!  iii;i\  he  cxprclrd 
to  occur  Avherevcr  lliciv  is  s(|uaiiu)us-c«-llr(l  cpitlicliiini,  and  cyliiulrical- 
celled  earcinoinata  in  nuicous  nuMnltraiics  having  (-ylindrical  cells, 
(.'ornification  takes  place  in  carcinoniata  of  tlie  skin,  mucoid  d«';,M'ncr:i- 
tion  in  those  of  mucous  nuMnbranes,  while  the  formation  of  colloid  occurs 
in  those  arisinj:;  from  the  thyroid.  l)ei)artures  froiji  this  rule  ar«',  how- 
ever, common,  in  that  the  t'i)itlu'lial  cells  may  lemain  at  a  less  liij^hly 
diirerentiatcd  sta.u'e,  s(»  that  the  tyi)e  of  the  cell-variety  coucenied  may 
not  be  developed  to  iti>  fullest;  or  it  may  happen  that  the  cells  lose  their 


v^  -X"*?   3B' 


Fig.  343.-  Adenocarcinoma  recti  tubulare  (alcohol,  aluiii-carininc).    <i,  /).  K|iitlii-lia_l  >,'laiiil-tubules ; 
c,  f],  stroma  ;  t/,  collections  of  leucocytes  in  the  ^liiiKl-tiitnilfs.      •  to. 


original  character  and  take  on  others.  For  examide,  colloid  like  sul> 
stances  may  be  formed  in  cancers  (d"  the  skin,  mucus  may  be  itrodiicn 
in  mannnary  cancels,  or  horny  s<(uaiiious-celled  carciiKtmala  may  <le\  rlo| 
in  nuicous  membiaiies  ]>ossessiii<;  cylindrical  epithelium  (<,^all-bladdci 
lor  in  those  haviiii;-  transitional  epithelium  (peh  is  ol"  kidney  ). 
I  (1)  5quamous-celled  cancers  develoj)  in  the  skin  and  in  lh<>>( 
'mucous    membranes    covered    with     squamous  cells.      They    occur. 


ivUv 


pha 


»l>ha;rus, 


ill  blad<lrr-..r   in   tin- 
-inainsof  t  ht-  bianehial 


illierefore,   in    the    external  skin,  moutl 

llarynx,  \ajiiiial  jxtrtion  of  the  cer\ix,  \a^iiia,  and  extnnal  genitals.      In 

hire  cases  they  may  develoj)  in  inucous  membranes  possess!  n;,M-\  lind  ileal 

ti'pithelium— for  exami)le,    in    the  trachea 

remains  of  ftetal  stiuctures — for  example, 

cleft.s,  and  in  deiinoids. 

The  flat-celled  cancer  is  chararterized  chielly  by  the  formation  of 
relatively  lar^e  cell-nests  (Fi^^s.  .'341,  a)  of  irre^Milar  shap«-;  but  they 
F)f ten  form  also  small  strands  of  cells.  The  e|»ithelial  cells  which  are 
polk'cted  in  masses  show  cleai'ly  tln'  cliaracter  of  slratilicd  xpianiuns 
I'pithelium  with  the  formation  of  prickle-cells,  ]»ut  <»n  accuunt  of  thrir 
jinidtiplication  within  the  tissue-s]»aces  ar<'  usu;\\\y  jKili/iiiDiitlnnis,  and  no 
Poii},'er  manifest  their  tyi)ical  characteristics.  \'ery  often  thr  formation 
|)f  keratohyalin  and  cornification  takes  jthn-e  within  tin*  lar;:«-  epithelial 
blugs  whicii  have  penetrated  into  the  deeper  tissues.  The  cells  wliich 
nave  undergone  a  horny  chan.u<'  becom.- anan^'ed   in  eune.-nlrir  lamina* 


470  TUMORS. 

resembling  those  of  an  onion  (Fig.  341,  a).  Such  cell -nests  are  known 
as  epithelial  pearls  or  Iwrny  bodies,  and  give  occasion  for  the  designation 
of  the  tumor  as  a  liornjj  eancer.     If,  instead  of  coruification,  the  central 


^f/^Z\'^'' 


Fig.  344.— Adenocarcinoma  fundi  uteri,     a,  Stroma;  b,  cancer-plugs ;  c,  isolated  cancer-cells.    X 


/^.^/ 

«■*"  *  «/?« 


'<^ 


Mr 


'^r^' 


nW    "^ 


Pig.  345.— Carcinoma  simplex  mammae  (alcoliol,  liaematoxvlin).     fr.  Stroma ;    b,  cancer-plugs ;  c,  Isolateii 
cancer-cells;  d,  blood-vessels;  e,  small-celled  inflltration  of  tlie  stroma.    X  200. 


VARIETIES    OF    C'AHCl.NO.MA.  171 

iportioiisof  the  cell-nests  undoriio  necrosis  :iii«l  li<|iicl:icli()ii,  llic  csirciimmn 
Imay  take  on  an  adenoma -1U«-  sti-netuiv. 

Besitles  tliese  tyjjical  ttat-celled  caneers  tlinc  often  occur  in.  tlic  skin 
and  nuu'ous  membranes  j-jossessing  squamous  cells  carcinomata  having 


'it 

'^$'.'^.: 

>:'''' 

•  ^  V-'*'i,\''.'] 

•*.  >"^-.  V«  '*' 

s:';','' 

'•.»/  •'°:-^.'  , 

jV'-'. 

•  :•, '  '.-^  •.;  • 

^y.' 

'  c' v.*-'I-H**!. 

•'••; ' 

'''./.'y'it'i-i^}'- 

v,';." 

Fig.  ;Ho."Aoinnus  carcinoma  of  the  mammary  frlaml  with  larire  nests  of  cells  (Miiller's 
lluid,  hipmatoxylin).     >'  Kdl. 

epithelium  persisting  at  a  lower  stage  of  development,  so  that  Die 
fcll-strands  remain  slender  and  delicate,  and  consist  of  small  e]>itlielial 
•ells  of  different  forms  (Fig.  342 )  that  do  not  change  into  i)rickle-cells 


«/«. 

M 

".•v 


I      Fig.  347.— TuDuiarscimious  cancer  01  tne  mammary  giana   iMuiiers  nuiu,  iia-iiiiuoxjriiu).    u.  Area 
ivlth  well-developed  elongated  nests  of  cells;  /<,  portion  of  tumor  in  whi(;h  the  cell-nest.s  have  for  the 
er  part  disappeared.     X  1(H). 


jrreate; 


ind  horny  cells.  Krompecher  designates  sucli  cancers  as  hasal-rrJlrd 
■arcinomata,  since  they  develop  from  the  layer  of  basal  cells.  Tlu^  cell- 
H)rds  of  these  carcinomata  are  nsually  solid,  but  through  the  production 


472 


TUMORS. 


of  hyaline  cell-products  in  the  centre  of  the  cell-masses  they  may  take  o; 
an  adenomatous  appearance.  ; 

(2)  Cynndrical=cened  carcinomata  develop  chiefly  in  those  niucov: 
membranes  possessing  cylindrical  epitlielinm — intestines,  stomach,  resp 
ratory  tract,  body  of  the  nterns,  and  gall-bladder,  but  occur  also  ii 
glands — ovary,  mammary  gland,  liver,  etc. — as  well  as  in  the  cerebrjj 
ventricles.  Such  tumors  exhibit,  at  least  in  the  early  stages  of  develo]J 
ment,  the  character  of  carcinoma  adenomatosum  or  adenocarcinoir 
(Figs.  336,  337,  343),  and  also  form  epithelial  structures  which  resembj 
glands  and  consist  of  variously  formed  gland  tubules  lined  by  a  simpj 
or  stratified  epithelium.  A  more  active  proliferation  of  the  epithelij 
cells  leads  finally  to  the  formation  of  compact  cell-nests  possessing  i' 
lumen  (Fig.  344).  i 

The  stroma  of  cylindrical -celled  carcinomata  is  usually  poorly  d' 
veloped;  and  the  tumor  consequently  bears  the  character  of  a  soft  ca. 
cer,  a  carcinoma  medullare.  Nevertheless  the  cancerous  tissue  may  i 
some  cases  j)ossess  a  hrm  consistence.  | 

(3)  The  carcinoma  simplex  or  carcinoma  in  the  narrower  sense — tbl 
is,  a  cancer  whose  especial  characteristics  are  derived  from  the  form  ai| 
position  of  the  cancer-cells,  in  that  these  are  arranged  simply  in  irregi 
lar,  compact  heaps  (carcinoma  solidum)— occurs  most  frequently  . 
glands,  but  may  develop  also  in  the  mucous  membranes  and  skin.  T|' 
cell-nests  are  in  j)art  very  irregularly  shaped  (Fig.  345),  in  part  rou j 
(Fig.  346),  or  in  other  cases  elongated  or  fusiform  (Fig.  347).  Th(« 
variations  liave  given  occasion  to  the  employment  of  the  terms  carcir!= 


Fig.  348.— Section  throug-h  a  segment  of  a  carcinoma  of  the  breast  (alcohol,  hiBmatoxylin).  o,  Niiej 
?),  tissue  of  gland;  c,  skin;  (/,  gland-ducts;  e.  carcinomatous  masses  occupying  the  place  of  the  fjiw 
tissue;  /,  carcinomatous  inQltration  of  fat  tissue;  (/,  portion  of  skin  inflltrated  with  carcinoma:  /i,  »* 
of  cancer-cells  in  the  nipple ;  i,  normal  gland-lobule ;  lu  small-celled  InUItratioa  of  the  connective  t  :ie. 
Jlagnifled  by  hand-lens. 


ma  acinosum  (Fig.   346)  and  carcinoma  tubulare  (Fig.  347)  as  diS|li- 
guishing  types  of  corresponding  character.     It  should  be  noted,  howe^r, 


VARIETIES    OF    C  A  KCI  NOMA. 


47:i 


ihat  these  different  types  may  be  juvsimiI   in  ilic  saint' iniiMir  (Fig. 

^,/,  (7),  since  the  eharaeler  of  the  cell-nesls  dcpeiuls  ])artly  upon 
;  manner  of  jiiowth  and  partly  npon  that  of  the  eoiiiiectivc-iissnc  si 
i  ill  whieh  tliey  develop.  At  the  seat  of  ori.<;in  of  the  tnmor  Ihc  cell 
I  may  have  a  variety  of  shapes  (e) ;  in  adipose  tissne  Ihcy  air  idu 
i(/);  in  the  nnyielding  connective  tissne  of  the  skin  they  aic  small 
I  fusiform  (//). 

I  An  abnndant  development,  of  cell-nesls  wilhin  a  (Itlicalc  ((Minrc 
'tissue  stroma  leads  to  the  formation  of  a  carcinoma  medullare 
marked  development  of  the  connective-tissue  stroma  with  llic  I'oiin: 

of  relatively  few  cancer-cells  oives  rise  to  a  hard  tumor,  Nvhich  is  c; 

a  carcinoma  durum  or  a  scirrhus  (Fig.  347). 


34S. 
their 
roma 
nests 
nded 
and 

tiv<'- 


^^  r 


>';f>:-^ 


'SSSSPS 


i.' 


tU 


:^'i 

.^  .-•? 


1  FiG.at'.t.— Mucoid  carpinoina  of  the  mammary  glami  (MiilU-r's  fluid,  lueiiiaU.x.vliii.  e..snii.  lU  Nniinal 
•Kland  tissue:  h,c.  earlv  stages  of  carcinomatous  imilifcratioii  with  bejrinninjr  formation  of  mucus:  <l, 
jlarKercell-nests  with  masses  of  mucus;  e, /,carcluouia  tissucshowiiiKuiarkcii  mucous  desjcneniilcn.    •  .«>. 

The  hard  variety  of  cancer  owes  its  origin  to  tlie  fa.t  that  thccrll- 
nestsare  from  the  beginnin*;-  relatively  few  and  small,  while  the  coiinec- 
ilive-tissne  stroma  is  abundant  and  hard.  Such  tumors  are  formed  espe 
•  iallywhcn  the  epithelial  proliferati.m  iiililtrates  into  hard  coimeet  i\  e 
'i>sne,  as,  for  example,  in  the  mammary  gland  and  skin,  Init  the  same 
«liaracteristics  may  be  exhibited  in  the  case  of  newly-formed  conueclixe 
tissue.  In  the  coiiise  of  time  a  cancel-  becomes  harder  l)y  icason  «»f  the 
destruction  of  a  large  port  ion  or  of  all  of  the  nests  of  epithelial  cells  (l-'ig. 
347,  h),  while  the  connective  tissiu^  increases  in  amount.  An  ttriginally 
isoft  cancer   may    become    hard    through   a   more  or  less  i»roiionnced 

inkage  of  the  cancerous  tissue  in  association  Mith  the  induration  of 


bhri 


474 


TUMORS. 


Fir,.  350— Karly  stages  of  development  of  a  mucoid  carcinoma  of  stomach,  arising  in  an  atroph 
mucosa  (formalin,  alcohol,  hsBmatoxylin,  eosin).  a,  mucosa;  h,  muscularis  mucosae;  c,  submucosa;  i 
muscularis;  c,  serosa;  /,  (/,  Mucoid  cancer.    X  9.  . 


the  tissue.  Carcinomata  of  the  iiuiminary  gland,  stomach,  and  intestii, 
veiy  often  show  such  secoudaiy  hardening,  and  in  cancer  which  has  ii' 
dergone  such  a  fibrous 

change    the    nests    of  ^  ; 

cancer-cells  may  be  en- 
tirely absent. 

(i)  The  chorion- 
carcinoma  or  malig= 
nant  chorio=epitheli= 
oma  is  distinguished 
from  other  carcinomata 
by  the  presence  in  the 
individual  cell-masses 
of  a  mixture  of  vari- 
ous cell-forms  (Fig. 
340,  a,b)  belonging  to 
the  ffjetal  ectoderm. 
Such  a  combination  is 
not  everywhere  pres- 
ent, and  does  not  occur 

('S])ecially  where  single  cells  or  cell-groups  penetrate  into  the  bid- 
stream  or  are  transported  passively.  The  conditions  favoring  a.  ?■ 
velopment  within  the  blood-vessels  are  found  when  fluid  and  ccji  i- 
lated  masses  of  blood  lie  between  the  tumor-cells  (c). 

(,"))  Cancers  characterized  by  peculiar  secondary  changes  aie 
through  the  formation  of  especial  i)roducts  l)y  the  cancer  cells,  orthro>jlj 
peculiar  metamorphoses  of  the  same,  or  more  rarely  througli  changelS 
t*he  stroma.  j 

Mucoid  or  gelatinous  cancer — carcinoma  mucosum  (C.  f/ehdinosfk 
C.  coUokles) — is  that  form  of  carcinoma  in  which  the  epithelial  cells  ]fi: 
duce  mucus  (mucin  or  pseudomuciu)  or  a  more  colloid-like  gelatiiijiS  i 
substance.     Such  production  of  mucus  occurs  particularly  iu  cancerjrf 


Fig.  3.")1.— Carcinoma  mucosum  mammae    (alcohol,  hiematoxy. 
«,  Stroma;  />,  cancer-plu.trs ;  c,  alveoli  without  caucer-cells :  <h 
containing  spherules  of  mucus.    X  200. 


fl 


VAHIKTIES    OF    CAIUIXOMA. 


475 


.Ulwii.l  (^Fi.u-.  ni!)j;    and 


c 


drops   witliln 


Fig.  352.— CarciiKiuia  uiili  liyuli 
tbe  ccll-ncsts  (('aniiKiiiia  (■vlindroiiiatosiiiii).  o.  Cell- 
nest  witliout :  /),  cell-iicst  with  a  few  hyaline  spher- 
ules; c,  cells  wliieh  have  been  reduced  to  strands  ar- 
ranged in  a  network,  as  the  result  of  the  fornialion 
of  numerous  hyaline  spherules.    X  150. 


(Fif;.   3.-) I,  (1),  and   hccoiiu's 
through  the  complete  destiuc- 


jie  intestine,  stomach  (Fig.  :>r)0),  and  man 

jay  be  manifest   in  the  earliest 

inges  of  the  development  of  the 

!imor(Figs.  840,  />,  <■:    3.")0, /,  r/), 

j.  that  the  mucoid  ])roducts  of  the  ^ 

i-lls  collect   first  in  the  centre  of  /■. 

'le  eell-nesls  after  the  manner  of  ^;| 

;  gland-secretion.     Later   the  \ 

)rder  of  cells  surrounding  the 
ncoid  material  is  broken 
rough,  the  cells  pushed  aside, 
parated    from    the    underlying  ), 

anictures,    and    crowded  toward  ;^.^ 

le  centre  of  the  mucus  contain-      q  -'-  ° i 
\^  alveolus  (Fig.    340,  d   r,    f).  ^>- 

jltimately,    the    epithelial   cells 
^e  wholly  destroyed. 
I  In  intestinal  cancers  the  for- 
mation of  mucin  takes  place  in 
jiblet-cells,  which  are  similar  to 
\e  goblet-cells  occurring   under 
l)rnial  conditions.     In  cancer  of 
(e  l)reast  the  mucus  appears  in 
|e  form  of  droplets  within  the  cancer-ce 
|ee  either  by  escaping  from  the  cell,  or 
()n  of  the  cell  itself. 
{  Through  the  development  of  mucoid  or  colloid-like  masses  within  the 
jncer-cell  nests,  the  latter  may  become  studded  with  liyaline  drops,  and 
^ereby  acquire  a  mesh-like  appearance  (Fig.   3.")2). 
\'ve  formerly  designated  as 
ijiiidromata,     and     classified  i 

ith  the  corresponding  sar- 
«[inata.  Should  it  l)e  thought 
«sirable  to  retain  this  uo- 
jt'iiclature,  such  a  tumor  may 
I  designated  carcinoma  cyJin- 
iomatomm;  but  it  seems  un- 
ieessary  to  separate  these 
?owths  from  the  mucoid  and 
•Jlloid  carclnomata. 
j  When  the  cancer-cells  at- 
lin  an  extraordinarily  laige 
•T-e,  as  occurs,  for  example, 
\  tlat-celled  cancers  or  in 
jiicers  of  the  breast,  the  tu- 
^|I•  may  be:  termed  a  carci= 

i>ma  gigantocellulare.  If  the  enlargement  of  tin-  cells  is  n«.t  due  to 
:  increase  in  the  amount  of  i)rotoi»lasm,  but  to  a  swollen  (-ondition  of 
te  cells  or  to  a  collection  of  drops  of  lliiid  in  the  cells  and  tlieir  nuclei 
fig.  3.").3),  the  cells  arc;  designated  j>////.sY///f/r.s-  (cdrcitioiiKi  jt/ii/sti/i/niiin). 
I  Myxomatous  defeneration  of  the  connective-tissue  stroma  may  occur  in 
frtions  of  a  cancer,  so  that  tlie  cancer-cells  become  separatecl  from  <'ach 
<Sier  by  myxomatous  tissue  (Fig.  354,  r).  Such  grow  t  lis  may  be  calliMl 
(rcinoma  myxomatosum. 


Such   formations 


Fifj.  :t.'):i— Knlarged  hydropic  cancer-cells 
cinoina  of  the  inannna  (Miiller's  tluid,  Bisiiiarrk-hrowii). 
(/,  ordinary  cancer-ccHls;  /).  hydropic  cells  contiiinliijrdmps 
of  till  id ;  c,  swollen  nucleus;  d,  swollen  nucleolus;  «■, 
wunderinp  cells.     ,•   ;j(K). 


476 


TUMORS. 


Hyaline  degeneration  of  the  connective  tissue  occurs  in  differe 
forms  of  cancer,  l)ut  is  nsnally  confined  to  small  areas  of  the  tumor. 


i^ 


Fig.  354.— Carcinoma  myxomatodes  ventriculi  (Muller's  fluid,  hnematoxylinK  a.  Cancer-plugs  p, 
connective-tissue  stroma ;  c,  stroma  of  myxomatous  tissue ;  rf,  cancer-cells  which  have  undergone  mu  is 
degeneration.    X  2tX). 

Deposits  of  lime=salts  in  carcinomata  occur  chiefly  as  concretiou-lje 
masses,  similar  to  those  found  in  i^sammomata.  The  concretions  iiiy 
form  either  from  the  cells  or  in  the  connective  tissue.  They  are  obserJd 
particularly  in  papillary  adenomata  and  carcinomata  of  the  ovary,  id 
in  cancers  of  the  mammary  gland.  There  also  occur  more  extensive  jl- 
cifications,  ^vhich  may  lead  to  complete  petrifaction  ;  and  tumors  shv- 
ing  such  changes  occur  chietlv  iu  the  skin  and  subcutaneous  tissue.'^  ii 


Fig.  355.— Adenosarcoma  malignum  of  the  kidney,  from  a  child  seven  j^ears  of  age  (formalin,  htemat  >"iin, 
eosin).    a.  Tissue  with  gland-tubules ;  ^,  sarcoma-like  tissue.    X  300. 

the  form  of   sharply  defined,   hard,   rounded   nodules.     Some  of   ^ 


VARIETIES    OF    CAHCI  NOMA.  477 

iiuors,  lU't'onlinji- to  the  descriptions  jj;iveii,  are  to  bo  classod  with  the 
iroinomata,  others  represent  calcifiod  atberomata  or  adenomata  of  tlu- 
^baoeous  elands. 

If,  at  the  same  time  with  development  of  the  epithelial  iie\v-«rrowth, 
lere  occnis  a  marked  proliferation  of  the  connective  tissne,  leading,-  to 
le  formation  of  a  very  cellular  tissue,  there  arise  liiinors  wiiicii,  a«'C(»i(l- 
,!<;  to  their  structure,  nmybe  designated  adenosarcomaor  sarcocarcino- 
!ia.  Typical  examples  of  this  form  of  tumor  occur  in  the  kidneys  (  I"'i<i. 
j>5,  a,  b),  forming  medullary  tunuM's,  the  orioin  of  Avhich  is  ])r(»l)al»ly  to 
?  referred  to  a  disturbance  of  development  of  the  kidney.  Such  tumors 
ay  show  a  varying-  structure  in  different  parts,  at  one  time  more  of  an 
ienomatous  or  carcinomatous  character,  at  another  time  only  a  siirco- 
atous.     The  metastases  of  such  tumors  exhibit  a  similar  character. 

Spontaneous  healing  of  carcinomata  does  not  take  place,  but  many  of  them 
•jw  very  slowly,  and  many  processes  within  cancers  may  be  interpreteil  as  local 
umpts  at  ficali'i'j.  In  this  category  lielong  especially  the  degenerative  jirocesses  in 
e  cancer-cells  that  lead  to  their  death  and  dissolution,  so  that  finalh'  in  large  areas 
«the  neoplasm  (for  example,  in  cancer  of  the  stomach)  there  may  be  fountl  only  hyper- 
jistic  masses  of  connective  tissue,  but  no  more  cancer-cells.  It  is  verj' probable'"  that 
i  the  destruction  of  the  cells  proteolytic  ferments  may  play  a  role.  Tlie  occurrence  of 
ilcification  in  a  cancer  depends  upon  a  previous  death  of  its  cells.  Further,  the  fact 
ut  transported  cancer-cells  (compare  §  125)  do  not  always  give  rise  to  daughtcr- 
^lors,  but  very  frequently  die  at  the  place  where  they  lodge,  may  be  interpreted 
II  a  healing  process. 

:  Various  authors  (Becker,  Petcrsoi,  Schrrarz,  Orth)  would  also  look  upon  the  occur- 
iiice  of  giant-cells  within  tumors  as  a  process  of  healing;  it  would  be  more  correct, 
Iwever,  to  say  that  in  the  course  of  certain  retrograde  processes  giant-cells  may 
:!pear.  The  cause  of  the  retrogression  lies  not  in  the  giant-cells;  tliey  a|)pear  only 
itier  certain  conditions,  and  especially  when  in  cancers  corpuscular  elements  of  cer- 

n  kinds,  cornified  cells  in  particular,  come  in  contact  with  connective  tissue.     They 
nothing  more  than  foreign-body  giant-cells,  and  their  occurrence  is  to  be  regarded 

y  as  secondary  to  certain  retrograde  processes. 


Literature. 

{Anaiomy  of  Carrinoma.) 

Icher;  Riesenzellenbildung  in  Krankroiden.     Virch.  Arch.,  156  Bd.,  1S90. 
Ineke:   Carcinom.     Bibl.  d.  med.  AViss.  v.  Drasche,  Wien,  1900. 
1-ch-Hirschfeld:  Kmbn-onales  Adenosarkom  der  Niere.     Beitr.  v.  Ziegler,   xxiv., 
•    IS'JS. 

Irrmann:   Z.  Frage  d.  Spontanheilung  des  Krebses.     D.  med.  Woch.,  1004. 
Cilesotti:  ("arcinomes  calcifies  de  la  peau.     Rev.  med.  de  la  Suisse  rom.,  I'tO-J. 
I'hler:  Carcinome  bei  Pferden.     Z.  f.  Tiermed..  v.,  1901. 
last:    Verhornender   Plattenepithelkrebs   des  Bronchus.      Beitr.    v.   Ziegler,   xx., 

I.edlander:  Geschwulste  mit  hyaliner  Degeneration.     Virch.  Arch.,  G7  Bd.,  lS7(i 
Cieser:    riitcrsucii.  fiber  d.  Ch()lesteatom.     \'irch.  .\rch.,  122  BtL,  1S90. 
Insemann:  Stclkmg  d.  Adenoma  malignum.     Virch.  Arch.,  Kil  Bd..  HtOO. 
vKosinski:  Schleimmetamorphose  der  Krebszellen.     Ch\.  f.  allg.  Patli.,  iii.,  1S92. 
^ster:   Kankroid  mit  hyaliner  Degeneration.     Virch.  Arch.,  40  Bd.,  ISC)?. 
Itampecher:  Der  drusenartige  Oberflachenepithelkrel)s.     Beitr.  v.   Ziegler,  xxviii., 

\'.m. 

Inge:  Der  C.allertkrebs  der  Brustdriise.     Beitr.  v.  Bruns,  xvi.,  l.S9(i. 

liser:  Verkalkte  Epitheliome.     Beitr.  v.  Bruns,  xxvi.,  1900. 

lamer:  Wachsthum  d.  Haut-  u.  Schleimhautcarcinouie.     Beiti.  v.  Zicgl.r,  xxvm., 

19(J0. 
Mherbe:   L'ejjitheliome  calcific.     Arch,  de  phys.,   1881;    Kech.  s.  rei)itlirl.  calcific, 

I'nris,  ]NS2. 


478 


TUMORS. 


Neugebauer:   Psammoses  Carcinom   der  Brustdriise.     Arch.   f.   klin.   Chir.,  48  Bd 

1894. 
V.  Noorden:   Das  verkalkte  Epitheliom.     Beitr.  v.  Brims,  iii.,  1888. 
Olivier:  Cancer  du  sein  avec  corps  calcaires.     Beitr.  v.  Ziegler,  xvii..  1895. 
Orth:   Heilun<rsvorganse  an  Epitheliomen.     Z.  f.  Krebsforsch.,  i.,  1904. 
Petersen:   Heilungsvorgange  im  Carcinom.     B.  v.  Bruns.  34  Bd.,  1902. 
Schwalbe:   Eisen  in  Carcinomzellen.     Cbl.  f.  a.  P.,  xii..  1901.  I 

Schwarz:   Epithelioma  papillare.     V.  A..  175  Bd..  1904.  : 

Selberg:   Das  maligne  Adenom.     Virch.  Arch..  160  Bd.,  1900.  ! 

Stieda:   Das  verkalkte  Epitheliom.     Beitr.  v.  Bruns,  xv.,  1896  (Lit.);  Psammocarcmo' 

d.  I'tenis.     Arb.  a.  d.  p.  I.  in  Posen.  her.  v.  Lubarsch,  1902. 
Wilms:   Mischgeschwiilste  der  Niere,  Leipzig,  1899. 

See  also  §§122  and  124.  j 

i 
§  124.  The  cystocarcinomata  represent  a  form  of  tumor  whi.i 
stands  in  the  same  rehition  to  cancer  as  the  cystadenomata  do  to  the  ad, 
nomata.  The  majority  of  cancers  form  no  demonstrable  secretion,  b', 
there  occur  certain  varieties,  particularly  in  the  group  of  adenocarcii 
mata,  in  which  the  epithelial  cells  produce  mucus  or  colloid  (thyroiti 
and  in  adenocarciuomata  of  the  liver  a  secretion  of  bile  has  been  observl 
(Schmidt).  In  cystocarcinomata  the  mucous  secretion  of  the  epithelh.'i 
may  lead  to  the  formation  of  large  spaces  filled  with  fluid.  Cystocar  - 
nomata  occur  chiefly  in  the  ovary  and  mammary  gland,  usually  beari^ 
the  character  of  a  cystocarcinoma  papilliferum  (Fig,  35o ),  in  that  ^3 
cyst-spaces,  in  certain  parts  or  throughout,  are  either  partially  (&,  c)  r 
wholly   (d,  e)  filled  with  papillary  proliferations.     These  excresceu-K 


Fig.  3.T6.~Cystocarcinoma  papilliferum  manim*.  ((.Stroma;  b,  smooth-walled  cysts ;  <"•  ^^y^jMn- 
taining  papillary  proliferations;  <?,  cvsts  entirely  fllled  with  papillary  proliferations;  e,  small,  ei^K^ 
papillary  growths;  /,  adenomatous  proliferations;  »,  papilla  of  the  mamma.    Reduced  about  one-th,. 


possess  a  soft,  medullary  appearance,  and  Miien  developed  in  great  im- 
bers  give  to  the  entire  tumoi-  a  marrow-like  character.  j  _ 

Both  the  cyst-wall  and  the  papillary  proliferations,  which  bran>in 
the  same  manner  as  do  those  of  the  papillary  cystadenomata,  are  co-red 
with  a  thick,  stratified  layer  of  epithelium   (Fig.  357,  />,  c,  d:  35,  <?). 


VARIETIES    OF    CAIU'IXOMA. 


479 


^le  papillte  are  usually  slender  (Fij;.  357,  c,  d),  but  throiij,'!.  v,,,.n,mafous 
iegencrafion  of  their  connective  tissue  may  attain  a  huge  size  (Fig.  :\r>^. 


K. 


FlG.357.-Cystocarcinoiiia  papilliferum  ovarii  (Muller's  fluid,  hiematoxyliuK    o.  Stroma  ;  />,  rpithelUim  ; 
c.  (f,  papllhe.     X  72. 

).  Through  total  myxomatous  def/enemtion  of  the  connrciirr  tissue  of  tlie 
apillte  the  latter  may  ultimately  become  converted  into  m neons  ei/sfssuv- 
ounded  by  epithelium.     If  at  the  same  time  the  epithelial  layers  of 


Fig.  STjS— Papillary  cystooarcinoma  of  the  mamma  with  papilla?  which  have  und»'r(ronfi  myxomaUiiw 
generation  (Miill«r's  fluid,  luematoxvlin,  eosini.  ri,  DiMisi-  loniK-rtivt-  tissui-;  I>,  inyxniimtinis  papllhr: 
pntllferatinjr  epithflluui,  arranped  in  sevi-ral  laycix.     .    73. 

eighboring  papilla?  become  confluent,  llic  ciiitlifliiini  linally  <m|im-<  t.. 
ppresent  a  stroma  which  incloses  balls  (.f  imicns. 


480 


TUMORS. 


The  metastases  of  cystocarcinomata  may  liave  the  character  of  caul  | 
flower-like,  papillary  growths,  and  this  is  particularly  the  case  whej 
ovarian  tumoi'S  of  this  nature  spread  throughout  the  peritoneal  cavit"! 
Other  metastases  show  the  characteristics  of  ordinary  carciuomata.       *i 

Literature. 

(  Cystocarcinoma. ) 

I 
Baumgarten:  Ovarialkystom  mit  Metastasen.     Vircli.  Arch.,  97  Bd.,  1884.  i 

Billroth:  llaiulb.  d.  Fraueiikrankheiten,  ii.,  Stuttgart,  1886.  j 

Leser:  Zur  patliol.  Anat.  d.  Geschwillste  der  Brustdrusen.     Beitr.  v.  Ziegler,  ii.,  18f. 
Pfannenstiel :  Papillare  Geschwiilste  des  Eierstocks.     Arch.  f.  Gyn.,  48  Bd.,  1895. 
Sasse:  C'ystische  Tumoren  d.  Mamma.     Langenbcck's  Arch.,  54  Bd.,  1897. 
Sciiinidt:  Becretionsvorgauge  in  Krebsen.     Virch.  Arch.,  148  Bd.,  1897  (Lit.). 
Stratz:  Die  Geschwillste  des  Eierstocks,  Berlin,  1894. 
See  also  §  122, 

§  125.  Growth  by  infiltration  and  the  involvement  of  the  surrounj- 
ing  tissues  takes  place,  during  the  early  stages  of  development  (Sec.  12' 
through  the  penetration  of  the  epithelial  elements  alone  into  the  uei^l- 
boring  tissue  in  the  form  of  connected  plugs  or  cords  of  cells.  5}t 
infrequently  there  appear  in  the  tissue-spaces  single  epithelial  cells  tilt 


I 


if 


Fig.  ;}59.— CoUoirt-containing  cancer  of  thyroid  inffltratino:   the  thyroid  cartilage  (alcohol,  h;i'iiiat<  lUn, 
eosln).    rt.  Cartilage;  h,  cancer-tissue  ;  f,  roIUiid  ;  r^  cancer-tissue  growing  into  the  cartilage.    ><:•• 

multiply  and  form  strands  or  round  masses  of  cells.  In  the  growth  if  a 
tumor  into  neigliboring  organs,  the  connective-tissue  stroma  (Fig.  35ijd) 
surrounding  the  cell-nests  breaks  into  the  neighboring  tissue  (a)  aii'fc- 
places  it.  Such  a  mode  of  infiltration  occurs  to  the  most  marked  depee 
in  the  case  of  carcinomatous  infiltration  of  cartilage  (a)  and  bones,  i 
Tiie  formation  of  metastases,  which  takes  place  more  frequent  in 


METASTASIS    OF    CAK'C  I\(»MA, 


481 


he  ca-se  of  carcinoma  than  anyotlici-  form  of  lumor,  is  \]w  natural  result 
)f  its  infill lat JVC  mode  of  .uiowlii.  In  Hi,,  piccess  of  inlillration  the 
viurr-rr/ls  hrrdi:  iiifoi/K'  li/nip/i-vf.s.scls  iV']'^.  'J  11).  and  thronuh  these  ai-e 
•arriedto  the  lymph-iilands.  In  both  places  tlieic  r«'sidts  a  mnlli|»lica- 
iou  of  the  transported  cancer-cells  (Figs.  244,  a ;  3G0,  d).  Jn  the  Ivmph- 
jlands  the  lymphadenoid  tissue  becomes  replaced  by  <-ancer  tissue;  the 
ymphocytes  vanish,  while  the  connective  tissue  of  the  lymph  inland 
^rves  as  a  framework  for  the  cancer. 

The  development  of  cancer  in  the  lymph-channels  is  either  limited  to 
he  tilling  and  distention  of  the  lymph- vessels  by  the  cancer-cells  (Fig. 
;44)  or  it  may  likewise  lead  to  the  formation  in  this  situation  of  daugh- 
er-nodules. 

The  epithelial  obstruction  of  the  lym])h-vessels  is  often  very  exten- 
;ive;  and  through  the  blocking-up  of  individual  lymi)h-channels  or  of 
Ihe  thoracic  duct  itself,  a  retrograde  7neta,sfasi.s  of  raneer-eells  may  he  camrd. 
I^r  example,  in  the  case  of  a  cancer  of  the  sto'mach  the  lymjih- vessels  of 
[lie  mesentery  and  the  thoracic  duct,  and  those  of  the  lungs,  or  even  of  the 
Ripper  extremities,  may  become  the  seat  of  metastatic  growths.  Thidugh 
lie  tlioracic  duct  cancer-cells  may  be  carried  into  the  blood-stream. 

The  ejnt/iilldl prolifcnifion  breaks  into  tilootl-n .ssds  not  less  frtMpn'utly 
han  into  the  lymi>hatics;  and  the  invasion  of  the  \eins  by  cancer-cells 
s  to  be  regarded  as  a  constant  phenomenon.  In  consequence  the  vessel- 
umen  l:)ecomes  tilled  with  cancer-cells,  and  at  a  later  stage  the  atlected 
)ortion  of  the  vessel  becomes  converted  into  cancer-tissue,  the  frame- 
work of  which  is  formed  through  the  proliferation  of  the  constituents  of 
he  more  or  less  altei'ed  vessel-wall. 


» 


Pio.  3fiO.— Section  from  an  enlarged  axillary  gland,  with  beginning  development  of  oanrer  (alcohol, 
!»matoxylln).    «,  (;enn-<entre  of  a  lymph-node;    />,  ivnipli-sinuses ;    »•,  artery;   »»,  nt-sts  of  oanf«T-<-elU. 


I     If  cancel -cell^ 
irculation  there 
31 


pass  from  the  thoracic  duct  or   fioi 

an-  fonne(l    lidiiKitiKiriioiix    nn  tdstdsi  s. 


in    into   the 
ircinoina  of 


482  TUMORSo 

the  stomach  and  intestine  cancer-cells  are  very  often  carried  through  tli. 
portal  vein  into  the  liver  (Fig.  245,  h,  c).  The  thoracic  duct  and  tin 
systemic  veins  permit  a  transportation  of  cancer-cells  to  the  lungs.  Ac 
cording  to  investigations  byM.  B.  Schmidt,  the  lungs  are  very  frequent!; 
the  seat  of  metastases,  but  iu  many  cases  these  do  not  develop  into  nod 
ules  visible  macroscopically.  Much  more  frequently  only  microscopi. 
iutra-arterial  groups  of  cancer-cells  embedded  in  thrombi  are  found,  .'j 
part  of  these  metastases  can  through  the  proliferation  of  the  tumor-cell' 
develoj)  into  daughter-nodules,  and  the  lungs  may  contain  numbers  o 
these.  Very  often,  however,  the  transported  cells  fail  to  develop  iut 
cancer-nodules  (Schmidt).      The  transx)orted  cells,  that  perhaps  have  r( 


IC 


i^'j 


y 


Fig.  361.— Metastatic  collection  of  young  cancer-cells  within  a  liver-capillary,  arising  from  a  prin  V 
adenocarcinoma  of  the  stomach  (alcohol,  hajmatoxylin).    X  300. 

Fig.  362.— Metastatic  development  of  cancer  within  the  liver-capillaries,  arising  from  a  primary  en - 
noma  of  the  pancreas  (alcohol,  carmine) .  Both  connective  tissue  and  nests  of  carcinoma  cells  have  ■- 
veloped  within  the  capillaries.    X  250.  ! 

I 

cently  proliferated,  die,  and  there  occurs  only  a  proliferation  of  connj- 
five  tissue  in  the  vessel-wall,  leading  to  the  organization  of  the  thrombi. 
In  other  cases  the  cancer-cells  increase  within  the  vessel-lumen  with' t 
forming  large  nodules.  ; 

When  cancer-cells  enter  the  systemic  circulation  there  occurs  a  distrilmtui 
of  the  carcinoma  to  the  various  organs.  It  is  not  yet  known  to  what  ext'jt 
the  transported  cells  die.  The  favorite  seats  of  secondary  developnijt 
of  cancer  are  the  bones,  liver,  and  kidneys.  Occasionally  a  developm,it 
of  carcinoma  may  take  place  in  all  the  organs  of  the  body,  so  that  jC 
resulting  condition  may  be  styled  a  general  carcinomatosis.  ] 

The  secondary  cancer-foci  develop  first  intravascularly  (Figs.  361,  3^, 
and  363,  e).  In  the  beginning  the  neighboring  tissues  are  but  li|e 
changed  (Fig.  363).  Later  there  occur  in  part  tissue-degenerations  (Jp 
363,  /)  and  in  part  connective-tissue  proliferations  (Figs.  362,  364,  c,  h 
and  the  newly  formetl  connective  tissue  serves  as  the  stroma  for  tbeip- 
vel<)])ing  cancer-nodule.  The  amount  of  this  connective  tissue  va.es 
gi-eatly,  and  is  de]i(Mident  in  part  upon  the  parent-tissue  iu  which  le 
tumor  develops  and  in  x)art  upon  the  variety  of  cancer.     The  r«t 


(AHCIXO.MA. 


•^ 


483 


Fig.  363. — Carcinomatous  metastases  in  the 
arcinomatos's  following  carcinoma  of  the  man 
Iiiscularis  of  the  uterus;  6,  normal  mucosa;  c. 
itt-rine  glands;  d,  upper  layer  of  the  mucosa  densi 
Ipithelium;  /,  ulcerated  area.  (Blood-clots  con 
i.  100. 


iliii,    li 

Uil'h'  Ul 


111'  inuco.sa,  in  uiiiver.sal 
;iloN.vlin  and  eosin.)  a, 
\\\r  vessels  between  the 
ol  (  ancer-cells;  c,  uterine 
e  found   in  the   uterus.) 


v^^'^^^^- 


%. 


m 


9"^: 


-S 


Ok 


i  Fig.  364.— Metastatic  development  of  cancer  ill  the  diploii  of  the  .skull-cai)  in  primary  car- 
noma  of  the  stomach.  (Formalin,  ha-matoxvlin.  eosin. >  a.  Marrow-tissue:  h,  nest  of  rancer- 
4,j  '^'  proliferated  endosteum  with  nests  of  cancer-cells;    d,  fully  developed  area  of  carcinoma. 


484  TUMORS. 

marked  comiectiye-tissue  proliferation  occurs  in  the  cancer- metastas< 
in  bones  (Fig.  364),  particularly  Avben  there  is  a  diffuse  growth  of  tl; 
carcinoma  through  the  bone.  With  the  destruction  of  the  old  boue  tl! 
carcinoma  may  form  in  phice  of  the  bone-substance  au  abundant  tibroii 
stroma  in  which  osteoid  tissue  or  new  bone  may  be  formed  in  lar^j 
amounts.  It  would  appear  that  many  carcinonmta  must  produce  suj 
stances  that  excite  a  marked  proliferation  of  the  periosteum  and  endoj 
teum.  Similar  marked  proliferations  may  occasionally  be  observe' 
when  carcinomata  sjDread  over  the  serous  membranes,  j^articularly  t]\ 
periosteum.  i 

As  has  already  been  mentioned  in  §  101,  carcinomata  may  be  tranj 
planted  to  individuals  of  the  same  species,  and  after  operations  irj 
plantation=carcinomata  may  develop.  i 

Recurrences  after  the  removal  of  the  tumor  by  operation  are  vef 
common  in  the  case  of  cancers,  and  in  advanced  cases  can  scarcely  ;•, 
avoided.  They  arise  usually  from  remains  of  the  primary  tumor  or  fr(|i 
metastases  already  present  in  the  body  either  in  the  immediate  neigh- 
borhood or  in  distant  organs.  In  rare  cases  the  conditions  favoring  tj; 
growth  of  the  cancer  may  again  arise  in  the  neighborhood  of  the  svc 
resulting  from  the  operation,  so  that  after  several  years  a  neiv  cmiif 
develops.  i 

Recurrences  and  metastases  of  the  chorionic  carcinomata  grow  extrerrjjr 
rapidly  so  that  within  a  few  days  tumors  of  considerable  size  may  be  formed,  'ie 
dark-red  color  shows  even  to  the  naked  eye  that  blood  is  largely  concerned  in  tlfr 
make-up,  and  the  microscopical  examination  shows  that  the  rapid  increase  in  size  ijn 
a  large  measure  due  to  the  large  hemorrhages  caused  by  the  development  of  the  tun.'r. 
The  epithelial  masses  may  form  a  relatively  small  part  of  the  entire  bulk  of  the  gro\|i. 

Chorion  carcinomata,  that  is,  the  epithelial  cell-masses  characteristic  of  these  tumjs, 
have  been  repeatedly  observed  ouside  of  the  uterus,  in  various  organs  {Schmauch,  Schntl, 
Risel,  Busse,  Zagorjanski-Kissel),  also  in  cardiac  thrombi  (Busse),  without  any  tumcpf 
the  uterus  having  been  demonstrable.  This  phenomenon  may  be  explained  by  the  l3t 
that  the  epithelial  cells  of  the  normal  chorion  or  of  the  hydatid  mole,  that  is,  of  myxcja- 
tous  chorionic  villi,  may  be  transported  through  the  blood-stream  and  prolifete 
without  the  development  of  a  tumor  at  the  placental  site.  j 

Literature. 

(Metastasis  of  Cancer.)  I 

Busse:  Chorionepitheliome  ausserhalb  der  Placentarstellen.     V.  A.,  174  Bd.,  190^: 
Cuneo-   De  I'envahiss.  du  syst.  lymph,  dans  le  cancer  de  I'estomac,  Paris,  1900. 
Dagonet:  Transmissibilite  du  cancer.     A.  de  med.  exp.,  1904. 
Ely.   A  Study  of  Metastat.  Carcinoma  of  the  Stomach.     Am.  Journ.  of  the  Med.  c, 

1890. 
Gierke:  Knochentumoren  mit  Schilddrusenbau.     V.  A.,  170  Bd.,  1902. 
Goldmann:  Verbreitungswege  bosartiger  Geschwiilste.     Beitr.  v.  Bruns,  xviii.,    W. 
Gussenbauer-  v.  Langenbeck's  Arch.,  14  Bd.,  1872. 

Hanau:    Erfolgreiche  Uebertragung  von  Carcinom.     Fortschr  d   Med.,  vii.,  1889< 
Jensen:   Exper.   Unters    fiber  Krebs  bei  Mausen    (Uebertragung   19  Generatjen 

hindurch),     Cbl.  f   Bakt.,  xxxiv.,  1903.  Orig.  I 

V.  Kahlden:  Carcinomrezidive.     Arch.  f.  klm.  Chir.,  68  Bd..  1902.  i 

Krukenberg:  Metast  Carcinom  d.  Chorioidea.  Mon.  f.  Augenheilk.,  Beilh.,  jOS. 
Milner:    Impfcarcinome.     A.  t.  klin.  Chir.,  74  Bd.,   1904.  j 

Risel:   Ueber  das  maligne  Chorionepitheliom,  Leipzig,    1903.  ' 

Schmauch:  Syncytioma  vaginale,     Z.  f.  Gebh.,  49  Bd.,  1903. 
Stiles.    Dissem.  of  Cancer  of  the  Breast.     Brit.  Med.  Journ.,  i.,  1899. 
Wehr:    Carcinomimpfungen  von  Hund  zu  Hund      Langenbeck's  Arch.,  39  Bd.,  '>89- 
Zehnder:   Ueber  Krebsentwickelung  in  Lymphdri'isen      Virch.  Arch.,  119  Bd.,  ];W. 

See  also  §  101.  I 


TKliATOII)     TiMOHS    AND    CVS  IS.  485 


3.  TiiK  TKKATmn  Timors  and  Cysts. 

1  §  1lH>.  I'nder  the  lieatl  of  teratoid  tumors  and  cysts  may  Ix-  uKiupiil 
ihose  tumor-like  formations  Avliieh  are  cliaracteiizcd  by  t ho  lad  lliat  llio 
issue-formations  of  Avhich  tliey  are  composed  oil licr  th)  not  ocnir  nor- 
nally  at  the  site  in  question  {hdcrotopous  (jron-th),  oi-  at  h'ast  «h>  not  nor- 
nally  appear  there  at  the  time  at  Avhieh  they  are  found  {hrtrnu-lninunix 
iivirfli).  Pa  it  of  the  teratoid  tumors  and  eysts,  Mhich  aie  classed  as 
:eratomata  in  tlie  narrower  sense,  exhibit,  inoreo\er,  tiie  i>eciiliarity 
I  hat  tiiey  ai-e  composed  of  a  varirty  of  f  issues. 

j  The  teratoid  tumors  and  cysts  may  be  conveniently  divided,  accordin;; 
lO  their  structure  and  their  orijiin,  into  tliree  j;roui)s,  as  folh.ws:  (1) 
The  si)iiplr  tcriitoid  tiniiors ;  (2)  f/ir  simple  teratoid  ejf.sts  :  (.■>)  the  compter 
\cratom((fa,  irhieJi  in  jxiii  contain  tissnes  derived,  from  all  the  </erm-laj/ers. 
j  The  heterotopous  tissue=growths.  which  are  classed  m  ilh  tlie  teratoi<l 
|umors  may  occur  in  the  most  various  organs,  but  are  more  frequently 
found  in  certain  regions  than  in  others.  Among  the  more  common 
jumors  of  this  class  are  the  chondromata  and  chondromyxohiata  of  the 
jalivary  glands  and  the  testicle,  osteomata  of  the  luuseles,  lipomata  of 
he  pia  mater,  adenosarcomata  of  the  kidney  containing  striped  muscle, 
iud  the  adrenal  tumors  found  in  the  kidne^'.  Among  those  occurring 
iiore  rarely  are  the  chondromata  and  osteomata  of  tlie  skin  or  of  the. 
tiamniary  gland,  rhabdomyomata  of  the  testicle,  etc. 

The  occuri'ence  of  tissue-formations  in  regions  in  which  such  tissues 
ire  not  normally  pieseut  can  be  explained  in  part  by  the  assumption  that 
'ells  or  groups  of  ceMs  of  a  tissue  have  not  undergone  a  normal  ditTei- 
jutiation  into  detinite  tissue-forms,  but  retain  the  capacity  of  forming 
lifferent  kinds  of  tissues.  Nevertheless,  in  many  cases  t  lie  e\i»lanat  ion 
i>  to  be  sought  rather  in  a  germinal  aberration  or  a  misplacement  of 
jissue,  in  that  either  in  early  eml)iyonic  life  end)iyonal  cells  of  oiu^ 
|rgan  find  their  way  into  the  aulage  of  another  organ,  oi-tliat,  later,  tis- 
uesiu  process  of  development  or  already  formed  are  dis])laced  fiom  their 
jormal  position.  The  first  process  can  be  inferred  only  from  the  sul)- 
pquent  appearance  of  jxithological  tissue-formations;  th«^  latter,  on  the 
Ither  hand,  may  at  times  be  recognized,  hiter  on,  in  the  anatomical  n-- 
titions.  Thus,  for  example,  in  the  letrograde  changes occuiiing  in  her- 
iiasof  the  sacral  portion  of  the  spinal  cord,  adipose  tissue  and  muscle-tis- 
lie  may  find  their  way  into  the  spinal  canal  and  the  arachnoidal  sac  and 
jrow  around  the  nerves.  Arnold  obserxed  tiansposition  of  fat-tissue, 
jlaud-tissue,  cartilage,  and  neuroglia  at  the  lower  end  of  the  tiiink,  in  a 

■    ise  of  myelocyst  with    complete  absence  of   the  lumbar,   sacral,   and 
pccygeal  portions  of  the  spinal  column,     lie  also  found  in  a  lipomatous 

;   h-atoma  of  the  fiontal  region  that  the  intracranial  i)ortiou  of  the  tumor 

Pmunicated  with  the  extracranial  through  a  defect  in  the  cranium. 
rh<' teratoid  cysts  may  l)e  divided  into  two  great  groups:  tlie  ect<t- 
ml  on  the  (me  hand,  and  the  cniodcrmal  and  mesodermal  rpithelial  ci/x(h 
'nthe  othei'. 
I  I    Th<'  ectodermal  cysts  vary  in  size  from  that  of  a  jtea  to  that  of  a 
jian's  list.     Their  walls  i)resent  ectodermal  characteiisti<-s,  either  in  that 
iiey  consist  only  of  a  smooth  connective-tissue  meiubrane,  covered  with 
jratified  squamous  cells — the  so-called  epidermoids;  or  the  cyst  walls 
I  »ay  present  all  tin- characteristics  of  skin— that  is,  contain  j.apilla-.  seba- 
^^   pons  glands,  hair  follich'S,  hairs  and  sweat-glands.  an<l  often  also  subcu- 
iineous  fat— the  so-called  dermoids  oi'  dermoid  cyst5  oi  dermatocysts. 
i 


486  TUMORS. 

The  cyst-conteuts  consist  eitlier  of  desquamated  liorny  cells  alone,  oi 
of  such  cells,  fat,  and  blond  hair.  i 

Upidennoiils  and  dermoids  are  found  chiefly  in  the  sAin  and  subcuta-> 
neons  tissues,  where  they  present  themselves  in  the  form  of  tumors  contain- 
ing  a pidtaceous  m(deri(d,  which  ve^emh\e  atherom(da,  i.e.,  tumors  causecl 
by  the  retention  of  secretion  in  the  excretory  ducts  of  the  sebacecui-; 
glands  and  in  the  hair-follicles.     They  are  also  found  at  the  sides  of  thd 
necJc  and    in  the  median  line  either  above  or  below  the  hyoid  bone 
further,  iu  the  thoracic  cavity,  particularly  in  the  mediastinum,  in  the  peri 
toneal  cavity  (rarely),  ^yelvic  cellular  tissue,  coccygeal  region,  and  in  the  raph, 
of  the  perineum.     Finally,  they  also  aijpear  icithin  the  cranium,  in  the  dun 
or  in  the  hypophysis.     Of  frequent  occurrence  are  the  intracranial  forma 
tions  which  are  known  as  cholesteatoma  or  as  pearl  tumors.     Thest, 
growths  vary  in  size  from  that  of  a  pea  to  that  of  an  apple;  they  fori); 
spherical  or  nodular  tumors,  having  a  white  satiny  surface,  and  consis 
for  the  chief  part  of  thin,  non-nucleated,  scale-like  cells,  arranged  ii; 
closely  crowded  laminae.     They  are  invariably  situated  at  some  point  o  i 
the  pia  (Bostrom),  and  at  such  places  the  vascular  pia  is  covered  wit| 
stratified  squamous  cells,  which  iu  the  course  of  years  produce  the  deli- 
cate epithelial  scales  of  which  the  tumor  is  composed.     The  neighborin 
brain  tissue  and  the  arachnoid,  which  may  in  part  extend  over  the  growttj 
are  not  concerned  in  the  formation  of  the  horny  scales.     In  rare  case! 
cholesteatomata  may  contain  sebaceous  material  andjine  hairs  in  additioj 
to  the  horny  scales  and  cholesterin.     In  these  cases  there  may  be  founj 
seated  here  and  there  upon  the  pia  dermal  structures,  i.e.,  true  skin  tissil 
containing  sebaceous  glands  and  hair-follicles,  from  which  the  sebaceoij 
material  and  hairs  found  in  the  growth  arise.     The  simple  cholesteat' 
mata  may  therefore   be  designated   as    epidermoids   (Bostrom),   tho:i 
containing  hair  as  dermoids.     Cholesteatomata  occur  at  the  base  of  tl! 
brain,  in  the  neighborhood  of  the  olfactory  lobe,  tuber  cinereum,  corpi| 
callosum,  choroid  plexus,  pons,  medulla  oblongata  (very  rarely  in  tlj 
spinal  cord),  and  in  the  cerebellum. 

The  dermoids  and  epidermoids  under  consideration  prol)ably  o> 
their  origin  to  a  transplantation  of  epithelial  germs  to  the  sites 
question.  In  the  case  of  the  epidermoids  probably  only  embryonal  e]j 
thelial  cells  are  transplanted ;  iu  dermoids  embryonal  dermal  tissue  •> 
also  transplanted.  Tiie  intracranial  cholesteatomata  originate  prolj- 
bly  in  an  early  implantation  of  epidermal  anlage  in  the  pia..  Mediasr 
nal  dermoids  probably  depend  upon  disturbances  of  development  of  1j) 
thymus,  which  arises  from  the  ectoderm.  The  dermoids  on  the  sidesl" 
the  neck  arise  from  remains  of  the  branchial  clefts,  particularly  of  'h 
second;  those  hanging  from  the  hyoid  bone  or  lying  beneath  it  are  prd- 
ably  to  be  regarded  as  the  remains  of  the  ductus  thyreoglossus.  Dermo  J3 
of  the  pelvic  cellular  tissue  may  be  exi)lained  as  arising  from  epithel,! 
inshoots  from  the  i^erineum. 

Simple  entodermal  and  mesodermal  epithelial  cysts  are  charact  • 
ized  by  a  lining  of  cylindrical  cells,  which  are  often  ciliated.  They  oc<jr 
most  frequently  in  the  broad  ligament  and  tubes.  They  are  found  sijo 
in  other  portions  of  the  peritoneal  cavity,  iu  the  intestine,  in  the  ueij^- 
l)orhood  of  the  trachea  and  bronchi,  in  the  lungs,  pleura,  neck,  tongK 
vagina,  glandular  organs,  etc.  They  form  cysts  varying  in  size  frn 
that  of  a  pin-head  to  that  of  a  man's  head.  \ 

The  occurrence  of  these  cysts  may  be  explained  in  most  cases  by  'e 


TERATOID    Tl'MOKS    ANT)    CVS'IS, 


487 


jersistence  of  foetal  glands  or  canals  or  by  llir  separation  throuRh 
lonstriction  of  portions  of  entodermal  or  mesodermal  epithelial  tubes. 

11  tlie  nock  ivniains  of  tlie  intcnial  l)iaii<'liial  clclts,  in  the  poshTJor 
)ortions  of  the  tongue  tlie  nMiiaiiis  of  the  diic'tiis  tliyi-eo,iLih)Ssiis  or  of 
rpithelial  buds  and  glands  develo})!!!-;' fioin  the  same,  in  Ih;'  (esophagus 
luul  resi)iiatorv  tract  snaivd-off  ixutious  of  tlie  intestinal  canal  or  of 
he  ail-passages,  or  remains  of  the  commiinication  between  alinieiitary 
ract  and  air-passages,  may  form  the  foundation  for  the  development 
)f  such  cysts.  In  the  broad  ligament,  uterus  wall,  and  tubes  tlie  cysts 
irise  from  remains  of  the  canals  of  the  Wolilian  duct  and  the  duct  of 
iiirtuer;  in  the  tubes,  cervix,  i)ortio  vaginalis,  vagina,  and  hymen  they 


/-■■,K 


I  Fk;.  ;jg.").— Adenoma-like  isolation  in  tlie  submucosa  of  a  portion  of  the  mucins  meinbiaiic  of  the  small 
hiestine,  ffiving  rise  to  a  ridge-lllie  prominence  of  the  mucosa  2  cm.  in  length  (alc^iliul,  hu'maluxvliii). 
irom  a  child  six  weeks  of  age.  «,  h,  c.  Normal  intestinal  wall;  d,  e,  portions  of  mucosa  included  within 
16  submucosa ;  /,  mucous  tissue  rich  In  cells.    X  35. 

'rise  from  the  remains  of  the  latter;  in  the  i)eritoneal  cavity  in  part  from 
!iiared-off  portions  of  the  intestine  (oitrroci/st.s),  or  in  i)art  irom  portions 
'•f  the  \irachus  '{umchus-cysts).  Within  the  glands— for  exauipU',  the 
'iver  or  the  kidneys — portions  of  the  gland-tubules  may  become  con- 
jtricted  off  during  the  period  of  deveJopmeiit,  and  later  develop  into 
ysts  (adenocysts). 

Cj'Sts  located  in  the  cential  nervous  system  or  its  imniediate  ueigh- 
Horhood — for  example,  at  the  lower  end  of  the  trunk— may  arise  from 
jlie  medullary  canal  ()ni/eloq/stfi),  in  the  latt«'r  place  also  from  remains  of 
he  hind-gut  (mterocysts). 

The  origin  of  the  cysts  lined  Mil h  cylindrical  epitlieliinu  can  usually 
)e  determined  only  from  their  ])osition  and  the  cliaracler  of  their  walls, 
)ut  in  the  majority  of  cases  tin;  origin  can  usually  l»e  ascertained  iK-yoiid 
iloubt.  The  diagnosis  can  be  made  with  the  greatest,  certainty  when  the 
inisplacement  of  the  separated  portion  is  slight  (Fig.  ;{<»5,  (/,  c),  and  when 
he  formation  still  shows  clearly  the  character  of  the  mother-tissue. 


4S8  TUMORS. 

The  sigiiiflcauce  of  ectodermal,  entodei-inal,  and  inesodenual  cyi 
dependent  upon  their  position,  size,  and  the  secondaiy  changes  whic| 
occur  in  them.     Their  size  varies  from  that  of  a  pin-head  to  that  of  | 
man's  head.     Among  the  secondary  changes — aside  from  inflammatk 
may  be  mentioned  the  development  of  adenomata  and  carcuiomata.     Fd 
example,  remains  of  the  Wolffian  body  which  are  present  in  the  dor 
wall  of  the  uterus  near  the  angles  of  the  tubes  (von  Recklinghausen),  cf 


Fig.  366.- Adenoma-like  remains  of  the  Wolffian  body,  witbin  the  uterine  musculature  (formalin,  aloi it; 
haematoxylin,  eosin).    a.  Muscle  tissue ;  b,  glandular  tissue ;  c,  sections  of  vessels.    X  100. 

in  the  broad  ligament  in  the  inguinal  region  (Aschoff,  Pick)  may  gi  | 
rise  to  adenomata,  cystadenomata  (Fig.  366,  h),  or  adenomyomata.  D<| 
molds  may  be  the  seat  of  development  of  a  squamous-ceUed  cancer  (branchij 
genie  and  subcutaneous  carcinoma);  while  from  separated  portions  of  tj 
intestinal  mucous  membrane  (Fig.  36.j)  it  is  probable  that  cyliudric;! 
celled  carcinomata  may  take  their  origin.  Ci/sfs,  ci/stadcnoinafa,  and  co^ 
cinomata  may  develop  in  the  jaw  from  misplaced  portions  of  tli«^  cpithrJi' 
anlage  of  the  teeth. 

Literature. 

(Ectodermal,  Entodcrmal ,   and  Mesodermal   Teratoid  <[i/-sfs,   and.  Solid  ' 
Teratomata. ) 

AlbrecM:  Nebenmilzen.     Beitr.  v.  Zie«ler,  xx.,  1S96. 

Arnold:  Hygroma  colli  congenitum.  Virch.  Arch.,  33  Bd.,  1865;  Angeb.  lipomatuf 
Teratom  der  Stirn.  lb.,  43  Bd.,  1868;  Congenitales  zusammengesetztes  Lipom  ( ' 
Zunge  und  des  Pharynx  mit  Perforation  in  die  Schadelhohle.  lb.,  .50  Bd.,  18: 
Behaarte  Polypen  der  Rachenmundhohle.  lb.,  Ill  Bd..  1888;  Ein  knorpelhalti,!; 
angeborenes  Fibrom  des  Scheitels  mit  Hypertrichosis.  Beitr.  v.  Ziegler,  viii.,  18'; 
Myelocyste,  Transposition  von  Gewebskeimen  u.  Sympodie.     lb.,  xvi.,  1894.    ' 

Aschoff:  Cysten,  Ergebn.  d.  allg.  Path.,  ii.,  1897  (Lit.);  Cystisches  Adenofibroiu :. 
Leistengegend.     Monatsschr.  f.  Gebh.,  ix.,  1899.  : 


TKHATOll)    'I'l MOKS    AM)    CVSTS.  4,S<) 

iskanazy:   Die  bosartigen   Geschwiilste  dcr  in  ilor  Nioro  oingeschlossoncii  Nohoii- 

nierciikoime.     Beitr.  v.  Ziejjlcr,  xiv.,  1893. 
eneke:    Zur  Lehre  v.  d.  Versprenjivmg  von  Nehennioronkeinion  in  don  Xiorcn.  ncl.st. 

Bonicikungen  zur  alljr.  Onkolofjie.     Beitr.  v.  Ziejiler,  x.,  lSi)l. 
Dstrdm:    Piale  Epidennoide.  Dcrnioide  u.  hiponie  u.  duraie  Dernioidc     Cl.l.  f.  all". 
I     Path.,  1S97  (Lit.). 

jruns,  P.:  Brancliiogene  Carcinonie.     .Mittlioil.  a.  d.  cliir.   Kliiiik    /u    'I'liMnu'en.  i  , 
j     1S84. 

uttersack:   Congen.  Knorpelreste  am  llalso.     \'ircli.  Arcli..  IOC)  Bd.,  ISSd. 
liari:   Cienese  d.  Atheromcysten.     Cbl.  f.  allir.  Patli..  ISOO;    Zeitsdir.  f.  Ileilk.,  xii., 

ISOl. 
illen:    .\denomvonia  of  the  Hound  Ligament.     Johns  Hopkins  Hosp.  Bull..  is<)2. 
lyzewicz:   Retrosakrales  Dermoid.     B.  v.  Bruns,  :■!()  Bd..  lOOJ  (Lit. ). 
shier:  Atlieromc3-.sten  am  Halso.     Beitr.  v.  Bruns,  xx.,  ISOS. 
aichert:   Knorpel  u.  Knochen  in  d.  Tonsillen  (Reste  d.  2    Kcimcnbogensi.     ^■irc•h. 

Arch.,  141  Bd.,  1S9.5. 
:i)derlein :   Embrvon.  Driisengeschwul.st  d.  Nierengegend.     ('l)l.  f.  Krankh.  d.  ll.-irn- 

(.rg.,   1894. 
jssekker:  L^rachuscysten.     Beitr.  v.  Brun.s,  x.,  1893. 

Derth:   Flimmerepithelcysten  d.  Leber  u.  d.  Geliirns.     Virch.  Arch.,  '.'.')  Bd.,  lS(i('>. 
•ank:  Cholesteatom  cL  weichen  Hirnhiiute.     Inaug.-Di.s.s..  Marburg,  1S97. 
•anke:  Das  Atherom.     Arch.  f.  khn.  Chir.,  34  Bd.,  1887;    Vircli.  Arch.,    ILM  B.I., 

1890. 
;-obenius:   L'eber   einige  angeb.  Cystengeschwulste  des  HaLses.     Beitr.    v.  Ziegier, 

vi.,  1889. 
oebel:  Vom  Zahnsystem  au.sgehende  Kiefertumoren.     Cbl.  f.  allg.  Path.,  1897  (Lit.). 
i-awitz:  l'eber  die  sog.  Lipome  der  Nieren.     Virch.  Arch.,  93  Bd.,  1883. 
urlt:   Die  Cystengeschwidste  des  liaises,  BerHn,  1855. 

^sktoen:  Vitelline-Duct  Remains  at  the  Navel.     Amer.  Journ.  of  ()b.st.,  1893. 
ielbing:   Rhabdomyom  an  Stelle  d.  1.  Lunge.     Cbl.  f.  allg.  Path.,  ix.,  1898. 
■^ss:  Teber  eine  subcutane  Flimmercyste.     Beitr.  v.  Ziegier,  viii.,  1890. 
3usinger:   Hals-Kiemenfisteln  mit  Knorpelresten.     Virch.  Arch.,  29  Bd.,  1SG4. 
aldebrand:  T'nters.   liber  Spina  bifida   (Gewebstranspcsitionen).     Dent.    Zeitschr. 

f.  Chir.,  36  Bd.,  1893;  Langenbeck's  Arch..  46  Bd.,  1893;  Cysten  u.  Eisteln  d. 
i  Halses.  lb.,  49  Bd.,  1894;  Spina  bifida  (Gliom  in  Hydrencephalocele).  Deut. 
;    Zeitschr.  f.  Chir.,  36  Bd.,  1893. 

dieter:  Angeb.  Darmgeschwulst.     Beitr.  v.  Ziegier,  xix.,  1895. 

lachimsthal:  Spina  bifida  occulta  mit  Hyi)ertrichosis.     Virch.  Arch..  131  Bd.,  1893. 
villy:   Hvpcrnephromas  of  the  Kidney.     Phil.  Med.  Journ.,  1898. 
lihne:   Zur  pathol.  Histologic  d.  Cyst'enliilduns.     Virch.  Arch.,  158  Bd.,  1900. 
j.nnelong'ue  ct  Achard:   Traite  des  kystes  conijenitaux,  Paris,  1886. 
ulassez:   Sur  le  role  des  debris  epitheliau.x  paradentaires.     Arch,  de  phys.,  1885. 
lillory.   Sacrococcygeal  Dimples,  Sinuses,  and  Cysts.     Am.  Journ.  of  the  .Med.  Sc, 

1S92. 
hrchand:   Rhabdomyom  der  Dammgegend.     Virch.  .A.rch.,  100  Bd.,  1885. 
lirmet:   Les  kystes  congen.  du  raphe  genito-perineal.     Rev.  de  chir..  1895. 
],5yer:  Ueber  epitheliale  Gebilde  im  Myometrium,  Berlin,  1899;  Sub.serdse  Epitliel- 
j    knotchen  an  Tuben,  Lis.  latum,  Hoden  u.  Nebenhoden.     \'.  .V.,  171  Bd.,  190;!; 
:    Ektodermcysten  am  Lie.  latum,  am  Samenstrang  u.  Nebenhoden.     lb.,  168  Bd.. 
!    1902:   .\denom-  u.  Carcinombildung  an  der  Ampulle  d.  Giirtner.schen Ganges.    lb., 
'    174  Bd.,  1903. 

1  ntz:  Xabeladenom.     Deut.  Zeitschr.  f.  Chir.,  51  Bd.,  1899. 
liumann:   .Myoma  striocellulare  d.  Hodens.     Virch.  .\rch.,  103  Bd..  ISSO. 
Mtauf:  Schifddrusentumoren  im  Kehlkopf,  u.  d.  Luftrohre.     Beitr.  v.  Ziegier.  xi., 

1S91. 
Irez:   Branchiogene  Carcinome.     Beitr.  v.  Bruns.  23  Bd..  1S9'.). 

Jrmann:  Cv.sto.ses  Sacrococcygealteratom  (grosse  .Myelocystej.     .\rcli.  f.  kliii.  Chir., 
'    4!)  B.I..  1895. 

Jam:   iJerinoidcysten  des  Mediastinums.     Zeitschr.  f.  Heilk..  xvii..  l.S9(i. 
lole:  .\ngeb.  Cysten  d.  (Jenitoperinealraphe.    Beitr.  v.  Bruns,  xx..  1898. 
J-k:   .Vdenomyome  d.  Leistengegend  u.  d.  Scheidengewolbes.     Arch.  f.  Gyn.,  57  Bd., 
:    IS99. 
^ Recklinghausen:   I'ntersuchungen   iiber  Spina  l)ifida.     Virch.    .\rch.,    105   Bd., 

ISMl;    Die  Adenomyome  u.  Cvstadenome  d.  Cterus,  Berlin,  189(5. 
linhold:   Oelcy.ste  auf  d.  Schliifenschuppe.     Beitr.  v.  Bruns,  viii..  1892. 
Ichard:  Geschwulste  der  Kiemenspalten.     Beitr.  z.  klin.  Chir.,  v.  Bruns,  iii.,   18S8. 
Jge:  Retropentoneale  Dermoidcyste.     B.  v.  Ziegier,  xxxiv.,  1903. 


490 


TUMORS. 


Samter:   Ein  Beitrage  z.  I,ehre  v.  d.  Kiemengangsgeschwiilsten.     Virch.  Arch.,  If 

Bd.,  isss.  : 

Sanger:   Dermoidcysten  d.  Beckenbindegewebes.     Arch.  f.  Gyn.,  37  Bd.,  1895.       ; 
Schirkele:   Die  Lehre  von  den  mesonephrischen  Geschwiilsten.   Cbl.  f.  allg.  Path.,  x 

1904  (Lit.).  i 

Schmidt:    I'eber  die  Flimmercysten  d.  Zungenwurzel,  Jena,  1896. 
Schoch:  Cungen.  zahnhaitige  Cyste  der  Unterlippe.     Inaug.-Diss.,  Basel,  1893.         I 
Schulz:  Embryon.  Arschniirungen  v.  Epidermis.     Virch.  Arch.,  95  Bd.,  1884.  i 

Volkmann:  Branchiogene  Carcinome.     Cbl.  f.  Chir.,  xxii.,   1885.  ! 

Westenryk:    Mediastinalcysten.     Prag.  med.  Woch.,  xxv.,  1900.  ' 

Wette:  Fistehi  u.  Cysten  d.  Sacrococcygealgegend.  Langenb.  Arch.,  47  Bd.,  1894 
Wyss:  Zur  Kenntniss  heterologer  Flimmercysten.  Virch.  Arch.,  51  Bd.,  1870.  i 
Zahn:  Kiemengangscysten.     Deut.  Zeitschr.  f.  Chir.,  xxii.,  1885;    Myxosarkom  tf 

Wange  bei  se'chsmonatl.  Fotus.     Deut.   Zeitschr.  f.  Chir.,  xxii.,   1885;    Congi. 

Knorpeh-e.ste  am  Halse.     Virch.  Arch.,  115  Bd.;    Flimmerepithelcysten  des  Oe!- 

phagus  d.  Leber  u.  d.  Pleura.     Virch.  Arch.,  143  Bd.,  1896  (Lit.). 
Zoppritz:  Multiloculiire  Kiemengangscysten.     Beitr.  v.  Bruns,  xii.,  1894.        . 

►See  also  §  128.  | 

§  127.  Complex  teratomata  occur  most  freciuently  in  the  sexijl 
glands,  partly  in  the  form  of  dermoid  ci/sts  and  partly  as  solid  tumors  as\- 
eiated  ivith  muJtipJe  ci/sf -formation.  The  first  occur  particularly  in  lie 
ovary,  the  latter  in  the  testicles.  j 

The  so-called  dermoid  cysts  of  the  ovary  form  rather  thick- walii 
cysts,  varying  in  size  from  that  of  a  pea  to  that  of  a  man's  head,  and  ;je 
tilled  with  a  fatty  material  containing  blond  hair.  At  some  point  iu 
the  wall  there  will  be  found  extending  into  the  cyst-cavity  a  viUus-h'^, 
'nodular,  flattened,  or  septum-Jil-e prominenee,  irhich  is  covered  with  hairs  ild 


Fig.  3G~.— rortion  of  the  wall  of  a  dermoid  cyst  of  the  ovary,  a.  Smooth  wall ;  b,  prominence  < 
ing  of  fat  and  cutaneous  tissues ,  c,  swollen  protuberance,  bent  down  upon  Itself  above  and  beanDf 
and  teeth  (t().    Natural  size.  ' 

often  studded  with  teeth  (Fig.  367,   &,   e,  d).      The  upper  layers  ofj^is 
prominence  contain  the  characteristic  structures  of  the  skin  (Fig.Klo. 


TERATOID    Tl.MOKS    AM)    CYSTS.  491 

a,  ai,  a-i,  h),  namely,  Iiair-r..lli,-I,vs  will,  luirs,  s.'l)ac.M.us -lands  and  sweat- 
glands;  snheutaneons  tat  is  also  nsually  I)i«'s,mii  {f'j.  I,,  the  «i.M'prr 
layei-s  are  found  other  tissue-formations,  sueh  as  evsts  and  tubes  lined 
with  ciliated  eolumuar  epithelium   (d),    bone   (c/),  "cartilaj.'e,    teeth  (//) 


Flo<  U«i8.— Section  through  a  prominence  in  a  multilocular  dermoid  (alcohol,  nitric  acid,  hirmatoxylin. 
^iiein).  rt,  tii.aj.  Epidermis:  /j,  corium  with  sebaceous  plands;  c.  sinus  lined  with  squamous  cpllhclluni : 
'I.  sinus  lineil  with  cylindricai  epithelium;  e,  tubular  glands;  /,  fat-tissue;  (/,  iKiiie ;  It,  t«flh;  i,  Imiin- 
tjssue  with  corpora  amylacea ;  k,  ovarian  tissue.    X  5. 

niuscle-ti.ssue  (also  heart-musele  [Katsnrada] ).  luaiii-tissuc  (/).  ncivrs. 
I^roupsof  j;an.i;lion-eells,  mucous  iihinds,  intestinal  mucosa.  :in<l  thyroid 
|ti.s.sue,  ;ls  well  as  ])i<,nnente(l  formations  rcscmhlin-;  the  iiidiment;iry  lis- 
[sue.s  of  the  eye.  Kidney  and  liver  tissiu'S  have  not  yet  been  fouml.  Tlie 
liemaining  portion  of  the  ey.st-wall  of  the  dermoid  is  either  covered  with 
leylindrical  epithelium  or  is  l)are;  if  hairs  are  ])re.sent  in  tliis  portion, 
itliey  are  the  residt  of  ji  secondary  implantation,  and  m;iy  b«'  surroumled 
by  granulation-tissue,  often  also  by  jiiant  cells.  If  in  associ;il  ion  witli 
ithe  cysts  containing-  fat  and  hairs  llieii^  are  also  found  cysts  tilled  with  a 
jserous  or  mucoid  tluid,  th«^  latter  may  b(^  e.\plaiiie<l  as  iirisin;;  t hiou^di 
'the  cystic  dilatation  of  spaces  of  the  dermoid  which  are  Jinctl  witii  cylin- 
jdrical  cells.  M(ne  fre(iuently,  liowever,  they  represent  t'ormations  re- 
iSulting  from  the  cystic  dej,^enerat ion  of  nei}::hboriu;,'  ovari:in  follicles  (»r 
|0f  adenomatous  new-growths.     The  ovary  nmy  be  entirely  destroyed  by 


492  TUMORS. 

the  dermoid ;  but  remains  of  its  tissue  are  often  present  (A-).  Inver' 
rare  cases  several  dermoids  may  develop  coincidently  in  one  ovary;  ii 
double-sided  occurrence  is  seen  in  about  fifteen  ]ier  cent,  of  all  cases 
Ovarian  dermoids  are  observed  most  frequently  iu  individuals  of  middl 
age,  but  occur  also  iu  children.  . 

The  most  characteristic  feature  of  ovarian  dermoids  lies  in  the  fiuj 
that  they  contain  elements  of  all  three  germ-layers,  and  that  a  certain  la'l 
in  the  arrangement  of  the  different  elements  is  observed.  The  derivij 
fives  of  the  ectoderm  and  mesoderm,  in  particular  the  skiu  and  its  a]'! 
pendages,  also  bone  and  teeth,  and  often  brain  substance,  are  developel 
to  the  most  marked  extent;  while  eutodermal  formations,  cyliutlrica- 
celled  tubules,  and  mucous  glands  are  ordinarily  developed  to  a  miu' 
less  degree,  and  lie  concealed  in  the  deeper  parts  of  the  growth.  Tlj 
structure  of  the  growth  as  a  whole  gives  the  impression  of  a  rudimentaA 
emhryo  with  an  unequal  development  of  ecto-  and  entodermal  tissue,  ar 
such  tumors  have  therefore  been  appi-opriately  designated  as  embry'; 
mala  (Wilms).  j 

The  solid  teratomata  of  the  ovary  are  much  more  rare  than  the  dei 
moid  cysts.  They  form  tumors  which  are  composed  of  a  confused  mi  \ 
ture  of  the  most  varied  tissue-formations,  viz.,  epidermis,  epitheli 
pearls,  hairs,  sebaceous  glands,  sweat-glands,  tubules,  and  cysts  limj 
with  ciliated  epithelium,  acinous  glands,  connective  tissue  rich  in  cell' 
adipose  tissue,  muscle,  cartilage,  and  bone.  In  rare  cases  teeth,  inte! 
tine,  thyroid  and  brain  tissue  of  a  rudimentary  character  may  be  preseDJ 

Since  these  formations  also  contain  elements  of  all  three  germ-layei], 
and  are  distinguishable  from  the  dermoids  only  through  the  lack  of  aij 
regular  order  of  arrangement  of  the  different  tissues,  and  through  t'j 
more  rudimentary  development  of  the  individual  tissues,  they  may  liki 
wise  be  classed  with  the  embryomata.  AVith  reference  to  their  lack  I 
any  structural  organization  approaching  that  of  the  human  embr}| 
Wilms  has  designated  these  formations  as  embryoid  tumors. 

Since  the  embryoma  contains  elements  of  all  three  germ-layers,  ' 
part  in  orderly  arrangement,  the  genesis  of  such  a  tumor  inay  be  e| 
plained  by  the  assumption  of  a  development  from,  an  ovum.    Bonnet  regais 
it  as  probable  that  either  in  the  development  of  a  fertilized  ovum,  \ 
the  early  stages  of  division,  a  blastomere  (or  se-seral)  may  be  delayed  'li 
division  and  later  give  rise  to  an  independent  formation  containing  ej- 
ments  of  all  germ-layers,  or  that  (Marchand)  a  fertilized  polar  body  (t.' 
fertilization  of  the  polar  body  has  been  demonstrated  in  vertebrates)  fir;< 
its  way  between  the  blastomeres  of  a  developing  ovum,  and  later  devek  ■; 
within  the  embryo.     The  first  assumption  seems  more  probable,  and  t/ 
embryomata  of  the  ovary  may  consequently  be  regarded  as  rudimenti 
unioval  twin  malformations  {%  128),  which  are  to  be  placed  in  the  sa 
category  with  the  foetal  inclusions  of  other  organs.     The  fact  that  tb 
ovaries  (and  testicles)  form  the  favorite  seats  of  such  growths  is  probal 
dependent  upon  the  fact  that  the  urogenital  anlage  in  its  earliest  sti' 
forms  relatively  such  a  large  j^art  of  the  embryonal  anlage  (Bonnet), iji' 
that  the  blastomeres,  from  which  the  sexual  glands  later  arise,  m<J2 
easily  than  others   take  on  an  especial  development,  that  may  leado 
the  formation  of  a  rudimentary  twin. 

The  teratomata  of  the  testicle  occur  most  frequently  in  forms  wh,li 
according  to  their  structure  are  designated  as  adenocystoma,  chom\- 
adenoma,  chondrosarcoma,  adenomyosarcoma,  cystosarcoma,  cystocarcino) ', 
etc.     In  some  cases  the  formation  of   cvsts  with  finid  contents  fois 


TERATOID    TUMORS    AM)    CYSTS, 
tl.o 


493 


jhe  most  strikiiiii"  foaliiro  ol'  tlio  tuiiMir  (Fiji;.  3lM>);  in  otluT  cast' 
jysts  are  found  only  in  certain  parts  of  the  jj;ro\vth;  and,  linallv,  in 
i;"till  other  eases  the  tumor  may  be  solid  thronjihont.  Tiicse  jiicmlhs 
iiiay  reach  the  size  of  a  child's  head.  They  may  he  con;;enilal,  l»ut  de- 
!  elop  more  fiequently  in  adult  life,  and  Iheii  -iiow  lapidly. 

The  lininji- of  the  cysts  is,  as  a  rule,  of  entiuhMinal  chara<'ler,  l)iil  may 
ary  in  one  and  the  same  cyst  (Fig.  300).  Simjjle  cubical  (Fig.  ;i»i;i,  h) 
\\\d  cylindrical  e]dthelium  either  with  or  wilhout  cilia,  as  well  as  slrali- 
iied  ciliated  epithelium  ((h  and  pigmented  epithelium  (r),  maybe  found. 
I  Ectodermal  (issue  is  ])resent  only  in  scanty  amount,  and  i.s  limited  to 
itiirmented  epithelium  or  to  scattered  groui)s  of  cells  showing  coi-nilica 
lion;  or  it  may  be  entirely  absent,  or,  at  all  events,  cannot    be  demon 


M^^Si 


5^5"  '•  K" 


mm^:y^. 


'^^ii'^^^ 


•>;/»•'-;.• 


Fin.SfiO.  ronpcnital  arlpnopvsfoma  (teratoma)  nf  tlio  tosticle  with  pisriiKMilatioii  atnl  fonimtiDn  I'f  ciir- 
lacH  (MfilltT's  Iluifi.  li;i'niat()xvlin).  ((.  (■(iiiiit-ctivc-tissiic  stmina  ;  /;,  simple  cuiiical  .•pilticlliini ;  v.  stniti- 
ylinilrical  epiilii'liiiii] ;  '/.' slratitU'ii  cilJai.Ml  cvliiKlrical  i-pittn-liiun  :  « ,  pit'iiii-riKMl  rpiiln'iiiitn  llnlnir 
!arnl-tut)iilp;  f.  pitriiicntcd  conncctive-tissiip  cells  ;  (/,  caitilatri'  in  ((niniMtivr  ilssiir  ;  /i.  c'ltilap'  Ivliitf  In  ii 
larul-tuhiile.    (Section  talien  fniiii  tumor  pictured  in  Fig.  Ijati.  i  UKi. 

trated  in  the  case  of  tumors  of  large  si/e.     besides  the  evsts,  miicnns 
lands  may  also  be  found. 
Of  the  connective-tissue  substances,  fibrous  tissiM-,  myxomatous  tis 

ue,  cartilage  (Fig.  8G9,  r/,  1\),  and  occasionailx  ais s<le(|-'ig.  ;;:(»,  it), 

lat  tissue,  and  more  j-arely  bone,  are  piesent. 

I  According  to  investigations  by  Schlagenhanfer,  AN'lassow,  Iwisel.  and 
rthers,  the  teratomata  of  the  testicle  may  also  contain  tissue-formations 
jorresponding  in  their  structure  to  the  malignant  chorit)ei»itheliomata, 
haracterized  in  i)ait icular  by  syncytial  fornuitions. 


494  TUMORS. 


Teratomata  of  the  character  of  dermoids,  containino;,  as  in  the  ca 
of  the  ovarian  dermoids,  snch  structnres  as  skin,  brain  tissue,  crau: 
and  tracheal  tissues,  and  more  rarely  teeth  and  structures  resembli 
the  eyes,  are  of  rare  occurrence  in  the  testicles,  but  are  found  both 
children  and  in  adults. 

To  what  extent  tlie  different  teratomata  of  the  testicles  are  to 
classed  with  the  embryomata,  or  to  what  extent  they  can  be  explain l 


I 


■ 

Fig.  370.— Teratoma  (adenomyosarcoma)  of  the  testicle  (formalin,  haematoxylin,  eosin).    a,  Cellular  tija 

■with  hnnrjQ  nf  miicplA  •   h    criQnrJ.tiihiild        V  lOH  1 


With  bands  of  muscle ;  b,  gland-tubule.    X  1(XJ. 

by  the  assumption  of  tissue-implanations  at  later  stages  of  embryoil 
development,  cannot  at  present  be  determined.  When  elements  of  ;1 
the  germ-layers  are  present  in  the  tumor,  the  assumption  is  justified  tljt 
the  growth  belongs  to  the  embryomata  or  embrj'oid  tumors,  and  m 
arisen  in  the  same  manner  as  has  been  assumed  in  the  case  of  the  ovarii 
dermoids.  The  occurrence  of  syncytial  foi-mations  speaks  in  favor  f 
this  assumption.  The  presence  of  single  tissue-formations — as,  for  ';• 
ample,  of  cartilage  or  of  muscle — in  tumor-formations  of  a  more  sim  b 
character,  maj^  be  explained  by  the  assumption  that  such  tissues  fji 
their  way  into  the  aulage  of  the  testicle  during  the  period  of  embryo  \ 
development. 

The  proliferations  of  chorio-cpitheJial  character  found  within  teratomata  of  ie 
testicles  are  beUeved  by  Schlagenhaufer  to  depend  upon  the  development  of  fciil 
mernbranes,  and  he  regards  the  myxomatous  tissue  present  in  such  tumors  as  re;;*-'- 
senting  the  chorionic  stroma.  According  to  Marchand  and  RiscI,  they  are  to  be  regarjd 
only  as  products  of  the  foetal  ectoderm  having  the  same  histogenetic  significance  as  je 
other  ectodermal  structures  of  the  teratoma.  It  is  yet  to  be  determined  to  wnt 
extent  corresponding  ectodermal  formations  occur  in  teratomata  of  other  org.'|3. 
Pick  found  them  in  a  teratoma  of  the  ovary  in  a  nine-year-old  girl.  Further,  it  is  t'«e 
noted  that  syncytial  formations  occur  in  tumors  (angiosarcoma,  endothelioma)  ha-'ijg 
nothing  to  do  with  foetal  ectoderm.  It  cannot,  therefore,  he  reganled  as  positi'jy 
determined  that  the  syncytial  formations  in  teratomata  of  the  testis  actually  cciJ- 
spondto  a  chorio-epithelioma.  Wlassow  believes  that  the  chorio-epitheliomatous.  > 
liferations  observed  by  him  in  tumors  of  the  testis,  and  designated  by  him  asepitheWta 


TERATOID    TrAIOHS    AND    CYSTS.  40") 

pcytiomatodrs.  are  to  be  rejjanled  as  (k'livativcs  of  iiu-oiiii)l('lely  (levcloiicd  cpillicliiiiu 
icmbrj-onal  gland  tubules. 

Literature. 

{Teralomata  of  the  Sexual  (ihi)nh.) 

aspach:   Teratoma  strum,  thyreoideale  ovarii.     Pathol.  Soc.  of  Phil.,  vi.,  lUO'A. 
•nsperger:    Dermoidcyste  des  Ovariums.     Virch.  Arch..  loG  Bd.,  ISDi). 
mdler:    Die  Dermoidcysten  des  Ovariums,  Berlin,  1900;    Amer.  Journ.  of  Obstet., 

1901. 
Iiumgarten:   Dermoidcj'sten   d.   Ovariums  m.   auKenahnlichon   Bilduiifron.     \'ircli. 

Arch..  107  Bd..  1887. 
|pnnet:  Gicbt  es  bei  Wirbelthieren  Parthenogenesis?     Ergebn.  d.    .\iiat.,  i\..  Wics- 

Ixulen.  1900:   Aetiologie  d.  Embryonic.     Monatsschr.  f.  Gebh..  1900. 
I^lbet:   Patliogenie  des  tumeurs  heterotopiques.     L'Un.  mod.,  1895. 
iHansemann:   Chorionepitheliom.     Z.  f.  Gebh.,  51  Bd.,  1904. 
ktsurada:   Zur  Lehre  v.  d.  sog.   Dermoidcysten  d.  Eierstocks.     Beitr.   v.  Zioglcr, 

XXX..  1901. 
hckel:    Hodenteratom.     Chir.  Beitr.  Festschr.  f.  B.  Schmidt,  Leipzig,  189C>. 
hlaczek:  Dermoid  d.  Ovariums  m.  Bauchfellmetastasen.     Virch.  Arch.,  7.")    ]\t\., 

1S79. 
[irchand:  Teiatom  des  Ovariums.     Bresl.  arztl.  Zeit.,  1881. 
Iirx:  Tumor  (Hiimangiosarkom)  der  Leber.     Beitr.  v.  Ziegler,  x.xxvi.,  1904. 
Ifcumann:   Dermoid  d.  Ovariums  m.  centraler  Nervensubstanz.     Virch.  .Vrdi..   |(il 
,    Bd..   1SS6. 

Ick;  Epithelioma  chorioectodermale.     Berl.  klin.  Woch.,  1904. 
liUiet  I'l  Costes:   Les  epitheliomes  du  testicule.     Rev.  de  chir.,  1895. 
Ibbert:  Neuroepitheliale  Bestandt.   in   Embryomen.     Verb.  d.  D.  oath.  Cles.,   vi., 

1904. 
Isel:   Teber  das  maligna  Chorionepitheliom,  Leipzig,  1903  (Lit.). 
Ejbbe:  Tumeurs  dermoides  de  I'ovaire.     Ann.  de  la  Soc.  de  med.  d.  Gand,  1S98. 
ixer:  Teratom  (geschwulstart.  Wuch.  embrvon.  nervos.  Sub.st.).     Beitr.  v.  Ziegler, 
,    XXXI.,   1901. 

Sheiber:   Solides  Ovarialteratom.     Virch.  Arch.,  133  Bd..  1893. 
Shlagenhaufer:    Chorionepitheliom   u.     traubenmolenart.    Wucherunerpn    in   Tera- 

tornen.     Wien.  klin.  Woch.,  1902,  u.  Verb.  d.  D.  path.  Ges.,  v.,  Berlin,  1903. 
Eiinert:   Embr\'oide  Geschw.  d.  Keimdriisen.     V.  .\..  174  Bd.,  1903. 
lufifer:  Carcinomatose  Degen.  v.  Ovarialcysten.     Virch.  Arcli.,  142  Bd..  1896. 
Vims:  Dermoidcysten  ii.  Teratome.     Deut.  .\rch.  f.  klin.  Med.,  55  Bd..  1895  (Lit.); 
'.    Die  .soliden  Teratome  d.  Ovariums.     Beitr.  v.  Ziegler,  xix.;    Die  teratoidon  (Ic- 

schwiilste  d.  Hodens.     lb.,  xix..  1896  (Lit.");  Embryome  u.  embr\-oide  Tumoren  d. 
'    Hodens.     Deut.  Zeit.  f.  Chir.,  49  Bd.,  1898;    Multiple  Embryome  d.  Ovariums. 

Monatsschr.  f.  Gebh.,  1899. 
Massow:    Pathogene.se  d.  sog.  Sarcoma  angioplastique.     V.  A..  169  Bd..  1902. 
Vmagiva:  Dermoidcyste  d.  Ovariums  m.  krebsiger  Degeneration.     Virch.  .Vrch.,  147 

Bd..  1897. 
!    See  also  §§  126  and  128. 

I   §128,  Teratoid  cysts  of  a  complicated  structure  and   solid  tera 

tmata  are  I'ouiid,  outside  of  the  sexual  tilaiuls,  in  llie  same  rejiioiis  as 
t  '  simple  teratoid  cysts,  but  show  a  i)artieu]ar  jjiedileetion  for  llu-  re;,noii 
<illie  coccyx.  The  complex  character  of  tlie  ei/.sts  is  shown  i)y  (in*  pres- 
fjce  iu  the'cyst-wall  of  cartilage,  bone,  fat  tis.siie,  luucous  glands,  smoolli 
:|<1  striped  muscle  fibres,  nerve-tissue,  and  tis.sue  of  a  sarcomatims  or 
(Ircinomatous  nature.  Dermoid  cysts  may  also  contain  teetli,  and  furfhei- 
^«o  ciliated  epitlielial  cyst.s.  The  .solid  trndomalu  occui'.  in  I  he  first 
Ijice,  ii^  lid  in/  poll/pi  (nose,  throat,  and  mouth) — that  is.  as  p(»l\p(>id  lu 
i!)rs  covered  wiili  hairy  skin,  and  consisting  e.ssenfialiy  of  adipose 
tlsue,  Mhich  may  also  contain  mu.sde  tibres,  cartilage,  Ixmes,  teetli.  and 
f'^t.s.  Another  group  consists  of  those  lidneiitumors  whi<-li.  in  addition 
Mnbnlar  glands,  inclose  sarcomatous  tissue,  cartilage,  fibrous  ti.ssiie. 
Hi  pose  tissue,  and  muscle  tissue,  in  rare  cases  also  ectodernuil  tissues. 


496  TUMORS. 


Ill  the  vagina  and  cervix  uteri  of  cliildreu  there  occur  tumors,  for  t 
greater  part  of  a  racemose  character,  which,  in  addition  to  conuecti 
tissue,  myxomatous  tissue,  round  and  spindle-celled  tissue,  also  contfi 
smooth  and  stiiped  muscle-fibres,  and  in  rare  cases  also  cartihioe.  ] 
ually,  there  occur  tumor-like  growths  of  a  very  complicated  structure  i 
the  cranium,  thorax,  abdomen,  urinary  bladder,  neck,  lower  jaw,  and  esj. 
cially  in  the  region  of  the  coccyx.  They  contain  the  most  varied  formsif 
tissue:  counective  tissue,  adipose  tissue,  cartilage,  bone,  gland  tissi;, 
muscle,  uerve  and  brain  substance,  as  well  as  ectodermal  and  entoderal 
cysts.  They  may  further  inclose  rudimentary,  or  completely  formed,  r 
at  least  easily  recognizable,  portions  of  the  body.  ' 

Both  the  complex  teratoid  cysts  and  the  solid  teratomata  are  \ 
many  cases  to  be  regarded  as  local  disturbances  of  development  ch- 
acterized  by  a  misplacement  of  tissue  or  a  separation  of  tissues  y 
constriction  within  a  single  individual  {monogerminal  tissue-impln)  • 
tion,  autochtJwnous  teratoma  ).  The  hairy  polypi  of  the  throat,  the  cysticlr 
solid  teratomata  at  the  base  of  the  skull  or  in  the  hypophysis  maybe  ■;- 
plained  by  the  assumiition  of  a  misplacement  of  ectodermal  tissue.  Ije 
presence  of  cartilage  and  mucous  glands  in  teratoid  cysts  of  the  niedi'- 
tinum  may  be  explained  by  the  proximity  of  the  trachea.  The  teiat  .1 
mixed  tumors  of  the  kidney  may  be  explained  by  the  assumption  thatii 
the  kidney  region,  in  addition  to  kidney-tubules  and  remains  of  le 
Wolffian  body,  products  of  the  mesenchynia  aiising  from  the  myotce 
may  undergo  i^roliferation.  The  occurrence  of  squamous-celled  fori!;- 
tions  in  such  tumors  must  depend  upon  the  fact  that  ectodermal  tisie 
has  found  its  way  into  the  kidney  anlagc.  The  presence  of  stri;|d 
muscle-fibres  of  cartilage  in  tumors  of  the  vagina  and  uterus  isexplaiii- 
ble  by  the  assumption  of  an  implantation  of  myotome  or  of  anlage  of  |e 
vertebrae  (sclerotome) ;  but  many  writers  hold  the  opinion  that  stri  jd 
muscle  may  be  formed  from  unstrii^ed.  AVilnis  believes  that  the  Wolfiu 
duct  and  its  development  give  occasion  to  and  are  the  cause  of  the  i- 
plantations  into  the  cer\ix  and  vagina.  In  the  case  of  the  teratomatpf 
the  coccygeal  region  the  manifold  character  of  these  growths  may  be  c- 
plained  by  the  fact  that  portions  of  the  terminal  vertebrte,  of  the  pells, 
and  of  muscular  tissue,  as  well  as  remains  of  the  neuroenteric  ca;l, 
the  hind-giir,  and  the  medullary  canal,  take  i»art  in  the  formation  of  .'le 
tumor.  In  the  intracranial  teratomata,  as  well  as  in  the  simple  dernio  s, 
tissue-implantations  probably  form  the  basis  for  the  growth.  Moreo  ;r, 
there  exists  indeed  the  possibility  of  another  mode  of  origin  for  iV-^ 
growths — namely,  the  presence  of  a  rudimentary  twin,  a  bigermi)mHi' 
plantation.  Such  an  assumption  is  well  founded  in  all  those  casein 
which  the  teratoma  contains  fully  developed  or  rudimentary  parts  of  le 
body,  or  tissue-formations  which  cannot  be  explained  by  the  assump  )» 
of  a  misplacement  of  the  tissue  elements  of  a  single  foetus  at  the  sp<  J» 
question.  I'^kehorn  regards  the  complex  dermoids  of  the  inediasti'u, 
which  contain  skin,  cartilage,  bone,  and  the  constituents  of  mucous n.U' 
braiies,  as  bigerminal  implantations.  Lexer  emphasizes  such  a  ii4e 
of  origin  for  the  teratoid  mixed  tumors  of  the  abdominal  cavity  (se;§§ 
11'7,  1;{1,  and  147). 

Literature. 

{The  Complex  Teratoid  Ci/.sis  and  Tumors.) 

Ahrens:  Fotalinklusion  iin  Mcsokolou.    Laugenbecks  Arch.,  64  Bd.,  1901. 
&-rno>6.:  Beliaarte  Polypen  dor  Rachen-MundhOlile.    Virch.  Arch.,  Ill  Bd.,  1888. 


H 


i 


TERATOID    Tl.MOHS    AND    CYSTS.  497 

&.schoft':  C'ysteii.    Eri;rl)ii.  d.  allii.  Path.,  ii.,  1897(Lil.1. 

Beck:    I'datoiu  d.  lly popliysis  ctTcliii.     Zcitsclir.  f.    lli-ilk.,   1S83. 

Birch-Hirschfeld:   Nicnnucsrlnvulsle.     Ik'itr.  v.   7Avii\v\\   xxiv..  1898. 

Borst:  Die  aiii;rli.  Gcsclnvulsic  cl.  Sacmlrci-ioii.     C'bl.  "f.  ulli,r.    Patli.,  ix.,   1S98   (FJt.); 

Sakraltumor  iiiit  liiniart.  J^au.     Bcitr.  v.  Ziesjlcr,  xxxi.,  1902. 
Bostrom:  Piali- Epidt'iinoide,  DLTinoiile  u.  Japdhic  u.   duralc  Dmiioidi'.     C'lil    f   all" 

rath..    ]S(t7(Lit.). 
3raun:  Die  Doppciliilduiigcn  u.  die  aiigeb.   Gcschwiilstc  d.   Kicu/liciii.'ci^cud     l.cip. 
[       zig,  ix&l 

3uzzi:  Anircl).  Gcschwulsteder  Sacrococcyiicalgegciid.     Virch.  Aich..  lfi!»  Ud..    1SS7. 
Christian:  Doriiioid  Cvsts  and  Tcratonuuii  of  the  AnI.  ]\Ii'(iiasI.     .Idur.  of  JNIcd    IJos 
j      lit:  12. 
Oangschat:  Dcrmoidcvstom  u.  Tcratome  im  ]\It'diastiiiiiiii  aiiticuiu       15    v    ]5ruii>;    ."{y 

i!d  ,  lil(l3  (Lit.). 
■:berth  ;  Intraciaiiii-llc.'^  Tciaioin.     Yircli.  Arcli.,  1.");}  Bd..    1S<)S. 
ilkehorn:   DciiiHiidcystcii  dcs  .'Mcdiastiiiimis.     Aicii.  f.  kliii.  Cliir.,  .")('.  I'.d.,   ISits. 
ilng-elken:  Kinhr.  Diuscngcsclnviilst  d.  ^.'icrciigL'gcnd.  JScitr.  v.  Zicglcr,  xxvi.,  ISUU. 
:nglander:  Teratoma  omeuti  niajoris.    Cbl.  1'.  allg.  J*atli.,  xiii.,  1902. 
'rank:  Tumor sacralis  (Teratomm.  Dcniioid- u.   Flimmercysten).     Prag.  mcd    Woch 

lMt4. 
I'urstenheim-    Kicmengangauswuchse  in,   Knorpcl-Gerust.     Jahrh.   f.    KinchTJirilk., 

lennig':  Congcn.  Sacraltumoren.     Beitr.  v.  Zicglcr,  xxviii,,  190(1 

lertzog-  and  Lewis:  Embryonal  Keual  Adeuosarcoina.     Aiuer.  Joiirii.  of  M«d.  Sc, 

astreboff:  Angeb.  Geschwiilste  iuder  Gegeud  dos  Kreuzbeins.     Viich.  Arch  ,  99  Bd 

■■       INS,-). 

ores    Dcrmoidcyste  mit  Cyslosarkom  der  Lunge.     Virch.  Arch.,  18:!  Bd.,  189:5. 

'lirmisson:  Chirurg.  Kraukiieiteu  angeb.  Urspiungs,  Stuttgart,  1899. 

iiolaczek:  Dermoid  d.  Ovariums  mil  Bauchfellmetastasen.      Virch.  Arch.,  75  Btl., 

!      1879. 

ioslowski:  Hodensack-Tcratom.     Virch.  Arch.,  148  Bd.,  1897. 

exer-  Tcratoide  Geschwiilste  d.  Baudiholde.      Arch     f.   klin.   C'hir.,   (il   Bd.,  1900; 

'     Fr»tale  Inclusioneu  in  der  Bauchhohle.     lb.,  63  Bd.,  1900. 

■inser:  Sacralteratome.     Beitr.  v.  Bruns,  xxix.,  1901. 

aisena:  Tuinori  misti  dclla  reg.  sacro-coccigea.     B.  v.  Zicglcr,  xxxii.,  1902. 

liarchand:  Sacraltnniorcm.     Eulenburg'.s  liealencyklop.,  xxv.,  1899. 

iiarwedel:  Kin  Fall  vou  persistirendem  Urmund  (Hctroanal  cntwickcltcs  T)arMi.>;ti'ick 

I     mit  sacnilcm  After).     Beitr.  v.  Bruns,  xxix..  1901. 

[iddeldorpf:  Angeb.  Geschwitlste  in    der   Gegeud   dcs  Krcu/.bcins.     Vircli.  Arcli., 

I     100  15(1  ,  1885. 

|;ontgomery:  A  Terat.  of  the  Abdom.  Cavity.     Jour,  of  Exp.  :\Icd.,  iii.,  1898. 

i'oussaud:  Dcs  inclusions  foetales.     These  de  Paris.  18()1. 

iasse:  Gencse  der  sacrococcygealen  Tcratome.     Langcnb.  Arch.,  4.")  Bd.,  IS'CJ. 

vto:  L'chcr  cinen  congenit.  behaarten  Bachenpolypcn.   Virch.    Arch.,    ILI  Bd.,  1SS9. 

enzo:  Teratoma  sacralc.   A.  per  le  Sc.  JMed  ,  xxvii.,   1903. 

immer:  '!(  ratnlo-ische  3Iittlicilungcn.     Cbl.  f.  allg.  I'ath.,  i.,  1890. 

itschl:  An-cli.   Sacralgescliwulste.      Beitr.  v.  Bruns,  viii.,  1892. 

oUeston:  Adcno-cliondrosarcoma  of  tlie  Mediastinum.    Jour,  of  Patli.,  iv.,  1890. 

iixer:  Teratom  im  III.  Ventrikcl.     Beitr.  v,  Ziegler,  xx.,   1896  (Lit.);  Dermoid   d. 

I    llarnhlase.     lb.,  xxxi.,   1902. 

^hmidt.  Bezich.    d.    Steissgeschwulste  zu   d    Steissdriise.     Virch.    Arch.,  102  Bd., 

i    1888;  ZwciFalie  von  Gcschwiilstcn  inderGegend  des   ydnvanzbeincs.     Arb.  a.  d. 

I    <liir.  UnivfT.sitatspoliklinik  v.  B.  Schmidt,  Leipzig,  1891. 

fegenbeek  van  Heukelom    Tum    cong.  du  cou.     Kev.   de  trav.   du   Lab.,    Bocr- 

I    liaave,  1899. 

!;olpe-  Anircb.  Gcsclnv.  d.  Krcuzstcissbcingegcnd      Dcut.  Zeitschr.   f.   Chir.,  .">0  I5d.. 

is..,0.      ^ 
•^rassmann  u.  Strecker-  Ein  Teratom  im  reclitcn  Scitcnvcntrikcl.     \  inli.    Arch., 

:     l<l>SBd. 

J.tton:  Dermoids  or  Tumors  containing  Skin,  Hair,  Teeth,  etc.,  Lon(h)n,  1889. 
'rchow:  Teratoma  mvomatodes  mcdiastini.     Virch.  Arch.,  r)3Bd..  1871. 
"eigert:  Teratom  d.  Zirbcldriise.     Virch.  Arch.,  G5  Bd.,  187"). 

ilms:  Dermoidcysten   u.  Tcratome.     Dent.  Arch.  f.  klin.  Mcd.,  ',:,  B(L,  1895(1.11.): 
Die  Mischgcschwulsteder  Niere,  Leipzig,  1899;  der  Vagina  u.  der  Cervix,  Leipzig, 

I    1900. 

j    See  also  §^  120  and  147. 

'  :V2 


CHAPTER  IX. 

Disturbances  of  Development  and  the  Resultin; 
Malformations. 


P 


I.  General  Considerations   Regarding  Disturbances  of   Developnnt 
and  the  Origin  of  flalformations. 

§  129.  After  the  copulation  of  the  sexual  nuclei  has  taken  place.ihe 
development  of  the  embryo  proceeds  by  a  progressive  division  of  in  lei 
and  cells,  associated  with  which  there  arise  in  an  orderly  manner  esp(,ial 
groupings  of  cell-complexes  and  dififereutiation  of  the  same  into  espc.'ial 
tissues  and  organs.  The  multiplication  of  the  cells,  as  well  as  the  dt  3I- 
opment  of  individual  cell-groups  into  especial  organs  and  parts  ol:he 
body,  depends  upon  intrinsic  causes,  and  is  controlled  by  the  chara«(ir- 
Istics  which  the  embryo  has  received  through  the  transfer  of  the  inh  it- 
able  i:)aternal  or  maternal  characteristics  at  the  moment  of  the  uuioiof 
the  sexual  nuclei,  which  are  to  be  regarded  as  the  carriers  of  inlierit;)le 
characteristics.  It  follows,  therefore,  that  the  characteristics  of;he 
species  as  well  as  the  especial  peculiarities  of  the  given  indi\idual  aiin 
general  already  j) redetermined  in  the  germ,  and  the  development  0;!he 
embryo  proceeds  essentially  under  the  control  of  innate  moulding  fo  [es. 
Nevertheless,  this  development  is  not  accomplished  without  the  inflii;ice 
of  environment,  in  that  the  embryo  of  necessity  receives  its  nourishi|;nt 
from  the  maternal  organism,  and  at  the  same  time  is  exposed  to  mecliii- 
cal  influences  on  the  part  of  its  membranes  and  of  the  uterus.  I2se 
infiueuces  may  therefore  operate  to  modify  the  development  of  the  fcjis. 

In  every  species  of  animal,  man  included,  both  the  bodily  formiHi 
the  configuration  of  the  organs  present  a  particular  type,  which  experiace 
has  shown  constantly  to  recur,  and  which  is  therefore  looked  upc.  as 
normal.  If  more  or  less  marked  departures  from  this  type  occur,  v\fdi 
can  be  referred  to  a  more  or  less  marked  abnormal  course  of  the  i  'w- 
uterine  development,  the  condition  is  designated  as  a  congenital  'al- 
formation.  When  the  departure  from  the  normal  structure  is  ny 
marked,  so  that  the  affected  individual  is  grossly  malformed,  it  is  sp:eu 
of  as  a  monster. 

According  to  common  usage,  the  term  malformation  ig  usnalVip- 
plied  only  to  anomalies  in  the  form  of  the  body  as  a  whole,  or  to  s'gle 
parts  of  it  which  present  to  external  inspection  rather  striking  deparires 
from  tlie  normal.  It  is  nevertheless  entirely  correct  to  use  this  ten, for 
pathological  conditions  of  intrauterine  origin,  which  consist  not  so  ijicli 
in  an  abnoi-mal  change  in  form,  but  rather  in  an  incomplete  or  f:ilty 
organization  of  the  affected  part  or  organ.  i 

A  malformation  affecting  a  single  individual  is  known  as  a  sigle 
malformation  or  single  monster;  one  made  up  from  two  iudividusis 
termed  a  double  malformation  or  double  monster. 

Malformations  may  owe  their  orif/in  to  either  intrinsic  or  extrinsic  cises, 

4ys 


CAUSES    OF    -AlALFOiniAlIONr 


499 


As  intrinsic  causes  maybe  cousitk'ivtl  all  siich  as  already  rxisi  iit 
the  <renii.  so  that  iii  the  developineut  ot'  the  embryo  mallormations  may 
aiise  spontaneously  without  the  aid  of  exlrinsie  intluenees,  WIumi  sueli 
a  inallormation  oeeuis  lor  the  lirst  time  in  a  family,  it  must  1h'  iej:;ai(led 
as  upriiiiort/  (/rnii-rari(iti<nt.  This  may  be  explained  in  one  of  two  ways: 
either  one  or  both  of  the  sexual  nnelci  entering-  into  union  may  have 
U'en  abnormal,  or  both  may  lia\e  been  normal,  but  from  their  union  a 
\arietv  has  arisen  which  from  one  point  of  x'ww  is  to  be  re-^Mrded  as 
ll.atholoo-ieal  (ef.  §  17). 
it  is  also  possible  that 
ilisturbanees  in  the  proc- 
esses ("f  fertilization  can 
lu'ive  rise  to  pathological 
Variations. 

If  a  similar  malfor- 
jiiiation  has  already  oe- 
i.'urredin  the  parent,  the 
['juse  may  l)e  rey:arded  as 
|>ne  of  inhrritam-e.  If  the 
liialformat ion  appearinj; 
is  a  peculiarity  which 
was  not  present  in  the 
i)arents,  but  did  show 
tself  in  more  remote 
luieestois,  while  want- 
ing in  the  intermediate 
links,  the  phenomenon 
(s  designated  as  atavism. 

As  primary  jiciin- 
iariations  api)eai-  t h e 
i^  a  111  e  malformations 
jvhieh  are  also  inherit - 
fil)l( — that  is,  only  those 
Inalformatious  are  in- 
iieritable  which  origi- 
lilly  appeared  as  i)riniary 
jrerm  -  variations.  To 
m\\  inheritable  malfor- 
Inations  Ix-long  the  in- 
j'rease  in  the  inunber  of 

lie  lingers  and  toes  (i)olydactylisni),  malformations  of  tlie  hands  and 
jeet,  abnormal  liairiness,  hareli)),  and  certain  i)atliologieal  conditions  of 
ihe  nervous  system,  as,  for  exam])le,  multiple  lii>i(»mata  of  thr  i)eripln*ral 
ler^•es. 

Under  extrinsic  causes  of  malformal  ions  ar<- to  be  considcrrd  rspe- 
ially  concmsion.  prcssurr,  disturbaiins  in  thr  suppln  of  o.njiii  n  amt  unurish- 
'fi^nt,  and  infections. 

!  Concussions  of  the  uterus  nnty  in  all  probaltility  <lin'ctly  damagr  the 
ImhrA-o  at  a  very  eaily  stage.  At  a  later  stage  of  (h-velopnu-nt  the  harm- 
iil  effects  of  tiaunni  are  ])rol)abiy  more  often  to  be  sought  in  a  tearing 
k»oseof  the  egg  and  in  decidual  Ineincnrhages,  wherelty  the  nonrishnuMit 
k  the  embryo  is  disturbed.  It  is  evi<lent  that  haMnorrhages  from  <»fher 
jauses,  also  changes  in  and  contaminations  of  the  maternal  blood,  as 
(D  infectious,  and,  further,  imthological  conditions  of  the  uterus  itM-lf. 


Fig.  371.— Malformation  of  the  head,  due  to  ndbi-slons  of  the  mem- 
branes to  the  frontal  retricm  (Ilrm  adherence  of  placenta  to  utenw). 
r(,  Membranous  sac  inclosini,'  a  vasi-ular,  spongy  tissue  cont^ilnlntr 
numerous  cysts;  h,  eye;  c.  lip;  (/,•  funnel-shap<'(l  depression  llmnl 
with  mucous  membninc;  . ,  left,  c,,  rljfht  ala  nasi;  /,  connwtlv**- 
tissue  bands.    Reduced  (ini--fuurtli. 


500 


DISTURBANCES  OF  DEVELOPMENT. 


nuiy  have  a  harmful  influence  upon  the  developing  egg;  yet  all  thest 
conditions  probal»ly  lead  more  often  to  the  death  of  the  foetus  and  thti 
expulsion  of  the  egg  than  to  the  development  of  a  malformation.     Infecj . 
tious  diseases  of  the  mother  may  be  transmitted  to  the  foetus  and  giv(|  j 
rise  to  their  characteristic  changes  in  the  latter.     An  abnormal  pressurd  i 

from    the    uterus    or  its  memi 
branes    may    be   exerted    upoij : 
the    embryo,     especially    whei! 
there   is   a  deficient  amount  o 
amniotic   fluid ;    and   malforinaj  ; 
tions   of    the   extremities    (Fig| 
374),    in  particular,    not   infrej 
quently  show  evidences  of  press!  i 
ure  having  been  exerted.  ! 

From  the  anatomical  finding; 
in  many  malformations  it  api 
pears  that  pathological  condii 
tions  of  the  amnion  may  exerj 
a  damaging  influence  upon  th,' 
embryo  and  give  rise  to  diflferen! 
forms  of  malformations.  j 

This  may  be  brought  aboiijv 
through   abnormal   adhesions  be  | 
tween  the  embryo  and  the  amnioni 
as  well  as  by  pressure  of  the  anl  \ 
nion  npon  the  embryonal  anlag<]  '■ 
Even  at  the  birth  of  the  chili 
adhesions  in  the  form  of  bauc,.j 
and  threads  (Figs.  371,/;  373! 
may  not   infrequently  be   den  j 
onstrated,  and  their  connectio  ■ 
with    the    malformed    parts    :' 
such  as  to  leave  no  doubt  that  they  stand  in  a  causal  relation  to  tr 
malformation.     Such  adhesions  may  give  rise  to  severe  malformatioi! 
of  the  cerebral  (Fig    371)  or  of  the  facial   (Fig.  372)   portions  of  tij 
head.     Not  infrequently  portions  of  the  extremities  are  snared  off  b 
amniotic  bands  (Fig.  373),  and  may  be  completely  amputated  and  the. 
absorbed.  j 

To  what  extent  these  adhesions  of  the  amnion  with  the  foetus  are  l! 
be  referred  to  primary  adherence  and  iutergrowth,  and  to  what  exteit 
to  inflammatory  processes  of  later  occurrence,  is  yet  a  disputed  questioij 
Xot  infrequently  the  adhesions  at  birth  are  no  longer  visible  and  tl!  i 
affected  part  presents  only  a  scar-like  appearance  (Fig.  372).  j 

According  to  Dareste  and  Geoffroy  St.-Hilaire,  an  abnormal  tightuC; 
of  tlie  amnion  may  easily  exert  a  harmful  influence  upon  the  embry' 
An  abnormal  closeness  of  the  cephalic  cap  of  the  amnion  may  cause  tl' 
malformations  known  as  auencephalia,  exencephalia,  cyclopia,  and  ceb 
cephalia  or  arrhincephalia  (§  134);  while  an  abnormal  tightness  '; 
the  caudal  cap  may  give  rise  to  sireuomelia  (§  138).  Further,  the  clC' 
malformations  of  the  anterior  abdominal  and  thoracic  walls  (§  13())  a.< 
also  associiited  with  a  faulty  development  of  the  amnion ;  still  the  latt;- 
condition  is  often  not  so  much  the  cause  as  it  is  a  concomitant  of  tl! 
malformation,  which  may  be  the  result  of  a  variety  of  causes,  and,  i' 
deed,  is  often  to  be  regarded  as  a  spontaneous  or  primary  malformatioj 


Fig.  37:i.— Malformation  of  the  face,  caused  by  amni- 
otic adtiesion  and  pressure.  Asymmetry  of  the  face,  a. 
Malformed  nose;  h,  h,,  rudimentary  lid-clefts;  c,  c,, 
clefts  in  the  upper  lip  and  alveolar  process  of  the  upper 
jaw;  d,  intermaxillarj^t)one  with  prominent  lip;  c, 
oblique  facial  Assure  closed  by  scar  tissue  so  as  to  form 
a  groove. 


CAUSES    OF    :vrALF()iniATI().\S. 


501 


Tlie  period  at  which  the  injurious  iulhienee  is  active  varies  f^reatly, 
ami  consequently  so  does  the  extent  of  the  (lanuij;;e  (h)ne  by  it.  The 
earlier  the  damage  occurs,  the  greater  the  extent  oi  the  injury.  :\lal- 
formations  in  the  narrower  sense  of  the  term  arise  chielly  during  the  lirst 
three  months,  during  the  ])eriod  when  the  body  and  its  individual  i)arts 
are  develo])ing  their  jjroper  forms.  Damage  to  the  fo'lusal  a  latrr 
periotl  occasions  cliangv.s  which  arc  more  vlosclij  aUicd  to  t/io.sc  ((ciiiilrrtl  aflrr 
birth. 

fc^ome  malformations  are  typical— that  is,  they  always  appear  in  the 
same  f(n-m;  while  others  again  are  Mholly  atypical,  so  that  the  most 
astonishing  anomalies  of  form  may  arise.  The  latter  are  for  the  gi-eater 
part  the  result  of  extrinsic  harmful  influences  operating  secondarily, 
while  the  former  maybe  regarded  as  owing  their  origin  chietly  to  in- 
triusic  causes,  although  external  influences  nmy  also  cause  typical  mal- 
formations. 

Geoffroy  St.-IIilnire  ("Hist.  gen.  ct  partic.  dcs  anoiiuilics  dc  IdiL^aiii/.atioii  (tlic/ 
rhouime  ct  Ics  aiiimaux,"  Paris,  1832-37)  discards  ciitircdy  tlic  tcacliiiiii-  of  a  i)riinary 
abnormality  of  tlie  gaxm  {Haller  san\  ^yulslo)r),  and  attributes  arrcsis  (it  dcvclopim-nl 
purely  to  mechanical  intiuences.  Pdniiin  {"Vwivr^wch.  fiber  die  Eutsteliuiig  der  Miss- 
bildungen,"  Berlin,  1860)  agrees  witli  lum  on  tiie  whole,  although  lie  admits  tiie  possi- 
bility of  a  primary  abnormality.  He  produced  malformations  in  liens'  eggs  by  means 
of  temperature  variations  and  by  varnishing  the  shells.     Ddre.ste  ("  Heciierches  sur  la 


Fig.  373.  Fk;.  374. 

Fig.  373. -Hand  stunted  by  amniotic  adhesions;  ring-finger  snared  olT;  middle  and  index  lingers  grown 
together  and  distorted.    Uediiced  onc-sixtli. 

Fig.  374.^Hand  stunted  and  deformed  by  pressure;  thumb  absent;  hand  flattened;  great  bending 


and  shortening  of  the  fores 


III 


•d  one-llftli. 


I   production  artiticielle  des  monstruosites,"  Paris,  1877)  made  similar  e.xiieriiiieiils  ami 
'    produced  malformations  due  to  arrested  development  by  keeping  the  eggs  in  a  vertical 
.    position,  by  varnishing  the  shells,  by  raising  the  temperature  above  4.5    C,  and  also  liy 
irregular  warming  of  the  eggs. 

Very  recently  L.  Clerhirh.  Fol,  Wurifiisky,  Richter,  Hour,  and  Schnltze.  have  in  par- 
ticular carried  on  experiments  in  this  line,  aiid  have  attempted,  with  partial  success,  to 


502  DISTURBANCES    OF   DEVELOPMENT. 

produce  malformations  in  chicken-embryos  through  the  localized  influence  of  radiant 
heat,  variations  of  temperature,  varnishing  the  eggs,  changes  of  position,  injuries, 
removal  of  a  portion  of  the  white  of  the  egg,  and  by  agitation.     Roiix,  experimenting 
on  frogs'  eggs,  found  that,  after  destruction  of  one  of  the  tirst  segmentation-spheres,  i 
the  other  continued  to  develop  and  formed  the  half  of  an  embryo,  thus  demonstrating 
that  each  of  the  tirst  two  segmentation-cells,  corresponding  in  their  position  to  the  right  i 
and  left  body-halves,  contains  within  itself  the  anlage  material  for  the  corresponding  i 
half  of  the  body.     But  since  the  body-half  which  is  wanting  may  later  be  replaced  by  i 
subsequent  development  from  the  undestroyed  lialf,  and  a  whole  structure  be  produced,  \ 
eacli  half  must  also  possess  the  power  of  producing  also  the  other  half.     According  to  ; 
investigations  by  Ileiiitska,  IJrieficJi,  Morgan,  Wilson,  and  others,  the  first  two  or  even 
tile  tirst  four  segmentation-cells  in  tritons,  teleosts,  ascidians,  and  echinoderms  possess  ' 
the  power  of  forming  an  entire  embrj'o. 

SchuKze  experimented  on  the  eggs  of  amphibia;  these  normally  always  assume 
such  a  position  that  the  darkly  pigmented  protoplasmic  substance  of  lighter  specific  ; 
gravity  lies  above,  the  heavier  clear  protoplasm  rich  in  yolk  granules  lies  below.  By 
placing  the  eggs  in  an  abnormal  position  and  preventing  their  return  to  the  normal ! 
position  malformations  may  be  produced,  the  degree  of  malformation  standing  in  direct  i 
relation  to  the  size  of  the  angle  formed  by  the  line  of  gravity  and  the  abnormally- ! 
placed  axis  of  the  egg.  By  turning  the  egg  through  an  angle  of  180°  in  the  two-cell  i 
stage  a  double  monster  is  regularly  produced.  The  same  turning  in  the  eight-cell  i 
stage  causes  a  complete  cessation  of  development.  These  disturbances  arise  from  dis- 
placements consequent  upon  the  sinking  of  the  heavier  and  a  rising  of  the  lighter  con-! 
stituents  of  the  egg. 

According  to  investigations  by  0.  Hertioifi,  the  eggs  of  axolotl,  when  kept  in  a  0.7- ' 
per-cent.  solution  of  sodium  chloride,  undergo  a  pathological  development,  which  is' 
confined  to  the  central  nervous  system  in  the  region  of  the  head  and  trunk.  If  frogs.j 
eggs  are  left  before  fertilization  for  one  to  four  days  in  the  uterus  of  the  dead  femald 
and  are  then  fertilized,  there  are  formed,  besides  normal  embryos,  'various  malformatioubl 
due  to  defective  development,  for  example,  spina  birtda. 

Recent  studies  have  shown  that  monsters  and  malformations  may  be  produced  by; 
Uoentgen  irradiation  of  fertilized  ova  or  of  either  ova  or  spermatozoa  before  fertiliza-! 
tion.  Gilman  and  Baetjer  found  that  the  eggs  of  amblj^stoma  developed  abnormalljl 
under  Roentgen  irradiation,  the  embryos  showing  no  mouths.  Chicks  developed  ir 
exposed  eggs  presented  malformations  of  the  occipital  region  and  extremities  and  ii 
the  distribution  of  the  feathers.  Bardeen  found  that  in  frogs  injury  to  the  spermatozof 
by  Roentgen  rays  caused  the  development  of  monsters  from  eggs  fertilized  by  sucl 
damaged  spermatozoa. 

Literature. 


{Malformations  and  Their  Origin.) 

Ahlfeld:  Berichte  und  Arbeiten   aus  der  geburtshiilfl.  Klinik  zu  Marburg,    1885-86 

Die  Missbildungen  des  Menschen,  Leipzig,  1880,  1882. 
Ballantyne:  The  Diseases  and  Deformities  of  the  Foetus,  1.  and  ii.,  Edinb.,  1893,  1895' 
Barfurth:  Ucber  oryanbildende  Keimbezirke  u.  klinstliche  MissbiliUingen  d.   Amplii 

bieneics.     Anat.  Hefte,  Wiesbaden,  1893;  Regeneration bei  Embryouen.     llandb.  d 

Entwickeluugsl.,  iii.,  1903. 
Braun,  C. :  Neue  Beitr.  z.  Lelire  v.  d.  amniotischenBandern,  Wien,  1862. 
Charrin  et  Gley:  L'influence  teratogene  des  prod,  microbiens.  Arch,  de  phy's. ,  IS'.Mi 
Dareste:  Recli.  sur  la  production  artif.  desmonstruosites,  ii.  ed.,  Paris,  1894. 
Davaine:  JNIonstre,  Monstruosite.    Dictionn.   encyclop.,  abgedr.  in  L'oeuvre  de  Da 

value,  Paris,  1889. 
Delag'e:  Structure  du  protoplasma  et  Ics  theories  de  I'heredite,  Paris,  189o. 
Driesch:  Entvvickelungsmechan.  Studien.  Zeitschr.   f.  wiss.  Zool. ,  53,  55  Bd.,  1891 

l,Si)2;  Anat.  Anz.,  vii.,  1892. 
Duval:  Teratogenic.     Path.  gen.  publ.  p.  Bouchard,  i.,  Paris,  1895. 
Endres:  Etitwickelungsmechanik.     Eulenburg's  Jahrb.,  vii..  1897. 
Endres  u.  Walter:  Anstichversuche  an  Eiern  von  Rana.     Arch.   f.   Eutwickelungi-; 

luccli.,  ii.,  1895. 
Fischel:  r!(u:cinvart.  Stand  der  ex  perinientellen  Teratologic.     Verb.  d.  D.  path.  Ges.. 

v..  1902  (Lit.). 
Folcl  Warynsky:  Rech.  exp.  sur  la  cause  de  quelques  monstruosites.  Recueil  zool 

Suisse,  i.,  1883. 
Eorster:  Die  ISIisshildungen  des  Menschen,  Jena,  1865. 
Foster:  Z.   Kenntniss  d.  Hemmungsmissbildung  d.  unt.    Korperhiilfte..     I.-D.,ri 

burg,  1903. 


^.|a 


f 


CLASSIFICATIOX    OF    .MALFOini ATIOXS.  503 

Gerlach.  Prodnctiim  v.  Zwergbildungen  im  Iliilinerci.     Biol.  Cbl..  ii..  188.3;    Neue 

i\Ii>tlio(lcn  auf  (k'lu  Gebiete  der  exporimeutellon  Eiubryolos'ie.    Ib.,vii.,  1889:  Auat. 

All/.,    1SS7. 
Giaccomini:  Anomalies  de  devolojip.  dc  rcinbryon  liumain.    Arch.  ital.  do  Biol.,  i\., 

ISS8;  xviii.  aud  xix.,  1892;  xx.,  JSij:^;  xxiv.',  1895;  luHueuce  de  I'uir  mrCtiC'.     lb., 

xxii..  1894. 
Guinard:  Precis  de  teratologie,  Paris,  1S98. 

Gurlt:  Literatiir  Tiber  .Alissgeliiirleii.     Viicli.  Arch.,  71   I'.d.,  1.S7S. 
Hertwig:  .Missl)iidimgen   u.   .^Ichrrachliihlmimii,   wdchc    diircli    St(")nmg  dcs   ersten 

Eutwickelungsprocesses  liervorgeruleii  wenhn.      llandli.  d    Kiitwickeluufislclire 

I.  Jena.  190;i. 
Hirst  and  Piersol:  Human  Monstrosities,  Pliiladelphiu,  1891. 
His:  XVber  mechanische  Grundvorgange  thierischer  Formbiidung.     Arch.  f.   Anat.. 

isy4. 
Israel;    Angol).   Spalten    d.   Ohrlappchens,   ein.    Beitr.   z.   Vererbungslciiri'.      Virch. 

Arch.,  119  Bd.,  1891. 
Kirmisson:  Ohir.  Kraukbeiten  angcb.  Ursprungs,  Stuttgart,  1899. 
Kollniann-  Die  Kbrperform  menscbl.  normaler  u.  pathol.  Embryonen.     Arch.  f.  An., 

1SS9. 
Kiistner:   Ueber    eine    noch    nicht    bekannte    Entwickeluugsursache    anipvitirender 

aniniotischer  Fiiden.     Zeitsckr.    f.    Geb.,    xx.,    1891;  Die   Pathologic  des  Fdtus, 

[Stuttgart,  ISSS. 
Lannslongue  et  Menard:  Affections  cougenitales.     I.  Tete  et  con,  Paris,  1891. 
Marchand:  Missbildungen.     Eulenburg's  Kealencyklop.,  xv.,  1897  (Lit.). 
Mitrophanow :  Teratogeuet.  Studien.     Arch.  f.  Entwickehingsmech.,  i.,  1895. 
Morian:  Die  schrage  Gesichtsspaltc.     Arch.  f.  kliu.  Ciur. ,  1887. 
Moser:  Missbild.  durch  amniotisclie  Bander.     Prag.  med.  Woch.,  1894. 
Otto:  ]\[onstrorum  sexceutorum  descriptio  anatomica,  1844. 
Panum:  Zur  Kenntniss  d.    physiol.    Bedeutung  d.   angeb.    Missbildungen.      Virch. 

.Vrch..  73Bd.,  1878. 
Piersol:  Teratology.     Ref.  Handbook  of  Med.  Sc,  2d  ed.,  1903. 
Richter:  Ueber  die  experimentelle  Darstellung  der  Spina  bifida.     Anat.   Anz.,  iii., 

1SS8. 
Roux:   Zur  Entwickelungsmeclianik  des    Embryo.      Zeitschr.    f.    Biol.,    xxi.,    1886; 

Ki'instliclie  Hervorbringung  hall)er  I'knbryonen  durch  Entfernuug  einer  der  beideu 

ersten  Furchungskugeln,  u.  Waclistliuinscnlwickelung  der  fchlenden  Kiirperhalftc. 

Virch.  Arch.,  114  Bd.,  1888;  Die  Entwickeluugsniechanik  der  Organismen,  Wien, 

1890:    Ueb.    das   eutwickelungsmechanische   Vermogen   jeder   der   bciden    crsien 

Furchungszellen  des  Eies.     Verb.  d.  Anat.  Ges.,  vi.,  1892;  Ueber  die  Speciticatii)n 

der   Furchungszellen   unci    liber  die   bei    der   Postgeneration    und    Kegcueration 

anzunehmenden  Vorgiinge.     Biol.  Cbl.,  xiii.,  1893;  Die  Methodcn  zur  Erzeugung 

halber   Froschembryoneu.      Anat.    Anz.,   ix.,    1894;  Einleitung   zum  Archiv    fiir 

Entwickelunsgnieclianik  der  Organismen.     Arch.  f.  Entwickeluugsmechanik,  i., 

1894. 
Schultze:  Die  Bedeutung  der  Schwerkraft  fur  die  organische  Gestaltung,  sowie  iiber 

(lie  init  Hiilfe  der  Schwerkraft  mogliche  kunstliclie  Erzeugung  von  Doppelmiss- 

l)il(lungen.     Verb.   d.   Phys.-med.  Ges.,   28  Bd.,   1894;  Eutwickelungsgeschichte, 

bipzig,  1896. 
Taruffi:  Storia  della  teratologia,  i.-viii..   Bologna,   1881-96;   Sull'  ordinamento  della 

tiratologia.     K.  Accad.  delle  Sc.  dell'  1st.  di  Bologna,  1890,  1898. 
Virchow:  Descendenz  u.  Pathologic.     Virch.  Arch.,  103  Bd.,  1880. 
Wiedersheim :  Der  Ban  des  ^lenschcn,  Fieiburg,  1893. 
Ziegler;  Ki>nncn  erworlx'iie  pjitliolog.  Figenscliaftcn  vererbt  werden  u.  wie  entstehen 

crliliclK!    Krankheiten    u.    Missbildungen.     Beitr.    z.    jiathol.  Anat.,  i.,   1886;  Die 

ncuesten  Arb.   iiber  Vererbuug  u.   Abstammungslehre,  u.  ilire  Bedeutung  fiir  die 

Patiiologie.     lb.,  iv.,  1889. 
Ziegler,  K.':  Zur  Postgenerationsfrage.     T.  D.,  Freiburg,  1901. 
Fur  literature  of  Malformations,  see  Anat.  An/,.,  i.-xxvii.,  1880-1907;  and  Cbl.  f.  allg. 

Path.,  i-xviii.,  1890-1907. 

§130.  Single  malformations  may  be  convciiiciitly  (li\  idcd  iiilo  live 
grou])s,  accofdiii.u-  lo  \hv  kind  of  cIkuijuc!  which  (•hjii-actciizrs  them. 

As  arrests  of  development  or  monsters  due  to  defective  develop- 
ment (monstra  per  defectum)  may  he  chisscd  in  llic  liisl  ])l!icr  ;dl  tho.se 
malformations  in  which  the  whole  or  ;i  part  of  tlie  ho<ly  is  ahnornudly 


504  DISTURBANCES    OF    DEVELOPMENT. 

small  and  imperfectly  developed  {hypoplasia),  and  also  those  malforma- 
tions characterized  by  the  complete  absence  or  very  great  stuutiug 
{agenesia  or  aplasia)  of  individual  organs  or  parts  of  the  body. 

If,  in  the  case  of  parts  or  organs  of  the  body  which  are  normally 
formed  by  the  nnion  of  anlage  which  are  originally  separated,  such 
union  should  fail  to  take  place  as  the  result  of  a  primary  or  secoudaryi 
disturbance  of  growth,  the  arrest  of  development  may  show  itself  iu  the 
form  of  clefts  and  reduplications.  Thus,  for  example,  imperfect  develop- 
ment of  the  plates  forming  the  anterior  body- wall  gives  rise  to  clefts  in 
the  median  line  of  the  thorax  and  abdomen ;  a  failuie  of  union  of  the 
maxillary  processes  of  the  first  branchial  arch  with  each  other  or  with 
the  nasal  process  of  the  frontal  bone  gives  rise  to  clefts  iu  the  face. 
Defective  union  of  the  bilateral  portions  of  the  female  genital  traci 
results  in  a  more  or  less  extensive  reduplication  of  the  uterus  or  vagina. 

When  the  anlage  of  two  organs  lie  near  to  each  other,  these  may 
under  certain  conditions  become  united  so  as  to  produce  a  coalescence  or 
adhesion  between  two  organs  or  parts  which  should  normally  be  sepa 
rated.     For  example,  the  kidneys  at  times  may  be  more  or  less  united,! 
and  the  eyes  may  be  more  or  less  comi^letely  merged  into  a  single  orgaii. 

rialformations  due  to  excessive  growth  (monstra  per  excessum) 
are  characterized  in  part  by  abnormal  size  of  individual  parts,  and  in  i)ait 
by  au  increase  in  number  of  the  same.  For  example,  an  extremity  or  ai 
portion  of  one,  as  a  finger,  may  reach  an  abnormal  size  (partial  ffiaut 
growth),  or  the  whole  body  may  be  involved  in  the  abnormal  growtl 
{general  giant  growth).  An  increase  in  number  occurs  particularly  iu  tbej 
case  of  the  mammary  gland,  spleen,  adrenals,  and  fingers.  Additional! 
glandular  organs  are  designated  accessor  1/  or  supernum<rarii  organs.  1 

As  malformations  due  to  an  abnormal  disposition  of  organs  (mon-i 
stra  per  fabricam  alienam)  are  designated  by  Forster  certain  anomalies^ 
of  the  internal  organs  of  the  thorax  and  abdomen,  which  are  character-; 
ized  by  au  abnormal  position  of  the  organs,  and  in  part  also  hy  change.-: 
in  the  relation  of  individual  parts  to  each  other.  In  this  class  belong^■ 
the  condition  known  as  situs  transversus — that  is,  the  transposition  of  the 
thoracic  or  abdominal  organs,  or  of  both.  Further,  various  defects  i 
the  heart  and  great  vessels  may  also  be  classed  here,  though  it  should  " 
noted  that  these  are  more  properly  regarded  as  arrests  of  development. 

A  fourth  group  of  malformations  includes  those  characterized  by 
displacement  of  tissues  and  by  the  persistence  of  foetal  formations 
already  mentioned  in  §§  12G  and  128. 

Finally,  as  a  fifth  group  may  be  classed  those  malformations  ex 
hibiting  a  mixture  of  the  sexual  characteristics,  known  ;is  true  am 
false  hermaphroditism.  True  hermaphrodites  possess  both  male  and  femal 
sexual  glands;  false  hermaphrodites  are  unisexual,  but  the  remaiudei 
of  the  sexual  apparatus  does  not  correspond  to  the  sexual  gland,  or  then 
is  a  simultaneous  formation  of  organs  belonging  to  both  the  male  and 
female.  A  part  of  these  malformations  are  arrests  of  development 
others  are  to  be  regarded  as  cases  in  which  from  the  original  bisexn;i 
anlage  the  organs  of  both  sexes  have  developed,  whereas  normally  tin 
anlage  of  one  sex  undergo  a  reti-ograde  change  instead  of  developing;, 
and  persist  only  in  a  rudimentary  form. 

§  131.  Double  monsters  (monstra  duplicia)  are  malformations  con 
sisting  of  two  individuals;  if  both  twins  are  developed  {symmetrica 
twins)  they  are  always  of  the  same  sex  and  are  united  to  each  other  ii 
tlu^  same  portions  of  the  body;  the  duplicated  portions  are  usuall\ 
ecjually  developed  {equal),  but  wne^wa/ forms  also  occur  iuM'hich  onetsvii 


J 


CLASSIPICATIOX    OF    M  ALIOH.M  A'lK  ).\S.  505 

is  stunted  in  its  devolopnuMit.  A sjun metrical  forms  jilso  occur  in  wliich 
one  twin  i-enmins  wholly  rudimentary  and  is  deiuMidcnl  ii|)oii  ihc  olhor 
ioY  W^wwXvxWow  [parnsitic  double  mousier).  Oltcii  il  is  Imji/dufctl  iw  the 
other  or  included  Mithiu  it  (see  §  127). 

All  double  nion.sfers  arise J'roiii  one  egg  and  have  a  eoiinnoii  eiiorion.  In 
the  t'orniatiou  of  sjimmetrieal  double  iiioii.stfrs  two  separate  embryonal  an- 
lage  ai-e  ])i-ol>al)ly  formed  from  one  ,i;e''r.iinal  vesicle,  and  these  in  their 
growth  l)lend  with  each  other  to  a  grealc  or  less  extent,  but  a.  dnplica- 
lion  or  a  s])littini;-  may  also  occur  within  a  single  anla,i;e,  and  this  ])rocess 
H'curs  particularly  in  the  anterior  reduplications  Avliich  can  also  be  pro- 
lueed  experimentally  in  animals.  The  genesis  of  the  rudimentary  ani/m- 
metrical  Ucins  occurs  chiefly  in  the  manner  described  in  §  127  (Teratonuita). 

Tlie  cauuvs  of  a  duplication  of  the  embryonal  a  nlac/e  in  a  single  fieruiinal  reside  are  not 
ivnowu.  According  to  T*}--^,  double  and  multiple  monsters  arise  tlirough  the  abnormal 
impregnation  of  an  ovum  witli  two,  three,  or  more  spermatozoa ;  but  other  observa- 
ions  \Born)  indicate  that  ova  fertilized  by  two  or  more  spermatozoa  do  not  develop. 
.Vccordiug  to  MarcJmnd,  the  doubling  of  the  anlage  is  to  be  referred  to  conditions  exist- 
iig  before  the  beginning  of  segmentation,  either  to  conditions  within  the  egg  before  fer- 
ili/;ition,  or  to  the  fertilization  itself.  Wiede)n(tnn  and  Wetzel  iiold  the  opinion  tiiat  tlie 
irigin  of  double  monsters  dates  from  the  moment  of  impregnation,  and  is  due  to  the 
ertilization  of  ova  containing  two  germinal  vesicles  by  two  spermatozoa. 

Gerlach  produced  double  monsters  (anterior  duplication)  from  hens'eggsby  varnisli- 
ing  these  before  inculxiting,  leaving  free  only  a  Y-shaped  spot  in  the  region  of  the  prim- 
tive  streak.  Inasnuicii  as  he  only  rarel}'  succeeded  in  obtaining  sucli  results,  it  is  pos- 
;il)le  lliat  these  malformations,  which  not  infrequently  occur  in  chickens,  were  acci- 
iental.  ,9f//w/^^(;  obtained  double  monsters  by  turning'froRs' eggs  during  the  two-cell 
taee  through  an  angle  of  180°  (cf.  §  129).  Spemann  Avas  able  to  produce  double- 
icaded  embryos  of  tritons  by  constriction  of  the  embryonal  anlage  before  the  closure 
)f  the  medullary  plate  to  form  the  medullary  groove;  also  by  a  median  constric- 
inn  in  the  two-celled-  and  blastula-stage.  Born  succeeded  in  uniting:  together 
lortions  of  the  larvre  of  amphibia,  not  only  of  the  same  kind,  but  also  of  dillerent 
pecies,  genera,  and  families  {JRana  esculenta  with  Bombinator  if/neiis,  and  with 
.I'riluH).  The  conditions  were  most  favorable  for  union  in  the  case  of  larvaj  of  about 
!  mm.  length.  Not  only  the  external  coverings  of  the  body,  but  also  the  anlage  of 
I'rgans  (liver,  intestine,  heart-tube),  were  blended  into  a  united  organ,  the  unicm  being 
ompleted  through  specific  tissue  of  the  same  kind.  From  all  these  experiments  the 
iinclusion  may  be  drawn  tliat  double  monsters  maybe  produced  from  a  normal  egg 
liroiigli  secondary  influences,  and  that  neighboring  embryonal  anlage  may  grow  one 
ito  tlie  other.  On  the  other  hand  lies  the  possibility  that  especial  conditions  within 
lie  egg  before  fertilization  may  be  the  cause  of  the  duplication.  According  to  Srhidtze, 
his  may  possibly  lie  in  the  presence  of  two  nuclei  or  of  two  spindles,  or  in  an  over-ripe 
oiulition  of  the  egg  with  a  tendency  to  fragmentation  into  two  halves,  wliich  divide 
liortiy  before  fertilization.  Tlierefore  a  normally  fertilized  ovum  in  the  two-cell 
tage  may  be  brought  through  some  influence  (as  in  the  experiment  of  Schultzc)  to  the 
ormation  of  two  individuals. 

Literature. 

{Double  Mounters. ) 

whlfeld:  Die  Missbildungen  des  Menschen,  Leipzig.  1880,  1882. 

;Oru:  Furchungen  des  Eies  bei  Doppelbildungen.     Breslauer  iirztliche  Zeitschr.,  1887; 

Ueber  Dopi)elbil(lungen  beim  Frosch.     lb.,   1882;   Ueljcr  Verwachsungsversuche 

nut  Anipiiibienlarven,  Leipzig,  1897,  ref.  Dent.  med.  Woch.,  1898,  8.  12(5. 
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isiio,  18(56. 
'ebierre:  La  theorie  de  la  monstruo.site  double.     Arch,  de  phys.,  ii.,  1890. 
'ebierre  et  Dutilleul:  Monstres  doubles  du  genre  synote.     Arch,  de  nhj's..  ii.,  1890. 
ol:  l!eeh<rclies  sur  la  fecondatidu,  etc.,  1879. 
orster:  Die  .Missbildungen  des  Menschen,  .Jena,  1805. 
eoffroy  Saint-Hilaire :  Hist.  gen.    et   partic.    des  anomalies  de  I'organisat.  chez 

riioinme  et  les  aniniaux,  Paris,  1832-37. 
erlach,  L. ;  Uel)er  die  Entstehungsweise  der  vorderen  Verdoppelung.     Deut.  Arch., 


506  DISTURBANCES  OF  DEVELOPMENT. 

f.  kliu.  Med.,  43  Bd. ;  Die  Entstehungsvveise  der  Doppelmissbildungen,  Stuttgart 

1883. 
Gschier:  Thoracopagus  tetrabradiius  aequalis.     Prag.  med.  Woch.,  1892. 
Klaussner:  Mehrl'achbildungea  bei  Wirbelthiereu,  Miinchen,  1890. 
Kormann :  Ueber  Icbeude  DoppelmissbilduDgen  der  Neuzeit.     Scbmidt'.s  Jalirb. ,  cxliii  i 

1  sci). 
Iiochte:    Kin  Fall  von  Doiipclniissbildungen.     Bcitr.  v.  Ziegler,  xvi.,  1894. 
Marchand;   !\Iissliil(lungen.     Eulciiburg's  Realencyklop.,  xv.,  1897. 
Myschkin:  /wiiliiigsschwangx'rschalt  u.   augeb.   Missbikhmgen.     Virch.   Arch.    10^ 

Bd.,  1887. 
Panum:  Untersuchungen  liber  die  Entstehung  der  Missbildungen,  Berlin,  1860;  Zui 

Kenutniss  d.  phy.s.  Bedeutung  d.  Missbilduugeu.     Virch.  Arch.,  72  Bd.,  1878. 
Raiiber.  Die  Tlieorie  der  excessiven  Monstra.     Virch.  Arch.,  71,  73,  74  Bd.,  1877-78. 
Schafer:  Ueber  einen  Dicephalus.     Beitr.  v.  Ziegler,  xxvii.,  1900. 
Schultze,   O. :   Ueber  die  Bedeutung  der  Schwerkraft,  etc.      Verh.  der  phys.-med 

Gesellsch.,  28  Bd.,  1864;  Arch.  f.  Entwickelungsmech.,  1.,  1894;  Entwickeluug  d 

Doppelbildungeu.     Cbl.  f.  allg.  Path.,  x.,  1899. 
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1901. 
Spermann:  Exper.  Erzeug.  zweikOpfiger  Embryonen.     Sitzber.   d.   phys.-med.  Ges. 

1900;  Entwickelungsphysik.     Stud,    an    Tritonen,     A.    f.    Entwickelungsmech.! 

XV.,  1902  u.  xvi  ,  1903,  u.  Zool.  Jahrb.  vii.,  1904.  , 

Wetzel:  Drei  abnorm  gebildete  Eier.     Anat.  Anz.,  xviii  ,  1900.  i 

Wiedemann:  Entstehung  d.  Doppelbildungen.     Virch.   Arch.,   138  Bd.,  1894  (Lit.)' 

See  also  §  129. 

i 
II.  The  Different  Forms  of  Malformations  in  Man.  ! 

I.  Arrests  of  Development  in  a  Single  Individual.         : 

(a)  Arrest  of  the  Development  of  the  Entire  Emhnional  Anlagr.        \ 

1 
§  132.   An  arrest  in  the  development  of  the  entire  embryonal  aniag 

manifests  itself  in  two  ways.  If  the  distnrbance  is  vei-y  marked,  a  fur 
ther  development  of  the  embryo  is  impossible,  and  it  either  dies  at  oiic 
or  becomes  stunted,  and  after  a  certain  time  perishes.  If  the  disturbaiic 
is  less  severe  there  develops  a  normally  formed  foetus,  but  it  remain 
small  and  stunted — that  is,  a  dwarf  is  formed  (nanosomia  or  micrc 
somia).  I 

A  dead  foetus  is  in  the  majority  of  cases  expelled  together  with  ill 
membranes  (abortion).  In  other  cases  in  which  the  embryo  for  soni; 
cause  or  other  remains  stationary  in  development,  the  egg  may  remaii 
for  weeks  or  even  months  in  the  uterus  and  increase  in  size,  so  thatthei 
arises  a  disproportion  between  the  size  of  the  embryo  and  of  the  egj 
According  to  His,  the  first  changes  after  death  are  shown  in  a  marke 
swelling  of  the  central  nervous  organs,  leading  to  changes  in  the  coi 
figuration  of  the  head.  Later  there  occurs  an  infiltration  of  the  tissu* 
with  wandering  cells,  the  boundaries  of  the  organs  become  indistinc 
llie;  eiiliie  embryo  becomes  cloudy  and  soft,  the  su])erficial  structmi 
iiidistiiici,  and  the  embryo  finally  becomes  completely  dissolved.  A 
cording  lo  Jlerlet  and  Engel,  the  wandering  cells  infiltrating  the  tissij 
arise  in  llie  embiyo  itself,  and  indeed  from  its  own  blood. 

When  a  fuilus  well  advanced  in  development  dies  and  remains  wi 
the  maternal  oj-gaiiism  there  may  result  the  formation  of  a  lithopsedioi 
This  occurs  nn)st  fre<|uenlly  in  the  abnormal  situation  of  the  ovum  knew] 
as  extrauterine  pi-egnancy,  in  which  the  embryo  lies  in  the  peritone 
cavity,  in  a  tube,  or  in  an  ovary.  If  the  foetus  dies  at  such  an  advanci; 
stage  of  development  that  it  cannot  be  absorbed,  it  may  be  carried  with; 
the  maternal  organism  for  years.     Not  infrequently  its  form  is  perfect  | 


LITIIOP.EDIOX. 


507 


:)reserve(l  (Fig.  375),  and  the  Avhole  fcrtus  becomes  inelosed  in  a  connec- 
ive-tissne  membrane.  In  other  cases  the  feci  us,  in  the  course  of  time, 
)econies  converted  into  a  i)artially  lluid  mass,  Mhich  contains  the  osseous 
emaius,  as  Avell  as  fat,  clioh'sterin,  and  i»i<;-ment,  and  is  snirounih'd  1)>- 
I  tihrous  capsule.  Lime-salts  are  usually  deposited  botli  in  the  newly 
ornied  membranes  as  well  as  in  the  i)ortions  of  tlu>  feet  us  I'emai  nine;, 
uul  for  this  reason  the  foetus  is  known  j?fi  a  "stone-child"  or  "]>etrilied 
•hiUl." 


.a-'^ 


S. 


Fig.  375.— LitliopsBdion,  entirely  inclosed  in  connective-tissue  membranes  (removed  from  abdominal 
;arity  liy  oi»>ration  two  years  after  beginning  of  pregnancy).  Extrauterine  pregnancy  caused  by  embryo 
jreaking  ttirough  ttie  uterine  portion  of  a  tube  into  tlie  abdominal  cavity.    Reduced  to  one-third. 

I  According  to  the  condition  of  the  foetus  there  may  l)e  distinguished 
'liree  chief  forms  of  lithopiedion  (Kiichenmeister).  In  the  lirst  the 
■anmmified  foetus  may  be  easily  shelled  out  from  the  calcified  uuMubi-anes 
lithocfh/pho.s).  In  the  second  form  the  tortus  Ix'comes  adherent  to  the 
iiembranes  at  various  points  which  Ijecome  calcitied,  while  the  other 
>ortions  become  mummitied  (Uthoccli/phopmlion).  In  the  third  form  the 
ijetus  is  discharged,  through  the  rupture  of  the  memljranes,  into  liie 
'•eritoneal  cavity,  and  later  becomes  encrusted  with  lime-salts  {IHIiopmUon 
II  the  narrower  sense). 

,  The  long  retention  of  a  ripe  or  even  older  fd'tusicithin  the  uterus  {inixKcd  l<ih<n)  is  rare, 
;<it  may  occur  (1)  in  an*  accessory  horu  of  the  uterus,  (2)  in  interstitial  pregnancy,  (3) 
,fter  rupture  of  the  uterus. 


508  DISTURBANCES    OF    DEA  ELOPMEXT. 

Literature. 

{Disturbances  of  Development  of  the  Embryo.     Lithopwdion. ) 

Bandl:  Die  Extnuitcnuschwangerschaft.     Handb.  d.  FraiK-nkranklieiten,  ii.,  StiittLrart 

1S8G. 
Eberth:  3Iyxom  des  Chorion.     Viich.  Arch..  39  Bd.,  1867. 
Engel:  Rlickbildungsvorgange  an  abortiven  Embryoncn.     Beitr.   v.  Zicgler,  xxviii.; 

liXIO.  "  ■ 

Giaccomini.  Entwickelungsanomal.  d.  menschl.  Embryo.    Ergebu.  d.  Anat.,  iv.,  If^OJ 

and  loc.  cit    i^  130. 
His.   Fiaucu  d.  path.  Embryologic.     Internat.  Beitr.  Festschr.  f.  Virchow,  i.,  1891. 
Kleinwachter :  Alissed  Labor.     Eulenbiirg's  Realencyklop.,  v.,  1895  (Lit.). 
Kroemer;     Zur  Kcnntn.  der  Lithopiidien.     Miinch.  med.  Woch.,  1900. 
Kiichenmeister:  Ueber  Lithopadion.     Arch.  f.  Gyn.,  xviii.,  1881. 
Mall:  I'athologv  of  Early  Human  Embryos.     Johns  Hopkins  Hosp.  Rep  ,  ix.,  1900. 
Marchand-  Bail  der  Blasenmole.     Zeit.  f.  Gebh.,  38  Bd.,  1895  (Lit.). 
Martin.    Extranterinschwangerschaft.     Eulenb.  Realencyklop.,  1895  (Lit.). 
Miiller.  H. .  Ueber  den  Ban  der  Molen,  Wiirzburg,  1847.  , 

Virchow:  Die  kranldi.  Geschwiilste,  i.,  1863.  ' 

Wallenstein :  Beitr.  z.  pathol.  Embryologie.     Inaiig.-Diss.,  Freiburg,  1897. 

(&)  Defective  Closure   of  the  Cerebrospinal    Canal  and   the  Accompanj/in' 
Malformations  of  the  Hervous  System. 

§  133.  Defective  closure  of  the  vertebral  canal  leads  to  the  mall 
formations  known  as  rachischisis  or  spina  bifida.  If  the  defect  in  thi 
vertebral  column  is  open  so  tluit  at  the  bottom  of  the  cleft  the  bodies  o! 
the  vertebrae  covered  by  membrane  are  seen,  the  malformation  is  ordij 
narily  termed  rachischisis.  When,  at  the  site  of  the  defect,  there  is  see! 
a  i^rotruding  sac,  the  malformation  is  usually  designated  spina  lifida,  oj 
more  correctly  spina  bifida  cystica ;  though  to  this  formation  the  nam« 
rachischisis  cystica  or  hydrorachis  cystica  may  also  be  apj)lied. 

In  rachischisis  totalis  (hoJorachischisis)  (Fig.  376)  the  bodies  of  tl 
vertebrae  form  a  shallow  groove  opening  posteriorly,  and  usually  covere 
by  a  thin,  transparent  membrane ;  in  rare  cases  rudiments  of  the  spin;r 
cord  are  still  jiresent  in  the  form  of  whitish  bands  and  lines.  In  th; 
manner  there  occurs  a  total  or  partial  amyelia.  The  defect  involv«i 
principally  the  motor  tracts  and  centres,  as  well  as  the  columns  <j 
Clarke  and  the  lateral  cerebellar  tract,  while  the  spinal  ganglia  are  devej 
oped  (Manz,  Leonowa,  K.  and  G.  Petren),  and  may  send  sensory  fibnj 
iuto  the  membranous  masses  of  the  spinal  groove.  j 

The  delicate  membrane  which  lines  the  furrow  and  covers  the  duil 
mater  lying  beneath  it  upon  the  bones  is  the  ventral  portion  of  tit 
si)inal  pia  mater.  A  part  of  the  nerve-roots  may  have  undergone  deyei 
opment,  arising  either  from  rudiments  of  the  spinal  cord  or  from  spin: 
ganglia. 

Partial  rachischisis  (meroraehischisis)  involves  usually  the  sacrolun 
bar  or  the  upper  cervical  region,  while  the  intervening  portions  of  tl 
vertebral  column  ai'e  only  rarely  the  seat  of  malformations.  The  dorsij 
surfaces,  with  the  overlying  dura  and  pia  mater,  of  the  bodies  of  tlj 
vertebrie  whose  arches  remain  rudimentary  are  covered  for  the  great<i 
])art  l)y  a  mass  of  velvety  vascular  tissue,  which  contains  rudiments  I 
llie  siiinal  cord  (the  area  mcdullo-rasculosa,  von  Recklinghausen),  thouj. 
the  amount  of  this  tissue  may  be  very  small  or  may  even  be  wholly  war. 
iiig.  To  the  outside  of  this  tissue  layer,  which  is  not  everywhere  equal 
abundant  and  which  diminishes  at  the  sides,  there  comes  next  a  delicatj 
tiaiisparcnl,    vasculai-  nicmbranc  Mhich  represents  the  continuation 


I 


SPINA    HiyiDA. 


509 


thr  i)ia  iiiator  covered  ^vitll  epitlielium  (~o//ff  cpillHlio-scromi);  and  uexl, 
ontside  of  this,  a  zone  of  epidenuoidal  tissne  somovliat  lliinncr  llian 
normal  skin,  and  often  eovei-ed  -with  many  liairs  (zoint  <lrr)n(ilic(i),  sepa- 
latinii-  the  reddenetl  central  area  from  the  normal  skin. 


S^v 


Fk;.  376— Craniorachischlsis  with  total  absence  of  the  brain  and  spinal  ooid.  Tlie  base  skull  is  cov- 
ered with  ragged  membranous  masses,  the  open  spinal  furrow  with  a  delicate  membnme  (pia  mater). 
Kypholordotic  curvature  and  shortening  of  the  spinal  column.    Reduted  one-hi\tli. 


Spina  bifida  cystica  or  rachicele  (rar/ti.HcJii.si.s  ci/stira)  occurs  in  tliife 
ji-liief  forms:  mjjelomeninffocele,  meningocele,  and  mi/eloet/Ntocele.  Accord- 
ling  to  its  site  there  may  be  further  distinguished  a  cervical,  dorsal,  lum- 
jl)iir,  lumbosacral,  and  a  sacral  spina  bifida.  Jn  general,  a  spina  bifida 
jis  characterized  by  the  development  of  a  fluctuating  tumor,  which  is  in 
nost  cases  visible  externally  (Fig.  377)  on  the  jxislerior  aspect  of  the 


(^^ 


I  Kir..  37T.-Spina  bifida  ; 
fie  size  of  a  pigeon's  egL' 
ear  on,  while  at  thcsume 


cralis.     (AftiT  Froriep  and  Forster.)    (Virl  of  nineteen  years,  bom  with  a  tumor 
I  er  ttie  uppiT  siicral  and  lower  luiiib.ir  regions,  wliidi  enlarged  fn)in  the  sixth 

uie  club-feet  developed. 


ipinal  column  (.spina  hijida posterior);  but  inslances  also  occur  in  whicli 
■  lie  sac  itrojccts  anteriorly  from  llu-  sjiiiial  ('■.iwA  (spiiKi  hijiiht  mihrior), 
,nd  othcis  ill  which  it  is  so  small  that  it  is  coveicd  uith  noinial  skin 
nd  is  not  visible  externally  {.spina  bifida  occalla). 

Myelomeningocele  appears  most   ircipiciiily  as  a  .spinti  hijiila  hnnho- 


510 


DISTURBANCES    OF    DEVELOPMENT. 


sacmlis,  and  usually  forms  a  tumor  varying  iu  size  from  that  of  a  nut  to 
that  of  an  apple  and  increasing  in  size  after  birth,  iu  the  region  of  the 
lower  lumbar  and  upper  sacral  vertebriie.  It  is  covered  either  by  smooth 
or  scar-like  skin,  or  may  be  devoid  of  skiu  on  its  summit  and  there  cov- 
ered by  a  reddish,  mucosa-like  tissue  (area  medullovasculosa).  The 
portion  uncovered  by  skin  may  be  drawn  in,  like  a  scar.  Iu  rare  cases 
there  may  be  no  external  tumor  (spina  bifida  occulta),  the  site  of  the 
cleft  being  indicated  only  by  a  more  marked  growth  of  hair  or  by  a 
depression. 

On  opening  the  sac,  which  is  composed  of  the  arachnoid  (Fig.  378,  e) 
and  the  pia  (/,  /,),  while  the  dura  (g)  does  not  extend  over  the  dorsal 
portion  of  the  sac,  it  may  be  seen  that  the  lower  end  of  the  spinal  cord 
(6,)  is  drawn  outward,  and  that  the  cavity  of  the  sac  is  crossed  by  nerve- 
roots  (/,  /, ).  Occasional  uerve-roots  (h )  may  also  spring  from  the  columns 
of  the  cord  (hj  in  its  course  through  the  sac. 

According  to  these  findings  there  is,  therefore,  an  accumulation  of 
fluid  iu  the  meninges,  a  hydromeningocele  (hydrorachis  externa  circum- 
scrii^ta),  which  is  combined  with  a  pro- 
lapse of  the  spiual  cord,  a  myelocele.  At 
the  site  of  the  protrusion  the  vertebral 
arches  are  defective,  and  this  defect  may 
reach  as  far  as  the  hiatus  sacralis. 
Smaller  defects  may  involve  only  one  or 
two  vertebrffi. 

Dorsal  and  cervical  meningoceles  are 
much  more  rare  than  the  lumbosacral. 
The  defect  in  the  vertebral  arch  is  usu- 
ally confined  to  one  or  two  vertebrae. 
The  spinal  cord  is  here  involved  in  the 
meningocele  in  so  far  that  portions  of  it 
are  drawn  outward  in  the  form  of  a  band 
or  cone. 

Hydromeningocele  spinalis  arises 
from  a  hernial  piotrusion  of  spinal  arach- 
noid due  to  a  localized  collection  of  fluid 
in  the  sul>arachuoidal  si^ace.  It  may  oc- 
cur In  the  first  place  at  the  upper  end  of 
the  spinal  column  in  the  case  of  a  cleft  of 
the  upper  cer^-ical  vertebne,  at  the  same 
lime  with  hernia  of  the  brain  in  the  oc- 
cipital region.  More  frequently,  how- 
ever, it  occurs  iu  the  sacral  region,  where 
the  hernial  protrusion  takes  place  either 
through  a  defect  in  the  vertebral  arches 

and  bodies  or  through  the  hiatus  sacralis,  or  between  vertebral  arches,, 
or  through  inteivertebral  foramina.  In  the  majority  of  cases  the 
dura  takes  no  ])ait  in  the  foiination  of  the  sac,  but  views  differ  upon 
this  point,  and  l)y  many  Miiteis  (Ilildebrand)  a  dural  sac  is  described. 
Tlirougli  a  progiessive  accumulation  of  fluid  the  sac  may  attain  a  very 
large  size.     Small  meningoceles  may  l)e  concealed  in  the  deep  tissues. 

According  to  the  direction  of  tlie  hernial  protrusion  there  may  be 
distinguished  a  meningocele  posterior  and  a  meningocele  anterior,  the  latter 
taking  place  tiirougli  a  defect  in  the  bodies  of  the  vertebrae  (rachischisis 
anterior). 

riyelocystocele  or  hydromyelocele  (syringomyelocele)  takes  its  origin 


Fig.  378.— Myelomeningocele  sacralis  in 
sagittal  section,  a  little  to  the  left  of  the 
median  line.  (After  von  Recklinghausen.) 
a,  skin;  b,  hi,  spinal  cord;  c,  area  me- 
dullovasculosa; d,  cranial,  d,,  caudal 
polar  groove ;  e,  arachnoid ;  /,  pia,  some- 
what separated  from  the  arachnoid;  /,, 
portion  of  pia  mater  turned  over ;  g,  dura 
mater;  h,  recurrent  roots  of  the  fourth 
lumbar  nerve ;  i,  radix  anterior ;  i,,  radix 
posterior  of  the  fifth  lumbar  nerve,  run- 
ning free  through  the  arachnoidal  sjic ;  k, 
sacral  nerve-roots  between  the  arachnoid 
and  pia ;   I,  fllum  terminale. 


RACITTSCTTTSTS.  51 1 

in  ii  dilatation  of  the  central  canal  of  the  spinal  cord,  as  a  result  of 
which  a  larc;er  or  smaller  ])ortion  of  the  cord  with  its  connecti\  el  issue 
envelopes  becomes  converted  into  a  cystic  tumor.  Tlie  duiu  is  usually 
wanting-  over  that  portion  of  the  sac  ]n-oti'udinc;  from  the  vertebra'. 

According  to  von  J\ecklinghausen,  tlu^  wall  of  these  sacs  is  formed 
essentially  of  the  inner  s})inal  meninges,  but  is  lined  on  the  interior  by 
a  cylindrical  epithelium,  and  has  at  some  part  of  its  inner  surface  an 
area  medullovasculosa — usually  on  the  ventral  side,  rarely  on  the  dorsal. 
Corresponding  to  this  condition  the  roots,  in  case  they  are  still  pre- 
served, spring  mostly  from  the  ventral,  rarely  from  the  doisal  outer  wall 
of  the  sac.     The  cavity  itself  is  crossed  neither  by  bands  nor  by  nerves. 

Myelocystoceles  occui-,  in  the  majority  of  cases,  in  latcMal  clefts  of 
the  vertebral  column.  They  show  a  tendency  to  becombiiH'd  )nth  (IrffTts 
and  asymmetries  of  the  bodies  of  the  vertehne,  and  thereby  often  with 
shortenings  of  the  trunk,  which  at  times  affect  only  the  dorsal  region,  at 
other  times  also  the  lumbar  region.  Very  frequently  there  exists  at  the 
same  time  an  exstrophy  of  the  abdomen,  bladder,  and  intestine. 

Myelocystoceles  are  mostly  covered  only  by  the  outer  skin,  but  are 
sometimes  concealed  deep  down  in  the  soft  parts.  They  ni:iy  further 
be  combined  witli  a  meningocele,  so  that  a  myelocystomeningocele 
arises. 

In  cases  of  rachischisis  there  sometimes  occurs  a  division  of  the 
spinal  cord  into  two  parts  (diastematomyelia),  most  often  in  tin;  case  of 
a  total  rachischisis,  in  which  indeed  the  rudiments  of  the  spinal  cord 
are  usually  only  indicated.  In  partial  rachischisis  such  division  is  more 
rare,  but  the  separated  strands  of  spinal  cord  are  better  developed,  and 
the  fibrous  and  bony  coverings  may,  at  the  beginning  or  end  of  the  cleft, 
send  dividing  septa  between  them.  Cases  have  occurred  in  which  each 
cord-half  possessed  an  H  -shaped  area  of  gray  matter. 

In  the  earliest  embryouic  period  the  Tiicdullaiy  groove  is  formed  by  tlie  develop- 
ment on  both  sides  of  the  median  line  of  •vvull-like  elevations  of  the  ectoderm  which  are 
designated  as  the  medullary  folds.  Through  the  converging  growtii  and  union  of  the 
latter  the  medullar}-  groove  is  closed  and  formed  into  the  medullary  canal.  Thereupon 
the  cell-masses  (primitive  vertebral  plates)  lying  at  the  sides  of  the  newly  formed  canal 
form  an  envelope  about  it,  which  gives  rise  in  the  first  place  to  a  membranous,  non- 
articulated  vertebral  column.  In  this,  at  the  beginning  of  the  second  montii,  there 
arise  discrete  cartilaginous  areas  from  which,  in  the  course  of  further  development,  tin; 
vertebral  bodies  and  arches  are  formed,  while  between  them  the  intervertebial  discs 
and  vertebral  ligaments  appear.  The  development  of  tiie  cartilaginous  vertebra'  is  not 
completed  until  the  fourth  month,  and  up  to  tliis  time  the  dorsal  covering  of  tiie  med- 
ullary tube  consists  of  the  united  portions  of  the  membranous  vertebral  C(ihnnn.  Tiie 
cartifaginous  constituents  of  the  vertebne  arc  in  the  course  of  development  replaced  by 
bone. 

The  oriyin  of  rncMscliisis  is  to  be  referred  to  agenesia  and  hypojdasia  of  the 
medullary  folds,  which  should  form  the  medullary  groove  of  tlie  vertebral  arcjies. 
The  agenesia  of  the  spinal  cord  is  also  to  be  dated  from  the  very  earliest  jx-riod. 
AVhetlier  it  is  a  primary  agenesia  predetermined  in  the  ficrm,  or  whether  extrinsic  in- 
jurious influences,  perhaps  toxic  substances  {Ihvtinij],  pressun;  from  without,  or  tiie 
inclosureof  fa'tal  membranes,  may  have  secondarily  checked  devel()i)ment  or  liave  de- 
stroyed parts  already  formed,  it  is  usually  dillicult  to  determine;  l)ut  the  symmetrical 
distribution  of  the  arrested  development  speaks  in  favor  of  the  former  view. 

In  cases  of  f^pimi  hifuhi  with  hernial  protrusion,  the  local  defect  a  in  the  hmnj  veriehriil 
column  and  th,  il,frtlr,'<l,r,h,j,,ii,i,t  (f  the  dura  mater,  which  is  usually  wanting  at  tiie 
site  of  the  jjidti  iisinn,  aic  to  lie  regarded  as  the  primary  condition.  The  growtli  of  the 
sac  may  be  ex II lain ed  as  due  tu  congestive  and  inflammatory  transudation,  and  the 
residue  of  inflanunatory  changes,  such  as  thickenings  and  membrauous  adhesions,  may 
often  be  demonstrated  in  the  pia. 

\on  UccJdin(]hauHen  \iiW\%  the  origin  of  myelocystocele  and  myelocystomeningo- 
cele to  a  deficient:  growth  in  the  long  axis  of  the  vertebral  column,  characterized  ana- 
--omically  by  shortness  of  the  column,  alisence  of  vertebne  or  parts  of  vertebrae, 
separation  of  wedge-shaped  bony  pieces  from  the  bodies  of  the  vertebne,  and  by  uiii 
lateral  defects  in  the  arches.     The  neural  canal,  then,  in  the  course  of  normal  develoj)- 


512  DISTURBANCES    OF    DEYELOP:\IEXT. 

mcnt,  becomes  too  long  for  the  vertebral  caual,  and  in  consequence  becomes  curled  or 
kinked,  and  there  is  a  tendency  to  a  partial  protrusion  of  the  medullary  tube  at  the 
point  of  sliarpest  bending.  Mavchand  believes  that  this  hypothesis  is  not  applicable  to 
all  cases,  and  Arnold  is  also  of  the  opinion  that  the  causal  relations  between  arrests  of 
development  in  the  muscle-plates  and  vertebral  anlage  on  the  one  hand,  and  those  of 
tlie  medullary  canal  on  the  other,  are  not  constant,  but  that  a  variety  of  harmful  influ-] 
ences  may  give  rise  to  one  or  more  of  these  anomalies.  Lucksch  emphasizes  particu-i 
lary  the  ellects  of  pressure  as  the  cause  of  myeloschisis,  but  without  excluding  otherl 
causes. 

According  to  0.  Hertwig,  the  ordinary  spina  bifida  is  an  arrest  of  development 
depending  upon  a  partially  prevented  closure  of  the  blastopore  ("Urmundspalte"). 

Literature.  t 

I 
{Malformations  of  the  Spinal  Cord  and  Vertebral  Column.)  I 

D'Ajutolo:  ('ontrib.  alio  studio  delle  varieta  numeriche  delle  vertebre,  II.,  Morgagni,, 

.\.\.\.,  1888. 
Albrecht,  P. :  Defect  der  drei  letzten  Sacral-  u.  saramtl.  Steisswirbel.     Cbl.  f.  Chir.,i 

1885.  I 

Arnold:    Myelocyste,    Transposition   von    Gewebskeiraen    u.    Sympodie.      Beitr.    v.] 

Ziegler,  xvi.,  1894.  "  , 

Beneke:  Diastematomyelie  mit  Spina  bifida.     Beitr.  z.  patli.  An.,  Festschr.  f.  Wagner,] 

Leipzig,  1887.  I 

Bohnstedt:  Spina  bifida  occulta.     Yirch.  Arch.,  140  Bd.,  1895.  | 

Borst;  Geschwiilste  d.  Sacralregion.     Cbl.  f.  allg.  Path.,  ix.,  1898  (Lit.)  \ 

Braune:  Die  Doppelbildungen  u.  d.  angeb.  Geschwiilste  d.  Kreuzbeingegend.,  Leipzig,] 

\xi\i.  ! 

Brunner:  Spina  bifida  occulta  mit  Hypertrichosis.     Yirch.  Arch.,  129  Bd.,  189^5.  I 

Curtius:  Spina  l)ifida.     Langeubeck's  Arch.,  47  Bd.,  1894.  ] 

Demme:  Bericht  iiber.  d.  Thatigk.  d.  Kinderspitals,  Bern,  1883;  Wien.  raed.  Blatter,! 

1SS4.  t 

Fischer  u.  Marchand:  Ueber  d.  lumbodorsale  Rachischisis  mit  Knickung  d.  Wirbel- 

siiule  uebst  3Iittheilung  eines  Falles  v.  Myelocystocele  lumbosacralis.     Beitr.  v. 

Ziegler,  v.,  1889. 
Forster:  Die  Missbildungen  des  Menschen,  1865. 

Hertwig:  Urmund  u.  Spina  bifida.     Arch.  f.  mikr.  Anat.,  39  Bd.,  1893. 
Hildebrand:  Spina  bifida  u.  Hirubriiche.     Deut.  Zeitschr.  f.  Chir.,  36  Bd..  1893  (Lit.).) 
Jacoby :  I)oppeli)ildung  des  embryonalen  Ruckenmarks.     Yirch.  Arch.,  147  Bd.,  1897.. 
Joachimstlial :  Spina  bifida  mit  "localer  Hypertrichosis.     Yirch.  Arch.,  131  Bd.,  1891 

(Lit.).  i 

Koch,  W. :  Beitr.  z.  Lehre  von  der  Spina  bifida,  Casscl,  1881.  | 

Kollmann:  Spina  bifida  u.  Caualis  neurentericus.     Yerh.  d.  Anat.  Gr^s.,  1893. 
Kroner  u.  Marchand:  Meningocele  sacralis  anterior.     Arch.  f.  Gyn.,  xvii.,  1881.         j 
Lebedeff :  Ueber  (.lie  Entstehung  der  Aneucephalie  u.  Spina  bifida.     Yirch.  Arch.,  8(1 

P.d.,  1881. 
Leonowa :  Anencephalie  mit  Amj-elie.     Neurol.  Cbl.,  1893. 

Iiucksch:  Exper.  Erzenguns;  d.  Rachischisis.     Z.  f.  Heilk.,  1904.  ] 

Manz:  l);is  Auucliindoscr  Missgeburten  Yirch,  Arcli.,  51  Bd.,  1870. 
Marchand:  Si>ina  liilidii.  Eulenburg's  Realencyklopjidie,  xxii.,  1899. 
Markoe  and  Schley:  The  Sacrococcygeal  Dimples,  Sinuses  and  Cysts.     Am,  Jour,  o; 

.M.-.l.  Sc,  l!)0-2. 
Muscatello:  Die  Angeb.  Spalten  d.  Schadels  u.  d.  Wirbclsilule.     Laugenb.  Arch.,  4, 

r.d  .  isi»4.  1 

Neumann:  Subkutane  Myelomeningocele.     Yirch.  Arch.,  176  Bd.,  1904.  \ 

Petren,  K.   u.   G. :  Nervensystem  bei  Anencephalie  u.  Amyelie.     Yirch.    Arch.,  15  j 

IJd.,  1S98. 
Pick:  Zur  A LTcncsie  des  Ruckenmarks.     Arch.  f.  Psych.,  viii.,  1878.  1 

V.  Recklinghausen:  Untersuchungen  iiber  Spina  bifida.  Yirch.  Arch.,  105  Bd.,  1886| 
Rex;  Einenthiimliche  Umbildungeu  des  normalen  Wirbeltypus.     Prag.   Zeitschr.   f! 

Heilk.,  vii.,  1835. 
Ribbert:  Spina  bifida  occulta.     Yirch.  Arch.,  133  Bd.,  1893. 
deRuyter:  Schiidd- u.  Riickgratssiialten.     Langeubeck's  Arch.,  40  Bd.,  1890. 
Saalfeld:  Spina  bifida  occulta'mit  Hypertrichosis.     Yirch.  Arch.,  137  Bd.,  1894. 
Sulzer:  Spina  l)ifitla  mit  Yerdoppelung  des  Ruckenmarks.     Beitr.    v.   Ziegler,   xii., 

1S!(3. 
Tarufii:  Delia  rachischisi.  Bologna,  1890. 

Virchow:  Yirch.  Arch.,  27  Bd.;  Die  krankh.  Geschwiilste.  i.,  1863. 
Wiedersheim :  Der  Bau  des  :\k'uschen,  Freiburg,  i.  B.,  1903. 


I 


MALFOH.MATIOXS    OF   THE    CRANiriM.  Slf? 

Wieting:  LVbcr  Spina  billda  u.  ZwciilK-ilung  d.  Kiickfinn.     liciir.   v.    J'.niiis,    \xv., 
J  SI)!). 

i;  1;U.  Faulty  development  of  the  cranium  and  the  associalfMl  dis- 
turbances of  cerebral  development  lead  lo  tliosc  nialloniiatioiis  known 
as  cnoiio.scliisi.s.  ((crania,  lionicrania,  mirrorrphalus,  amucrphalus,  c.vcucfph- 
alii.s,  ))ii<'mi<'rj>/iahi.s,  and  ccjihaJocrlr. 

Acrania  and  hemicrania  or  cranioschisis  aiv  the  results  of  an  aj^ene- 
sia  or  hypoplasia  of  the  bony  and  membranous  jwrtions  of  the  eraiiial 


Fig.  :iT9.— Anenceplialia  et  acrania.    Reduced 
one-half. 


I'm.  :mi.- Cranioschisis  with  Kxencephalia. 


vault,  which  arise  either  as  primary  disturbances  of  development  or  as 

the  result  of  harmful  extrinsic  intiuences  upon  the  cerebral  anlaj^e. 

In  acrania  l)oth  the  bony  portion  and  the  skin  of  the  cranial  vault 

(Fi.us.  ;)7{>,  lisl)   are  wholly  wanting,  the  surface  of  the  base  of  the  skull 

being  covered  only 
with  a  membranous 
\  ascular  tissue. 

If  the  defect  in 
the  cranial  vanlt  isas- 
•sociated  w  ilh  a  similar 
delect  intheveitebral 
ai'ches,  there  is  ])ro- 
dnced  the  condition 
known  as  craniora- 
chischisis  (  I'^ig.  ;57(i), 
in  wliich  the  spinal 
<•  o  1  n  m  n  is  nsnall_\ 
shortened  an«l  bent, 
the  head  in  cons«'- 
(pience  Ix'ing  drawn 
sharply  backwaid  and 
the  face  turned  uj)- 
\var<l.      Thi'ongh    a 

marked  bulging  of  the  eyes  with  deficient  development  of  the  forehead, 

these  malformations  may  resend)le  frogs  (frof/  Orfus). 


Fig.  3?1.— ['artial  agenesia  of  the  hones  of  the  cranium  in  anence- 
pnaJia.  a.  Defect ;  />,  squamous  portion  of  the  occipital  iKjne  ;  c,  parietal 
Done ;  tf,  frontal  hone.    Keduced  one-flfth. 


514 


DISTURBANCES    OF    DEA  ELOPMEXT. 


Ill  ItcmlcranUi  the  flat  bones  of  tlie  cranial  vanlt  have  undergone  more 
or  less  extensive  development  (Fig.  381,  h,  c,  d)  and  form  a  cranial 
cavity,  which  is  small,  in  that  the  flat  bones  of  the  vault  are  elevated 
but  a  short  distance  above  the  base  of  the  skull.  If  the  bones  of  the 
craniuni  Mliich  have  undergone  an  imperfect  development  yet  unite  with 
one  another  as  under  normal  conditions,  there  is  produced  a  simple 
microcephalus,  which  may  be  present  at  birth  or  develop  later,  as  the 
result  of  imperfect  development  of  the  skull. 

Acraniaand  hemicraniaare  often  associated  with  total  anencephalus, 
the  base  of  the  skull  being  co^'ered  only  with  a  membranous,  vascular, 
spongy  mass,  which  is  usually  composed  of  vascular  connective  tissue 
containing  scattered  haemorrhages,  and  showing  no  trace  of  brain  tissue 
or  only  undeveloped  rudiments  {area  cerebrovasculosa). 

In  other  cases  the  meninges  contain,  besides  cystic  cavities  and  gland- 
like remnants  of  the  medullary  plate,  also  more  or  less  developed  brain- 


FlG.  382.— Hydrencephalocele  occipital 


Fig.  SSo.— Encephalomenlufriii-eU'  nasofron talis. 


substance,  Avhich  usually  protrudes  through  the  defect  in  the  cranial 
vault,  giving  rise  to  exencephalus  (Figs.  380,  371).  The  hernial  masses 
are  eitlier  inclosed  only  by  a  soft  membrane  corresponding  to  the  inner 
meninges,  or  they  may  be  covered  also  by  external  skin. 

Willi  microcephalus  there  is  also  micrencephalus — that  is,  an  abnor- 
mal smallness  of  the  brain.  The  development  of  the  brain  is  also  usu- 
ally deficient,  or  certain  iiortions  may  be  lacking. 

If  the  cranium  is  in  general  closed,  but  presents  partial  defects, 
lK)rlions  of  the  cranial  contents  may  protrude  externally  in  the  form  of 
a  hernial  sac.  Such  a  condition  is  known  as  hernia  cerebri  or  cephalo- 
cele  (Figs.  382,  383).  Defects  of  ossification,  as  well  as  a  local  weaken- 
ing of  the  membranous  cranial  envelope,  are  doubtless  the  primary  cause, 
though  adhesions  of  the  meninges  with  the  amnion  may  also  be  a  cause 
(Sl.-ililaire).  The  dura  mater  is  wanting  over  the  extracranial  portion 
of  Die  sac  (Mnscatello). 

Tlie  size  of  Ihc  ])rotiiiding  sac  vaiies  greatly;  it  may  be  so  small  as 
to  be  found  only  after  careful  examination,  or  it  may  be  so  large  as  to 
apjnoach  the  bi-ain  in  volume.  If  only  tlie  arachnoid  and  pia  protrude 
as  the  result  of  a  collection  of  fluid  in  the  subarachnoidal  space,  the 
hernia  is  designated  a.  meningocele.  If  at  the  same  time  there  is  a  pro- 
trusion of  brain-sul)staiice,  it  is  known  as  meningoencephalocele.  A 
hernia  of  l)rain-substance  and  pia  without  a  collection  of  fluid  is  an 
encephalocele  ;  if  the  piotruding  brain-substance  contains  a  portion  of  a 
ventricli^  lilled  with  fluid,  it  is  designated  a  hydrencephalocele. 

Cerebral  liernias  occur  chiefly  in  the  occi])ital  region  (hernia  occipi- 
talis), close  above  the  foramen  magnum  (Fig.  3b2),  and  at  the  root  of 


DEFECTS    OF   THE    CH A XI I'M. 


515 


the  nose  (he)-)iia  si/ncipitalis).     In  the  latter  region  it  may  at  one  time 

involve   chielly   the   frontal   bone    {/i<-nii<(   nasofrontal  is,    Fiji;.    3S3),    at 

another  time  the  ethmoid  (hernia,  na.socthmoid- 

alis)  or  the  laehrymal  bone  {hernia  nam-orhit- 

alis).     ]More  rarely  hernias  oeeur  on  tlui  sides 

of  the  sknll  (^hernia  lateralin)  or  at  the  base  of 

the   sknll    {hernia   ba.sali.s).       The    latter    may 

l)ul*;e  toward  the  nasopharynx  (hernia  splieno- 

phanjnf/ea  ),  or  into  the  orbit  (hernia  .sj>hen<>-or/>it- 

X-  js      r  '  r  '■VMS\      <^'?/s),  or  into  the  fossa  sphenoiiiaxillaris  ( //r////a 

,n  ""  i  ^      sjihenomaxillarifi). 

In  the  case  of  a  central  hernia  tlui  brain 
may  be  either  normal  or  more  or  less  mal- 
formed. As  a  result  of  a  maiked  stnutinj;-  of 
development,  ijarticnlarly  in  the  region  of  the 
foremost  of  the  three  cerebral  vesicles,  the  cere- 
brum may  remain  single,  Avhile  at  the  same 
time  a  deficient  neparation  of  the  ocular  vesicles 
tal^es  place  {cycleneephalia  or  cijeloeephalia  of  St.- 
lu  severe  grades  of  this  form  of  disturbance  of  development 


Fig.  384.— Synophthalmos  or  cy 
elopia. 


lying  in  the  middle  of  the  forehead,  or 


Hilaire). 

only  one  eye  may  be  formed, 
two  eyes  united  together  may 
be  found  in  one  orbital  cavity 
(Fig.  384),  so  that  the  mal- 
formation may  be  designated 
cyclopia,  or  synophthalmus, 
and  as  arrhinencephalus 
(Kundrat).  The  nose  is  also 
stunted  (Fig.  384)  and  forms 
a  proboscis-like  cutaneous  tag- 
attached  above  the  eye,  and 
devoid  of  bony  foundation 
{ethmocephalia). 

When  the  eyes  are  sej^a- 
rate,  yet  abnormally  close  to- 
gether, the  nose  in  general 
may  be  normal,  though  very 
small  at  the  root  {cehocepha- 
li<i  I. 

In  the  more  severe  grades 
of  these  malformations  the 
ethmoid  bone  and  nasal  sep- 
tum may  be  wanting,  and  the 

I  upper  lii)  and  palate  may  be 

'  cleft  in  the  median  line,  on 
one  or  both  sides  (Kundrat). 
Ill  the  lighter  grades  the  fore- 
head is  merely  reduced  in  size 
and  sharply  pointed  like  a 
wedge. 

In  the  severe  forms  of 
these  malformations  the  cerebrum  consists  of  a  sac  (Fig.  385,/,  t),  oe- 

,  cupying  more  or  less  of  the  cranial  cavity  and  tilled  with  a  clear  lluid; 
at  those  points  where  the  sac  does  not  touch  the  cranial  wall  the  inter- 


O^'- 

|i.:^^i//^ 


Fig.  ;583.— Cranial  cavil y  of  a  synophthalmus  mlcrostomus 
opened  by  a  frontal  section  (seen  from  b<'liin(1).  ri.  Skin 
and  subcutaneous  tissue;  /),  cniniuin  ;  c,  dura  nialiT;  (<, 
tentorium;   r,  araclinoid;  /,  posterior  surface  of  tlie  ci-re- 

(/,  swolliMi  i-iIl^'  (pf  cerebral  sar  ;  /i,  siihiiraclinciidnl  space 
behind  tlic  ccrcliral  sac  ;  i,  cavity  of  tlie  cen-hral  sac.  c<mi- 
inunicatiiitr  Willi  Itn'  subarachnoidal  space  tliroinrh  the  en- 
larged transverse  Ilssmr;  /f.  section  tlirout'h  the  cori>oni 
quadriu'Muiiia  ;  /.  sfitimi  through  the  cerelK-llum  ;  m,  atlas. 
Seveii-ii-ntlis  natural  size. 


I 


510  DI8TURBAXCES  OF  DEVELOPMEXT. 

\  eiiiiij^  space  is  filled  bj^  fluid  distending  the  subaraclinoidal  space  (h). 
ill  the  less  marked  t'ornis  only  indi^•idual  portions  of  the  brain  are 
undeveloped,  those  parts  chiefly  affected  being  the  olfactory  lobes  and 
nerves,  the  cnri>us  callosum,  a  part  of  the  convolutions,  etc.  The  optic 
llialaini  are  often  blended  together.  The  chiasm  and  the  optic  tract  may 
be  altsent  <»i-  luesent.  The  corpora  quadrigemina  (A),  pons,  medulla 
ulthingata,  and  cerebellum  (I)  are  usually  unaffected. 

Till'  spinal  cord  and  brain  arise  from  the  medullary  canal.  In  that  portion  that  is 
1(1  hcfojno  the  brain,  tlie  neural  canal  changes  very  earl}-  into  three  vesicles.  The  most 
anterior  of  these,  the  forebrain,  throws  out  from  its  lateral  portions  the  primary  optic 
vesicles,  while  tlie  middle  portion  grows  forward  and  upward  and  divides  into  the 
fth  nrtiihahiit  ov  forebrain,  and  the  dienctpJudon  {thalamenceplKtlori)  or  tireeiihritin.  From 
the  former  are  developed  the  cerebral  hemispheres,  corpora  striata,  corpus  callosum. 
and  the  forni.x.  From  the  tweenbraiu  are  formed  the  optic  thalami  and  the  tloor  of 
the  third  ventricle.  The  second  vesicle  or  midbrain  forms  the  corpora  quadrigemina. 
Avhile  the  third  vesicle  divides  into  the  i.sthmus,  metencephalon,  and  mvelencephaion, 
from  which  there  are  developed  the  pons,  cerebellum,  and  medulla  oblongata. 

TJie  cerebral  portion  of  the  medullary  canal  becomes  inclosed  by  the  primitive 
vertebral  piates  of  the  head,  which  form  the  membranous  primitive  skull,  the  ba«il 
portions  of  which  become  cartilaginous  in  the  second  month  of  foetal  life.  In  the  third 
month  the  basal  cartilage  and  the  membranous  vault  begin  to  ossify. 

According  to  (t.  St.-Rihiire,  Flirster,  and  Pan  urn,  acrania  and  anencephalus  are  to 
be  referred  to  an  abnormal  accumulation  of  fluid  in  the  cerebral  vesicles,  a  hydrocepJialus. 
occurring  before  the  fourth  mouth.  Dareste  and  Perls  oppose  this  view,  and  point  out 
that  in  acrania  the  base  of  the  skull  is  usually  bulged  inward  and  not  pressed  outward, 
Th(\v  therefore  seek  the  cause  of  acrania  in  a  pressure  exerted  upon  the  cranium  from  I 
without  {Per(s),  due  to  an  abnormal  tightness  of  the  cephalic  cap  of  the  amnion,  which 
retards  the  development  of  the  cranium.  Lebedeff  seeks  the  cause  of  acrania  in  an 
abnormal!}'  sharp  bending  of  the  body  of  the  embryo,  which  he  thinks  occurs  when  the 
cephalic  end  of  the  embryo  grows  abnormally  in  the  longitudinal  axis,  or  in  case  the 
cephalic  covering  lags  behind  in  its  development. 

By  tlie  sharp  bending  the  change  of  the  medullary  groove  into  the  medullary  canal 
is  thought  to  be  liindered,  or  the  canal  after  its  formation  is  destroyed.  Fnmi  this 
could  be  explained  the  later  absence  of  the  brain,  as  well  as  of  the  membranous  and  ■[ 
osseous  cranial  covering.  The  cystic  formations  in  the  membranes  lying  upon  the 
liase  of  the  skull  are,  according  to  Lebedeff,  formed  from  the  folds  of  the  medullary 
plate,  which  sink  into  the  mesoderm  and  are  then  snared  off. 

Ihrtirig  thinks  it  possible  that  chemical  substances  circulating  in  the  blood  or 
secreted  from  the  wall  of  the  uterus  may  destroj-  the  anlage  of  the  brain. 

According  to  K.  and  ^4.  Petren,  the  spinal  ganglia  in  anencephalus  are  always  nor- 
mally developed  ;  on  the  other  hand,  the  columns  of  Clarke,  the  lateral  cerebellar  tracts, 
and  the  bundles  of  Gowers  are  either  wholly  wanting  or  are  imperfectly  developed. 
Likewise  the  pyramidal  tracts  are  wanting,  while  the  anterior-horn  ganglion-cells  and 
tile  anterior  roots  are  developed.  K.  and  A.  Petren,  therefore,  regard  the  malformation 
as  a  system-defect  in  which  the  neurones  of  the  second  order  are  not  formed  ;  and  they 
incline  to  the  view  that  the  malformation  is  to  be  referred  to  an  abnormal  anlage  of 
the  irerm. 


i 


Literature. 

(Drff'ct.s   of  i/if  Cran'nnn,    Ccrebnd  Hentia.) 
Ackermann:    Die   SehadelditTnrniitiit   be!    der   Encephalocele   cons-enita.  Ilalle-a.-S., 

IHSl. 
Arnold:  Gehirn,  IJiickenmark  ii.  Schildel  eiucs   Hemicephalus.     Beitr.  v.  Zie<rler,  xi., 

is!t2. 
Beneke;  Zwei  Fillle  von  multiplen  Ilirnhernien.     Yircli.  Arch.,  119  Bd..  1890. 
Berger;  L'origine  et  le  mode  de  developpement  de  certaines  encephaloceles.     Rev.  d^| 

ehir.,  1890.  |f 

Ernst:  Bildungsfehler  d.  Centralnervensystems  bei  Encephalocele.     Beitr.   v.  Ziegler, 

XXV..  1M99. 
Fdrster:  Missbildungen  des  Menschen.  Jena.  1865. 
Fridolin:  I'.-ber  defecte  Schildel.     Yirch.  Arch.,  116  Bd.,  1889, 
Jacoby:  Partielle  Anencephalie  bei  einem  Embryo.     Virch.  Arch.,  1-17  Bd.,  1897. 


I 


:vrALF()KMATI()\S    OF    FACE    AM)     XKCK.  f)!? 

Jonkovski:  II('iiiik('iilialio  II.  Prosoposcliisis.     Viifh.  Anii     Klil  IM     I'lO" 

Klug-e:  Hy«lrciicnkci)lialie.     Z.  f.  Heilk.,   1JHV2. 

Kundrat:  Die  Ariliineiicephalie.      Graz,  1882. 

Lebedeff:  Entsteluing  d.  Anenceplialit"  u.  Spina  bilida.     A'iicli.  Aich.,  80  IM.,  ISSl. 

Leonowa:  Aiicnoephalie.     Arch.  f.  Aiiat.,   1890. 

Manz:   Das  Aiige  liirnlostT  ]\Iissgel)urt(Mi.     Virch.  Arch.,  51  Ud.,  isTO. 

Muhr:   Knccpiialocele  anterior.     Arch.  f.  Psycli.,  viii..   1878. 

Muscatello:  Dieangch.  Spahcn  dcsSciiadels.   Langen'bcck's  Arcii..  47  IJd..  1804  (Lit.) 

Petren,  K.  ii.  G.:  Nerveusystem  bei  Aueiicephalie  u.  Amyelic.  Vircii.  Arcii     l.')!  IJd  " 

ls9S(J.it.). 
de  Ruyter:  Schildcl-  iind  Rlickgratsspalten.    Langonbeck's  Arch.,  40  Bd..  1890. 
SchiirhofF.  Anatomic  d.  Centrahicrvensystcms  bei  Ilemiccplialcn,  Stuttgart.  1894. 
Siegenheek  van    Heukelom:  Eucephalocele.     Arch.    f.    Ent\vickehi'ug.snK'cii     iv 

ISiH) 
Spring;  Monographic  de  la  hemic  du  cervcau,  Bru.velles,  18r)3. 
Ssamoylenko:  Ke]iiialocclenasofrontaiis.     Beitr    v.  Bruns,  40  Bd.,  1903. 
Sternberg  u.  Latzko.  Hemikephahis.     Z   f.  Ncrvenkrankh.,  24  B(i.,  1903. 
Talko.  Ueber  angeborene  Hirnhernien.     Vircii.  Arch.,  50  Bd.,  1870. 
Virchow.  Die  kraukh.  Geschvviilste,  i..  18G3. 


((')  The  Malformations  of  the  Faee  and  Xcrk. 

§  135.  The  developmeut  of  the  face  not  iufiequeutly  suffers  disturb- 
ances leading  to  more  or  less  marked  facial  malformations,  Avhich  may 
appear  alone  or  in  association  with  malformations  of  the  cranium.  If 
the  frontal  process  and  the  maxillary  proces.ses  of  the  hr.st  biancliial  arch 
remain  in  a  rudimentary  state  or  are  destroyed  to  a  marked  extent  by 
pathological  processes,  there  persists  at  the  site  of  the  face  an  open  sinus 
giving  ri.'^e  to  the  conditions  known  as  aprosopia  (absence  of  the  faee) 
and  schistoprosopia  (cleft  face),  which  may  also  be  associated  with  a 
defective  development  of  the  nose  and  eyes. 

More  frequent  than  these  large  defects  are  smaller  clefts  involving 
the  lips,  alveolar  process  of  the  uj^per  jaw,  the  njiper  jaw  itself,  and  the 
hard  and  soft  palates  (Fig.  386),  which  are  designated  ms  cheiIo=gna- 
thopalatoschisis  or  ♦' wolf's  jaw."  This  malformation  gives  li.sc  to  a 
communication  between  the  mouth  and  the  nasal  ca\ity  (Fig.  3SG). 
The  hard  palate  is  cleft  in  the  part  bordering  upon  the  ^•omer ;  the  soft 
palate  in  the  median  line.  In  the  alveolar  process  of  the  n])i)er  jaw  the 
clfft  runs  between  the  canine  tooth  and  the  outer  incisor  or  between  the 
outer  and  inner  incisors.  The  nmlformation  may  be  Inlaleial  or  unilat- 
eral, and  is  sometimes  ])rimary  and  inherilable,  at  other  limes  accpiired 
secondarily,  in  part  as  the  result  of  amniotic  adhesions  (  Fig.  371). 

Xot  infrequently  the  cleft  involves  only  special  ]»ortionsof  the  regions 
mentioned,  as  the  upper  lip  (harelip,  lahiuni  Irporiiixm),  or,  what  is 
rarer,  only  the  hard  or  soft  palate.  The  lightest  grades  of  this  form  of 
cleft-malformation  are  represented  by  a  notch  or  cieatriciid  tine  in  the  lips, 
or  l»y  a  hifiireatioii  tftlie  nrula. 

Prosoposchisis  or  oblique  facial  cleft  (Fig.  372;  is  the  designation 
ap])lied  to  a  cleft  running  obliquely  from  the  month  to  an  oibit.  It  is 
usually  a.ssociated  with  malformations  of  the  brain.  Aecoiding  to 
Moriau,  three  forms  may  be  distinguished.  The  lir.st  is  a  cleft  beginning 
in  the  upper  lip  as  a  harelip,  passing  into  the  nasal  cavity,  thence 
ai((und  the  ala  nasi  toward  the  orbit,  and  may  extend  even  beyond  the 
latter.  The  second  form  likewise  begins  in  the  region  of  a  Ijarelip,  but 
extends  outward  from  the  nose  toward  the  orbit.  The  third  form  ex- 
tends from  the  corner  of  the  mouth,  outward  througdi  tlie  cheek  toward 
the  canthus  of  the  eye,  and  divides  the  superior  maxillary  process  exter- 


51S 


DISTl'RBAXCES    OF    DEVELOPMENT. 


ually  ro  the  canine  tooth.  A  transverse  cleft  of  the  cheek  also  occurs,  pass- 
ing;- from  tlie  corner  of  the  mouth  toward  the  temporal  region. 

riedian  facial  clefts  (nasal  cleft)  run  in  the  median  line  involving 
the  nose,  upper  jaw,  and  also  the  lower  jaw,  and  may  extend  as  far 
down  as  the  sternum.  The  tongue  may  also  he  cleft.  Further,  the  de- 
fect may  extend  even  to  the  frontal  bone  and  brain. 

All  of  the  above-mentioned  clefts  may  be  confined  to  small  x)ortioiis 
of  the  regions  mentioned,  and  moreover  attain  varying  depths. 

If  the  development  of  the  inferior  maxillary  iDrocess  of  the  first 
brancliial  arch  is  retarded,  the  inferior  maxilla  also  is  imperfectly  devel- 
oped or  wholly  wanting,  and  there  arise  those  malformations  known  as 
brachygnathia  or  agnathia  (Fig.   387).     The  lower  portion  of  the  face 


Fig.  386.-Double  olici 

(Wolf: 


o-crnatliopalatoschisis. 
jaw.) 


— Aarnathia  and  svnotia. 
(After  Guardan.) 


appears  as  if  cut  away;  the  ears  are  sometimes  brought  so  close  to  each 
otlier  as  to  touch  (si/notia).  Usually  the  superior  maxillary  processesi 
are  also  imperfectly  developed ;  not  infrequently  the  ear  is  malformed, 

Abnorural  largeness  of  the  mouth  (macrostomia),  abnormal  smallness 
(microstomia),  closure  (atresia  oris),  and  duplication  of  the  mouth  (dis- 
tomia)  are  all  rare. 

Wlien  the  embryonic  external  branchial  clefts  or  internal  branchial 
l)ockets  fail  in  part  to  close,  there  persist  fistulse  opening  either  exter- 
nally or  internally,  or  closed  cysts.  The  former  condition  is  known  as 
fistula  colli  congenita.  The  mouths  of  the  external  fistuLT  are  usuallyl 
found  at  the  side  of  tlu>.  neck,  more  rarely  nearer  to  the  median  line  or 
in  the  median  line;  those  of  the  internal  fistultie  open  into  the  pharynx, 
trachea,  or  larynx.  Very  often  the  remains  of  the  branchial  pockets 
form  only  diverticula  of  the  last-named  organs.  The  fistula?  are  for  thel 
chief  ])art  covered  with  mucous  epithelium,  sometimes  ciliated,  arising 
therefore  from  the  visceral  branchial  pockets,  according  to  von  Kos 
tanecki  and  von  Mielecki  usually  from  the  second.  In  rare  cases  there 
is  found  a  complete  branchial  fistula  with  both  external  and  internal 
oix'uings. 


malfor:\iattoxs  of  face  and  neck.  519 

The  branchial  cysts  arisin<j^  fioin  tlic  branoliial  ])orkets  are  sonic- 
tinies  lined  uilli  mueous  epithelium  (eilialed  ei)itlieliiiiii)  and  contain 
fluid;  hence  they  are  called  lii/tlrocrh'  colli  anujcuHd.  At  other  tiin«'s  they 
possess  an  epideiiuoidal  covering- and  inclose  eiiidennoidal  coli-inasscs, 
and  are  therefore  classed  uitli  the  (ithn-o)ti(i(<i  \\m\  dcniioid  ci/.sfs.  Cysts 
of  the  neck  lying-  in  the  median  line  and  reaching-  to  the  liyoid  bone  nia\- 
develop  from  remains  of  the  ductus  thyreoi;lossns. 

The  face  and  neck  are  developed  in  part  from  a  single  anlage,  and  in  part  from 
paired  anlage.  Tlie  latter  are  represented  iu  the  branchial  or  visceral  arches  growing 
from  the  lateral  portions  of  the  base  of  the  skull  veiitrally  in  tlic  primitive  throat  wall. 
The  single  anlage,  designated  the  frontal  ])roeess,  is  a  pmlongaiion  downward  of  tlic 
base  and  vault  of  the  cranium,  and  is,  in  fact,  nothing  more  tluui  the  anterior  end  of 
the  skull.  Between  the  individual  branchial  arches  there  are  at  a  certain  period  clcfl- 
like  depressions  known  as  the  branchial  pockets. 

The  frontal  process  and  tlie  tirst  branchial  arch  form  the  bovuularies  of  the  great 
primitive  mouth-opening,  which  lias  a  diamond  shape.  In  the  course  of  development 
the  tirst  branchial  arch  sends  out  two  processes,  the  shorter  of  which  applies  itself  to 
the  under  sin-face  of  the  anterior  portion  of  the  liead  and  forms  the  upper  jaw,  wiiilc 
from  tlie  longer  one  the  lower  jaw  is  developed.  The  frontal  process,  which  forms  the 
anterior  boundary,  gives  rise  to  a  broad  prolongation  of  the  forehead,  and  then  pushes 
on  two  lateral  processes  which  are  known  as  the  lalcial  nasal  processes.  By  fnrther 
differentiation  of  the  central  portion  of  the  frontal  pkk  rss  jUMpir,  the  septum  narium 
is  formed,  which  by  means  of  two  spurs,  the  inner  nasal  priKcssis,  i)roduces  the  borders 
of  the  external  nasal  opening  and  the  nasal  furrow.  The  lateral  nasal  processes  are  the 
lateral  portions  of  the  skull,  and  later  develop  within  themselves  the  ethmoid  labyrinth, 
the  cartilaginous  roof,  and  the  sides  of  the  anterior  portion  of  the  nares.  At  a  certain 
stage  they  form  with  the  superior  maxillary  process  a  furrow  running  from  the  nasal 
furrow  to  the  eye,  the  lachrymal  fissure. 

In  the  beginning  the  mouth  is  simply  a  large  sinus,  but  is  soon  separated  into  a 
lower  and  larger  digestive  and  an  upper  and  smaller  respiratory  portion.  This  separa- 
tion is  brought  about  by  the  development,  from  the  superior  maxillary  processes  of  the 
first  branchial  arch,  of  the  palatal  plates,  which  from  the  eighth  week  on  blend  into 
each  other  and  at  the  same  time  unite  witli  the  lower  border  of  the  nasal  septum.  The 
union  of  the  anterior  portions  of  the  palatal  plates  takes  place  earlier  than  that  of  the 
posterior  portions. 

Through  the  union  of  the  contiguous  portions  of  the  frontal  and  nasal  processes 
wL':j  the  superior  maxillary  jirocesses  the  cheek  is  formed  and  a  continuous  superior 
maxillary  border,  from  whicli  are  developed  later  the  lip  and  the  alveolar  process  of 
the  upper  jaw  and  intermaxillary  bones,  wliile  the  external  jiortion  of  the  nose  devel- 
ops from  the  frontal  process.  The  intermaxillary  bones  are  developed  as  independent 
bones,  but  unite  very  early  with  each  other  and  with  the  ujiper  jaw. 

Literature. 

(Wolfs  Jaw;  HareUp ;  Oblique  Facial    Clefts.) 

Albrecht.  Arch.  f.  Chir.,  xxxi. ;  Fortschr.  d.  Med.,  iii  ,  1885:  Biol.  Chi.,  v  ,  18S6. 

Battels ;  Ueber  vernarbte  Lippensi)alten.     Arch.  f.  Anat.  u    Pliys.,  1872. 

Biondi:  Lippenspalle  uiul  deren  Coiiiplicationen.     Virch.  Aicli.,  Ill  Hd.,  1888. 

Forster:   Die  INIissbildunger  des  ]\Ieiisclien,  Jena,  18()o. 

Hayniann:  Amniogene  erixiche  llasensciiarten.     l.-l).,  Leipzig,  lfl08. 

Kindler    Linksseit.  Nasenspalte  verbunden  mit  Defect  d.  Stirnbeins.     Beitr.  v.  Ziegler, 

vi  .  1880. 
Kolliker,  Th. :  Ueber  das  Os  intermaxillare  u.  d.  Anatomic  d.  Ilasenscharte  u    d. 

Wolfsiachens,  Halle,  1882;  Die  einfache  Anlage  des  Zvvi.schcnkiefers.     Anat.  An/., 

iii..  1890. 
V.  Kostanecki:  Missbildungen  in  der  Kopf-  u.  Ilalsgegend.     Virch.  Arch.,  ICi  Bii  , 

IS'.ll. 

Kredel;  Angeb.  Nasenspalten.     Dent.  Zeitschr.  f.  Chir.,  4"^  Bd.,  1898  (Lit.). 
Lannelongue  :  Du  developpement   de   rintermaxillaire   externe   et   de   son  incisive; 

pathogenic  des  fissures  osseuses  de  la  face.     Arch,  de  med.  cxp.,  ii.,  1890. 
Lexer:  Angeb.  mediane  SpaUuiig  der  Nase.     Arch.  f.  klin.  Chir.,  G'iBd..   1900. 


520  DISTX  RBAXCES    OF    DEVELOPMENT. 

Madelung-:    Untoilippoufistel   u.    seitl.    Nasenspafte.     Langenbeck's  Arch.,   37   Bd., 

ISS'J. 

Marwedel:  i\Ic(liaiic3  Spalte  der  oberen  Gesichtslmlfte.     Virch.  Arch.,  163  Bd.,  1901. 

Merkel;  (Jcsichtsspaltc.     Topograph.  Anatomic,  ii.  Heft,  1887. 

Morian:   Die  schrai^c  Gcsichtsspalte.     Arch.  f.  Chir.,  xxxv.,  1887. 

Mliller:  Die  llascn,scliartcn  d.  Tlibinger  chir.  Kliuik  i.  d.  J.,  1843-85,  Tubingen,  1885, 

Nasse:  :Mcdianc  Nasenspalte.     Langenbeck's  Arch.,  49  Bd.,  1895. 

Schmidt:  Spaltbildung  im  Bereiche  d.  mittl.  Stirnfortsatzes.     Virch.  Arch.,  16-2  Bd., 

1!)(K). 
Stohr:  Ziir  Zwischeukieferfrage.     Arcli.  f.  kiin.  Chir.,  xxxi.,  1885. 
Taruffi:  ("asi  di  meso-riuo-schisi.     Mem.  deihi  li.  Ace.  delle  Sc.  dell'  Istii.  di  Bologna, 

ISilO. 
Warynski;  Bee  de  lievre  simple  ct  complexe.     Virch.  Arch.,  112  Bd.,  1888. 
Wdlfler:  Zur  Casuistik  der  medianeu  Gcsichtsspalte.     Langenbeck's  Arch.,  40  Ba., 

1S90. 
Wolff:  Ilasenscharte.     Eulenburg's  Realencyklop.,  1896  (Lit.). 

(Bra)ichial -cleft  Fistulw  and  Cysts,) 

Baumgarten  n.  Neumann:  Fistula  colli  congenita.     Arch.  f.  klin.  Chir.,  xx.,  1870. 
Bidder:  Knorpcliicsrhwulst  am  liaise.     Virch.  Arch.,  120  Bd.,  1890. 
Franks;  Blulcvsten  d.  seitl.  llalsgegend.     Deut.  Zeitschr.  f.  Chir..  28  Bd.,  1888  (Lit.). 
Frobenius :  Leber  einige  angeb.  Cystengeschwulste  des  Halses.     Beitr.  v.  Ziegler,  vi., 

1SS9. 
Hammar:  Kongen.  Halskiemenfistel.     Beitr.  v.  Ziegler,  xxxvi.,  1904. 
Heusing-er .  Virch.  Arch.,  29  and  33  Bd. ;  Deut.  Zeitschr.  f.  Thiermed.,  ii.,  1875, 
Konig-;  Fistula  colli  congenita.     Langeiil)eck\s  Arch.,  51  Bd.,  1896. 
V.  Kostanecki;  Zur  Kenntn.  d.  riiarynxdivertikel  des  ]Meuschen.     Virch.  Arch.,  IIV 

l!(l.,  INS!). 
V.  Kostanecki  u.  v.  Mielecki;  Die  angeb.  Ilalskiemenlisteln.     Virch.  Arch.,  120  u. 

121  Bd.,  1890. 
Nieny:  JIalskiementisteln.     Beitr.  v.  Bruus,  23  Bd.,  1899. 
Richard:  Geschwiilste  der  Kiemenspalteu.     Beitr.  v.  Bruus,  iii.,  1888  (Lit.). 
Schlange;  Fistula  colli  congenita.     Langenbeck's  Arch.,  46  Bd.,  1893. 
Schmidt:  Ilalskiementisteln  beim  Kalbc.     Zeitschr.  f.  Thiermed.,  i.,  1897. 
Striibing-:  Zur  Lehre  v.  d.  congen.  Hals-Luftrohrentisteln.     Deut.  med.  Woch.,  1892. 
Virchow:  Halskiemenfistel.     Virch.  Arch.,  32  Ikl.  ;  Tiefes  auriculares  Dermoid.     lb., 

;ilBd  ,  1866. 
Zahn:  Kiemengangsfisteln.     Zeitschr.  f.  Chir.,  xxii.,  1885. 

((/)  FauUy  Closure  of  the  Abdominal  and  Thoracic  Cavities,  and  the  Accom- 
panijing  ^falforinations. 

§  I'M).  Arrests  of  development  in  the  formation  of  the  ventral 
body=wall  may  take  place  at  different  points  and  exhibit  different  orade.s 
of  sevei-ity.  They  occiTr  most  frequently  in  the  region  of  the  tunbilicus, 
where  the  closure  of  the  abdominal  cavity  takes  place  latest.  In  the 
case  of  imperfect  development  of  the  abdominal  wall  at  this  point,  so 
that  a  more  or  less  extensive  area  of  the  abdominal  cavity  is  closed  in 
only  by  the  peritoneum  and  the  sheath  of  the  umbilical  cord— that  is, 
the  amnion— wliich  are  ])ushed  forward  by  the  abdominal  organs  (Fig. 
:).S.S),  tlu'ic  is  produced  tiie  condition  known  as  omphalocele,  or  hernia 
funiculi  umbilicalis,  or  umbilical  hernia.  The  umbilical  cord  is  at-, 
tached  either  to  the  summit  or  at  one  side  of  the  hernial  sac,  and  is  more\ 
or  less  shortened. 

If  the  anterior  abdominal  walls  either  wholly  or  in  part  fail  to  unite, 
there  arise  those  conditions  w^hich  are  designated  fissura  abdominalis, 
or  gastroschisis  completa  and  thoracogastroschisis.  These  are  char- 
acterized by  llie  undevelo]ied  abdominal  coverings  not  having  been  sepa- 
rated from  the  amnion,  l)ut  ])assing  into  it.  The  gi'eater  part  of  the 
abdominal  organs  lies  in  a  sac  formed  by  the  amnion  and  peritoneum 


MALFORMATIONS    OF    TllOKAX    AXD    AliDO.ME.V. 


o2l 


(evoitmtion).  The  peritoneuin,  however,  may  also  be  wautiiijj;,  likewise 
the  umbilical  cord,  and  the  umbilical  vessels  may  pursue  their  coui-se  to 
the  placenta  independently. 

A  cleft  contined  to  the  thorax  is  called  thoracoschisis.  Should  liu' 
heart,  covered  only  with  pericardium  or  wholly  lice,  pidtrudc  Ihidu-h 
an  openiug  iu  the  cardiac  region,  the  coudition  is  dcsiiiiiatcd  ectopia 
cordis. 

When  the  failure  to  close  is  coulined  lo  the  ivgiou  of  the  sternum, 
the  condition  is  designated  fissura  sterni.  This  defect  may  involve 
either  the  whole  or  a  part  of  the  sternum,  at  times  atfecliug  tiie  Ixmes, 
al  other  times  only  the  skin. 

The  protrusion  of  the  urinary  bladder  through  a  clelt  in  the  abdomi- 
nal wall  is  known  as  ectopia  vesicas  urinariae. 

Clefts  of  the  abdominal  wall  are  not  infre({uently  associated  \\ilh 
clefts  of  the  parts  lying  behind  the  wall,  not  only  in  the  case  of  large 
clefts  (total),  but  also  in  the  case  of  smaller  ones  (partial).  When  a 
cleft  of  the  lower  portion  of  the  abdominal  M'all  is  associated  with  a 
cleft  of  the  urinary  bladder,  so  that  the  posterior  wall  of  the  latter  i)ro- 
trudes  through  the  abdominal  fissure  (Fig.  389,  c),  the  condition  is 
known  as  fissura,  or  exstrophia,  or  inversio 
vesicas  urinaria^.  Occasionally  the  pelvic 
<;iidle  and  the  uiethra  are  also  cleft,  the  latt<M- 
beinu  i(  piesented  by  a  groove  ojxmi  anterioily 
(Fig  380,0.  The  exstrophy  is  then  sai«l  to 
be  complicated  b\  a  fissura  genitalis  and  epis- 
padias. 

A\  hen  an  abdominal  fissure  or  an  abdominal 
and  \esical  fissuie  is  combined  with  a  lissure 
ot   the  intestines,  there  is  produced  a  fissura 
abdominalis  intestinalis  or  vesicointestinalis. 
The  intestinal   hssnic  is  sit- 
uated in  the  ca'cum  or  be 
ginning   of   the    colon,    and 
the    mucous    membi-ane    of 
the  cleft  intestine  i)rotrudes 
through  the  opening  in  the 
p  "^-^^       "    ^     /"'i  ^  '*^  I /^  f     \  samemaiinei-astlu^  jiosterior 

■       ^^  -'        '  ^    ?^      -f  ^^..jjl  ,,f-  ,,„.  i,ia,Uler,  so  that 

the  condition  is  called  ex- 
strophia or  inversio  intes- 
tini. 

If  the  omphalomesenteric^ 
duct  does  not  undergo  its 
normal  involution,  there  i<'- 
mains  at  the  lower  end  of 
tlui  small  intestine  an  ap- 
])endix  of  intestine  called 
Meckel's  diverticulum. 
which  arises  ))eri)endicularly 
from  tile  outer  margin  of  tlie 
intestine.  It  has  usually  the  appearance  of  a  glove-linger,  and  is  eitiier 
free  at  its  end  or  attached  to  the?  umbilical  ring,  sometimes  being  dilated 
at  its  end.  In  the  case  of  adhesion  to  the  umbilical  ring  the  intestinal 
mucosa  may  appear  at  the  navel  in  the  form  of  a  tumor  {ectopia  inirntini, 


522 


DISTtRBAXCES  OF  DEVELOPMENT. 


adenoma  mnhUlealf).     In  very  rare  cases  a  cyst  lined  with  mucous  mem- 
brane may  be  formed  in  the  abdominal  wall  {omphaJomesenteric  cyst). 

Congenital  fistulte  of  the  urachus,  that  is,  fistula)  lying  within  the  um- 
bilicus and  connecting  with  the  bladder  by  a  fistulous  tract,  depend  upon 
an  incomi)lete  obliteration  of  "he  urachus  or  of  the  stalk  of  the  allautois. 
They  may  be  associated  either  with  an  open  or  a  closed  urethra. 


Fig.  389.— Fissura  abdoiuiuis  et  vesica?  urinariie  in  a  Rirl  eig-htpen  days  old. 
Jj,  peritoneum ;  c,  bladder ;  d,  small  bladder-cavity  corresponding  to  tlie  trigonum  : 
J,  labia  minora. 


I.  Border  of  the  skin ; 
trough-like  urethra; 


The  development  of  the  body-form  from  the  flat  embryonic  anlage  begins  by  a 
snaring-o£f  of  the  individual  germ-layers  from  the  outer  embryonal  area,  and  their  fold- 
ing to  form  two  tubes,  tiie  body-wall  and  the  alimentary  canal. 

The  infolding  of  these  layers  takes  place  at  the  cephalic  and  caiidal  ends,  as  well  as 
at  the  lateral  portions  of  the  embryonal  anlage,  and  as  the  summits  of  the  folds  gradu- 
ally grow  together  from  all  directions,  those  which  form  the  body-wall  produce  a  tube 
whose  cavity  finally  communicates  only  at  tiie  parietal  umbilicus,  by  means  of  a 
peduncle-like  prolongation,  with  the  cavity  of  the  extra-embryonic  portion  of  the 
blastoderm  known  at  this  time  as  the  vitelline  membrane.  While  the  lateral  and  ven- 
tral walls  of  tiie  embryo  are  being  thus  formed,  within  the  body  the  intestinal  furrow 
also  closes  to  form  a  tube,  which  is  in  communication  at  only  one  point  lying  within 
tlie  parietal  imibilieus,  known  as  the  visceral  umbilicus,  with  "the  cavity  of  the  umbili- 
cal vesicle,  by  means  of  a  channel  known  as  the  omphalomesenteric  duct. 

Umbilical  hernia  and  clefts  of  the  upper  portion  of  the  abdominal  wall  are  fre- 
quently combined  \;itli  craniorachischisis,  while  exstrophy  of  the  bladder  and  intestine 
is  often  associated  with  myelocystocele.  According  to  von  Beckling/imisen,  the  two 
malformations  are  to  be  regarded  as  coordinated  with  each  other.  Further,  large  ab- 
dominal clefts  are  often  associated  with  lordotic  and  scoliotic  ciuwatures  of  the  spinal 
column. 

Literature. 

{Clcfis  of  Tlioraclc  and  Abdominal  Walls ;  Mecl-cVs  Diverticulum  ;  Ectopia 

Tiitestini.) 

Aschoff:  Vcrhilltniss  d.    Leber   u.   d.    Zwerchfells    z.    Nabelschnurbrlichen.     Virch. 

Aich..  144  Rd  ,  189(5  (Lit.). 
Chaudelux:  01)servation  potir  servir  a   Thistoire  de  Texomphale.     Arch.    d.    phys., 

viii.,  1881. 
Herzog:  Die  Riickbildung  des  Nabels  u.  der  Xabelgefasse,  Miinchen,  1892, 
Jahn:  Lfachustisteln.     Beitr.  v.  Bruns.  2(5  Bd.,  1900  (Lit.). 
Klautsch:  Bauchspalten.     Cbl.  allg.  Path.,  vi.,  1895. 


MALFORMATIONS    OF   EXTERNAL    GENITALL\. 


523 


^t  am  Nabel.     Arc!,    f.  Gyn. 


Etistner:  Das  Adonom  mid  die  Gramdaliorisgcsi 

ix.,  1877;  Virch.  Arch.,  G9  IM..  1S77. 
Preisz;  Ul'Ij.  d.  soi^-.  Nalu'ladciioin.     Jalirb.  f.  Kiiulcrlicilk.,  ,13  Bd.,  1891. 
V.  Reckling-hausen :  Spina  bifida.     Vircii.  Arch.,  105  IJd.,  lS8(i. 

Rischpler :  i)rci  Falle  von  Eventration.     Arcli.  f.  Knt\vickeinns,<,nnecli.,  vi.,  1898  (Lit.). 
Saner:  Prt)laps  ciues  olTcueu  Meckel'schca  Divertikeis.     Deiit.   Zeitsclir.   f.  Chir.,  44: 

Vh\.,  1897. 
Schild:  Congeu.  Ektopie  der  ILarnblase.     Arb.  a.  d.  path.  Institute  in  Milnchen.  1886. 
Siegenbeek  van  Heukelom:  Die  Geuese  der  Ektopia  vcntrieuii  am  Nabcl.     Yiich. 

Anil.,  Ill  JM.,  1888. 
Tillmanus:  Aniicl).  Prolaps  der  Magenschleimhaiit  durcii  den  Nabelring   und  ul)er 

sonstiuc  Gcs(  hwulsle  nnd  PMsteln  des  Nabels.     Deut.  Zeitschr.  f.  Cinr.,  xviii.,  1883. 
Vejas:   i'/m.'  sclicnc  Missbiklnng.     Virch.  Arch.,  104  Bd.,  1880. 
Zumwinkel:  SulKUtaiic  Dottergangscyste.     Langcnbeck's  Arcli.,  40  Bd.,  1890. 


[(')  Mdl/oniKitioiis  of  the  External  Genildlia  <ni(I  ^Ihk.s,   due  to  Arrested 
DereJopinent. 

§  137.  Malformations  of  varying  degree  of  the  external  genitals  may 
be  associated  with  malformations  of  tiie  abdominal  wall,  bladder,  and 
the  internal  genital  organs,  or  may  occnr  independently  of  these.  Com- 
plete absence  of  the  external  genitalia  occurs  most  frequently  in  con- 
nect ion  witli  other  malformations  of  this  region,  particularly  in  the  case 
of  sirenomelia,  yet  the  region  may  in  general  present  also  a  normal 
structure  (Fig.  392).     The  internal  genitals  are  usually  also  malformed. 

A  stunted  condition  of  the  penis  is  not  rare,  tlie  organ  in  conse- 
quence coming  to  resemble  moi(;  or  less  tlie  clitoris.  This  condition  is 
usually  associated  with  a  hypospadias^that  is,  the  urethra  opens  on 
the  under  side  of  the  organ,  either  beneath  the  glans,  the  body  or  the 
root  of  the  penis  (Fig.  390),  or  finally  even  behind  the  scrotum  {hijpo- 


-Hypospadias  with  stuntiiif,'  of  Hk;  pcni: 
Reduced  one-fourtb. 


Fio.  391.— EpI.spadta 
(After  Ahlfeld.) 


spadias  jyenneonerotaUs).  These  malformations  may  exist  in  jx-nisrs 
otherwi.se  normally  develoi^ed,  and  depend  upon  a  ])arlial  failure  (d"  the 
sexual  fuii-ow  to  close. 

Epispadias  (Fig.  391)  is  that  condition  in  which  the  nrdhral  o])eiiiiig 
is  found  upon  the  dorsum  of  the  penis.  It  is  more  lare  than  hyi)o- 
spadias,  and  is  dependent  upon  a  defective  or  delayed  closnre  of  the 
pelvis,  so  that  tlie  cloaca,  before  the  closure,  becomes  divided  into  an 
intestinal  (anal)  and  a  genital  opening  (Thierscli).     Under  certain  con- 


624 


DISTURBANCES    OF    DEVEL0P:MENT. 


ditions  the  penis  remains  cleft  throughout  its  entire  length ;  at  the  same 
time  a  tissuie  of  the  bladder  and  abdomen  may  be  present. 

Hypertrophy  of  the  prepuce  is  not  rare.     If  the  preputial  opening 
is  narrowed  so  tliat  Uu-  ]»i('piic(' cannot  be  drawn  back  over  the  glans, 
the  condition  is  desi.iiiiatcd  a  hypertro= 
phic  phimosis.     Total  absence  of   the 
prepuce  is  rare ;  an  abnormal  shortness 
is  nioic  frcciuent. 

Defective  development  of  the  scro- 
tum is  usually  associated  with  retention 
of  the  testicles  in  the  abdominal  cav- 
ity or  in  the  inguinal  canal,  and  leads 
to  appearances  whereby  the  external 
genital  organs  of  the  male  come  to  re- 
semble those  of  the  feniiile,  especially  so 
when  tlie  penis  is  also  stunted. 

In  the  female  the  clitoris  as  well  as 
the  labia  majora  and  minora  may  show 
a  stunted  development.  Epispadias 
and  hypospadias  occur  also  in  the  fe- 
male sex,  the  former  coincidently  with 
a  fissure  of  the  abdominal  and  bladder 
walls  (Fig.  389).  In  hypospadias  a 
portion  of  the  posterior  wall  of  the  ure- 
thra is  lacking,  and  the  urethral  open- 
ing may  be  found  at  a  greater  or  less 
distance  within  the  vagina. 

Absence  of  the  urethra  occurs  in 
both  sexes  (Fig.  302).  In  girls  the 
bladder  may  open  directly  into  the 
vagina. 

Closure    (atresia)    of  the   urethra 
occurs  likewise  in  both  sexes,  and  re- 
sults either  from  a  partial  defect  of  the  same  or  from  obliteration  of 
the  orifice.     An  accumulation  of  urine  in  the  bladder  may  lead  to  a 
marked  dilatation  of  the  same  (Fig.  392). 

An  abnomal  narrowness  of  the  urethra  may  exist  in  a  portion  of 
its  course  or  thronghout  its  entire  length.  Further,  its  lumen  may  be 
narrowed  as  the  result  of  a  hypertrophic  development  of  the  colliculus 
seminalis. 

In  rare  cases  multiple  orifices  of  the  urethra  have  been  observed. 
Fuither,  in  men  there  maybe  found  in  the  glans  penis  a  blind  tube 
lying  iK'side  llie  urethra. 

Atresia  ani  simplex  is  a  closure  of  the  anus,  the  intestine  being  at 
the  sanies  time  well  developed.  It  may  arise  from  a  failure  of  the  ecto- 
derm to  i'old  in  at  the  anal  site,  oi- a  cloaca  already  existing  and  open- 
ing outward  may  again  become  closed  through  subsecpient  adhesions 
<  l-'rank  ).  If  the  j'ectum  does  not  end  immediately  above  the  anal  mem- 
biaiie  butr  liigher  up,  tliere  exists  in  addition  to  the  atresia  ani  also  an 
atresia  recti,  a  malformation  which  may  occur  even  when  the  anus  is 
well  developed. 

When,  with  absence  of  the  anus,  there  is  also  an  arrested  development 
of  the  vaginal  wall,  which  grows  downward,  between  the  sinus  urogeni- 
talis  and  intestine,  to  unite  with  the  perineum,  there  remains  a  cloaca 


Fig.  392.— Complete  absence  of  the  urethra 
and  external  genitals,  with  extreme  dis- 
tention of  the  body  due  to  an  enormous  <hl- 
atation  of  the  bladder.  Compression  and 
stunting  of  the  lower  extremities.  (In  tht- 
posterior  wall  of  the  bladder  nidiments  of 
a  female  genital  apparatus  in  the  form  of 
portions  of  the  tubes  and  ovaries  wir.- 
found.) 


MALFORMATIONS    OF    THE    P.XTliE.MITIKS,  525 

in  which  the  sinus  uri><ieuitalis  and  llic  end  <»r  llic  howt-l  unite.  In 
otlier  cases  there  are  found  fistulous  communications  between  the 
rectum  and  tlie  bladder  oi-  urethra  (  in  boyst  on  the  one  Jiand,  or  Ik- 
tween  tlie  rectum   and  tlie  vagina  or  uterus  on  tiie  other  (atrrsia  oui 

vcsicdlis,  urctltnilis,  r(((/iiia/is,  iilcriixi  ). 

In  rare  eases  the  intestine,  in  tiie  ease  of  anal  atresia,  may  open 
outward  l»y  means  of  external  fistula;  in  the  ])erineum,  serolnni,  or 
sacrum.  Further,  external  fistuhTJ  behiw  the  anus  may  occur  as  remains 
of  the  post-anal  gut. 

Literature. 
(J)i.sti(rba)i<y's  of  Devrlopmod  of  ilie  External  (imiUdiK  and  of  the  Anus.) 

Bertholdy:  Fistula  aai  cougenita.     A.  f.  Ivlin.  Ciiir.,  6G  JJd.  190-3. 

Bergh:  Epispadie.     Vlrch.  Arch.,  61  Bd..  18C7. 

Dienst:  Atresia  ani  cougenita.     Yirch.  Arch.,  1.j4  Ikl.,  1898  (Lit.). 

Eppinger:  Atresia  ani.     Prag.  med.  Wocli.,  1880. 

Frank:   Die  angeborene  Verschliessung  des  Mastdarnis,  Wien,  1892. 

Fiirst:  Weililiclie   Epispadie   mit   Xaijcl-Urachustistei.     Arch.    f.    Kiudcrlicili^.,  xiv., 

lSiC,\ 
Gartner:  Atresie  des  Darms.     Jahrb.  f.  Kinderhcilk.,  .\x.,  1883. 
Goldmann:  Hypospadie.     Beitr.  v.  Bruns,  xii.,  1894  (Lit.). 

Keibel:  Entwickelung  v.  Harnblase,  Harnrohre  u.  Danim.     Verii.  d.  Anat.  Ges.,  189.1. 
Loewy:  Cong.  Dilatation  d.  Harnblase.     Prag.  med.  AVoch.,  1893. 
Mayr:  Klnakenbildung  ])ei  Hausthieren.     Ergebu.  d.  allg.  Path.,  iv.,  1899. 
Rasch:   Wcililiche  Epispadie  u.  Fissnra  vesica}.     Beitr.  v.  Bruns,  xviii.,  1897. 
Reichel:  Entstehung  d.  Missbild.   v.   Harnblase  u.   Harnrohre.     Langenb.   Arch.,  40 

B(l.,  is;):i 
Roth:  ^lissbilduugen  ini   Bereiche   des  Ductus  omphaloniesentericus.     Yircii.  Arcli., 

86  lid.,  1881. 
Soberer:  Imperforation  des  Anus.     Arch.  f.  Kinderheilk.,  xiv.,  189'2. 
Schneider:  Atresia  ani  uterina  et  vesicalis.     Arb.  her.  v.  Baiuiigarten,  i.,  1892. 
Schwyzer:  Atresie  der  Harnrohre.     Arch.  f.  Gyu.,  43  Bd.,  1892. 
Seidler:  Anus  vaginalis.     Arb.  a.  d.  pathol.  Inst,  zu  Gottingen,  Berlin,  1893. 
Stieda:  Atresia  ani  congenita.     A.  f.  Klin.  Chir.,  70  Bd.,  1903. 
Thiersch:  Entstehung  u.  Bchandlung  d.  Episi)adi('.     Arch,  d,  Ileilk.,  x.,  1869. 

(/  )  Malformations  of  the  ExtremUlen  due  to  ^ir  rested  l>er<h>j)nienf. 

§  138.  Defective  development  of  the  extremities  is  not  la.c,  and  is 
to  be  referred  in  part  to  a  primary  defect  of  the  anlaj;(*  of  an  extremity, 
in  part  to  a  disturbance  iu  the  later  develojunent  of  tlie  liml)sor1he 
hones,  and  in  part  to  constrictions  caus<'d  l)y  strands  of  the  IVetal  mem- 
luaues  or  l)y loops  of  the  nmbilieal  eoid.  Further,  such  defective  devel- 
o])ment  of  the  extremities  may  also  follow  malformations  of  the  <'entral 
nervous  system.  According  to  the  degree  and  the  kind  (tf  malformation, 
liie  following  different  forms  may  be  distinguislunl: 

(1)  Ameliis.  The  extremities  aie  eompletely  al)sent ;  in  their  i)lace 
a ic  found  only  Martv  or  stumpdike  ludiments.  The  trunk  is  usually 
w  ell  formed  (  Fig.  393). 

(2 )  Peromelm.     Stunting  of  all  the  extremit  ies. 

(3)  Phoeomeliis.  The  hands  and  feet  are  alone  dextdoped  and  are 
attached  directly  to  the  sh(»nldei-  and  ])elvis  resi)ectively. 

(4)  Mlero'^nehts  ( nilcrobraehlns,  mlcropus).  The  ext  ivmit  ies  are  <level- 
oped,  but  are  abnornutlly  small  (Fig.   394). 

(5)  Ahrachlu.s  imd  Apn.s.  Absence  of  ui)i.er  exlivniil  ies  with  well- 
de\eloped  lower  ones,  or  vice  versa. 

(6)  Perohrachius  und  Ferojms.  Stunting  of  the  ii|.p«-i'  «'i-  l"\ver  ex- 
tremities. 

(7)  Monohraclilus  or  ^fonop1lx.  Absence  .d'  one  .d'  tii<-  npper  or 
lower  extremities. 


526 


DISTURBANCES  OF  DEVELOPMENT. 


(8)  Synqyus,  SirenomeUa,  Symmelia.  The  lower  extremities  are  fused 
togetlier  (Figs.  305,  396),  and  at  the  same  tiuie  turned  upon  their  axes 
so  that  their  external  aspects  are  in  contact.      The  pelvis  is  usually 


Fig.  393.— Amelus. 


Fig.  394.— Micromelus  with  cretin-like  fades. 


Fig,  895.-Sympus  apus. 


Fig.  39G.— Sympus  dipus. 


MALFOR-MATIOXS    OF    THE    EXTKK.MITIK 


527 


defective,  as  are  also  the  external  fieiiitalia,  the  Machlci,  met  In  a,  and 
the  amis.     At  the  end  of  the  blended  extreniilios  iVct  nia\  1k'  cntiivly 


Fig.  397.— Absence  of  femur  and  fibula.    Diminution  In  the  number  of  phalanges.    One-half  natural  size. 
Fifi.  398.— Perodactylism  with  syndactylism.    Left  hand  of  a  new-born  child.    Seven-eifrhths  natural  size. 
Fig.  399.— Skiagraph  of  same  hand  as  in  Fig.  398.    Seven-eighths  natural  size. 


■vrauting  (s}/m2)us  apus)  and  only  a  few  toes  may  be  ])res(Mit  ( Fi,!?.  39.~>); 
in  other  cases  (Fig.  39G)  one  (si/)>q)u>i  vionopiis)  or  l)oth  feet  may  be  pres- 
ent (synqrus  dijJus). 


Fig  400. 


Fig.  iOO.— Malformation  of  the  right  hand,  perochinis,  with  blending  of  tlie  Ilngi-rs.  (After  Otto.)  a. 
Supernumerary  thumb;  h,  thumb  proper;  c,  stunted  inde.\  finger;  J,  middle  finger;  r,  ring  linger;/, 
little  finger. 

Fig.  401.— Skeleton  of  the  hand  (perochirus)  shown  in  Fig.  400.  seen  from  tb<'  (i(:r>«i!  s|.I«>.  (AfUT  Olto.) 
a-f,  as  in  Fig.  400;  y,  ulna  ;  h,  radius  ;  ;.  os  naviculare  ;  ,'.  os  lunatum  :  J,  os  iriangiilarc ;  '.,  os  pl.slfonuf . 
5CS,  OS  multangulum  majus  superfluum ;  oh,  os  multangulum  ordinarium  ;  0,  os  multanguluui  minus ;  7,  os 
capitatum  ;  8,  os  hamatum. 


528 


DISTURBANCES    OF    DEyELOP:\IEXT. 


(9)  Absence  of  iiidirtdual  hones  may  oct'ur  in  any  part  of  the  oxtreini- 
ties  (Fig.  397).  ' 

(10)  reroilaet'jllsm — stunting  of  the  fingers  or  toes — appears  in  a  great 
variety  of  tornis,  but  in  general  is  seen  as  a  defective  development 
{hraehiiphaluHgism)  or  complete  absence  of  individual  jihalauges  (Figs. 
397,  399,  401,  c),  or  as  membranous  (Fig.  398)  or  bony  (Figs.  399,  401, 
(/,  e)  connections  between  the  fingers  {syndaeti/lism). 

If  only  the  outer  fingers  or  toes  are  developed  while  the  middle  ones 
are  lacking,  there  arise  those  formations  (Figs.  400,  403)  designated  as 
clcf't-hdnd  and  cleft-foot  (Kiimmel).     In  more  extensive  malfornuitions 


Fig.  402.— PerfUHis 


L'ft-fi)Ot.     (After  otto.)     Right  foot.    «,  Great  toe  ;  7>,  little  toe. 


Fio.  4a^.— Skeleton  of  the  foot  in  Fig.  402, seen  from  the  dorsal  side,  a.  Great  toe;  7j,  little  toe 
rudiment  of  third  toe ;  (7,  tibia ;  e,  fibula ;  1,  talus ;  ^,  calcaneus ;  3,  os  uaviculare ;  A,  os  euneifoinie  niii 
5,  OS  cuneiforine  minus  ;  c,  os  cuneiforme  tertium ;  ",  os  cul>iforme. 


of  lh<'  fingers  there  occur  in  j^art  also  malformations  and  defects  in  the! 
region  of  the  tarsal  and  metatarsal  bones  (Fig.  403)  or  carpal  and  met:i- 
caipal  l)ones  respectively.  Tliese  malformations  ai'e  designated  respec-i 
lively  iiaperopHS  and  perochirus.  Absence  of  the  hand  or  foot  is  known; 
as  (tchtrus  or  apu><.  ' 

Literature.  i 

{Midformations  of  the  Extremities. )  i 

Abramow  u.  Rjeranow:  SirciuMibildung.     Vircli.  Arcli.,  171  Bd.,  1903.  ; 

Adrian:  Koii gen.  Humerus    u.  Femurdefekte.     B.  v.  Bruns,  xxx.,  1901  (Lit.). 
Arnold:  3Iyelocyste,  Transposition  v.  Gewebskeimen  u.  Sympodie.    Beitr.  v.  Ziegler,' 
xvi.,  18J»4.  _  I 

1891.1 


124  j 


Basch:  Uel).  d.  sog.  rUiglmutbildiuig  in  d.  Kniekehle.  Zeitsdir.  f.  Ileilk.,  xii.,  16 
Borner:  Anat.  I'nters.  eines  Kindes  mil  Pliokomelic.  Tnaim-.-Diss.,  ]\rarburg,  1887 
Brunner:  Genese,   eongen.  3Iangel   u.  rudim.  IJiiduiii;-  d.  Patella.     Virch.   Arcli., 

Burckhardt:    Knocliendefecto  am   Vonlerarm  u.  Unterschenkel.     Jalirb.   f.  Kinder-' 

licilk.,  ;{1  Bd..  1890. 
Dareste,  C. :  :Me)u.  sur  les  anomalie.s  des  mcmbres.     Jonrn.  de  I'anat   et  do  la  phvs.  ' 

1 SS3.  ^    •     '  i 

Ehrlich:  Congen,  Defecte  n.  Hemmungsbildungcu  d.  Extremitilteu.     Virch.   Arch.,! 
mo  Bd.,  1.S85. 


I 


ABNORMAL    POSITIOX    OF    KXTREMITIES.  520 

Fischer:  C'dngt'ii.  Deft'cthiklung  an  d.  Untm'xlrciuiiril  cinrssichciij.  Knalicn,  Kostock, 

ISSO. 
Fricke:  Ucbcr  congou.  Defect  der  Fibula,  Bonn.  1SS7. 
Gebhardt;    Ein  Beitrag  zur   Anatoniie  der   Sirenenbildungnen   (cunlains   aiialuniicai 

study  of  Figs.  384  and  385).     Anli.  f.  Anat.  ii.  Pliys..  18^8. 
Goldmaiin:  Bcitr.    z.    Lelire   v.    d.    ^lissbilil.    il.   Extivniitaten.     ]5citr.  v.  I'.nms,  vii.. 

ISill. 
Grisson:   DflVct  d.  Obeisclu'nkcldiaplivsc.     Lan<;enlicck"s  Arcli  .  4!t  lid..  ls».(4. 
Gruber;  Ddeite  d.  Hand.     Arch.   f.  Anat.,  1803;  Dvfvri  dcs  IJadius.     Viich.  Anh., 

;;0.  40  I5d.,  1861. 
Hlavaceck;  Extiemitiltenmissbilduugen.     Dent.  Zeilsclir.  f.  ("liir.,  43  15(1.,  IsOd. 
Joachimsthal :  Defecto  langer  liohrenknoclien.     Dcut.   nicd.    Wocli.,    isit.");  IJracliv- 

dactviic  u.  Hyperphalangie.     Yircli.  Arcli.,  ini  JJd.,  1898;  Die  anircl).  V.rhildung 

d   ol").  Extremitateu,  Hamburg,  1900. 
Klaussner:  Die  ^lissbildungen  der  nienscld.  Gliedniaassen,  "Wiesbaden,  1900. 
Kiimmel:   Die  Missl)il(lungen  d.  Extrenutiiten,  Kassel,  189'). 
Lotheissen:  Mangel  d.  Ubersclienkelknoclien.     Beitr.  v.  Bruns,  xxiii.,  1899. 
Mayer:  Spaltlianil  u.  Spaltfuss.     Beitr.  v.  Ziegler,  xxiii.,  1898. 
Melde:   Defect  der  Tibia  u.  Polydaktylie.     luaug.-Diss.,  Marburg,  1892. 
Mies:  Angeb.  Mangel  des  V.  Fingers  u.  Mittelhandknochens.     Vircli.  Arch.,  121  Bd., 

1S90. 
Otto:  L.  c.  ^  129. 

Paster,  :Missbildung  der  Hiinde  uud  Fiisse.     Virch.  Arch.,  104  Bd.,  188G. 
Pauly:  ^laniiel   der  Diaphj-se   u.  der  imteren  Epiphvse  d.   Tibia.      i>an<:eiib.   Arcli., 

xxiv.,  18"79. 
Pfitzner:  Brachyphalaugie.     Verb.  d.  anat.  Ges.,  1898. 
Poelchau;  Ein  Fall  vou'Perodaktylie.     Inaug.-Diss.,  KiJnig.sberg.  1891. 
Rascb  :  Syndactylie  und  Polydactylie.     Beitr.  v.  Bruns,  xviii.,  1897. 
Rennert:  Beitr.  zur  Kenutniss  v.  d.  Missbildungeu  der  Extreinitilten,  Leipzig,  1882. 
Ruge:  Sirenenbilduug.     Virch.  Arcli.,  129  Bd.,  1892. 

Schafer:  Coniieu.  Defecte  von  Hauden  und  Flisseu.     Beitr.  v.  Bruns,  vii.,  1891. 
Steinhaus:  Cougenitaler  Tibiadefect.     Virch.  Arch.,  163  Bd.,  1901. 
Steinthal:  Ueber  angeb.  Mangel  einzelner  Zehen.     Virch.  Arch.,  109  Bd.,  1887. 
Strieker:  Feber  angeb.  Defect  des  Radius.     Virch.  Arch.,  31  Bd.,  1864. 
Teacher  and  Coats:  Siren-malformation.     Journ.  of  Path.,  iii.,  1895. 
Tsehudi:  Vrllst.  Verwachsung  aller  5  Finger.     Zeitschr.  f.  Chir.,  35  Bd  ,  1893. 

^  139.  Among  the  abnormal  positions  of  the  extremities  congenital 
luxations  (slipping  of  the  articular  heads  from  their  sockets)  are  (d'  «-s- 
]ieeial  interest.  They  are  most  common  at  the  hip-joint,  more  rare  at  the 
elboAv-,  shoulder-  and  knee-joints.  According  to  ^•on  Amnion,  (Jrawitz, 
Kronlein,  and  Holtznmnn,  the  congenital  Inxations  are  in  part  due  to 
I nc(tl  (imntii  of  development,  but  may  also  be  tlu' icsult  of  mechanical  in- 
tlucnces.  In  the  case  of  the  hip-joint  th«' disturbance  of  dext'lopment 
ifsnlts  in  a  small  and  imperfect  acetabular  socket,  and  the  liciid  of  the 
I't'iuur  is  usually  more  or  less  imperfectly  de\el()ped.  The  small  acclai*- 
uliim  lies  ill  the  normal  position,  but  the  head  of  the  feiiuii'  is  displaced, 
iiio.st  often  backward  (luxatio  iliaca).  At  biith  the  ligament nm  teres  is 
always  intact,  and  the  capsule  of  the  joint  covers  both  the  head  of  the 
lemur  and  the  acetalmlum.  After  much  use  of  the  leg  the  liganienlui:i 
teres  becomes  stretched  and  may  tear,  the  capsule  becomes  dilated  and 
Iiag-like,  and  at  the  point  whei-e  it  is  pressed  against  the  bone  may  be- 
'■oiae  iieiforated.  A  ne\v  joint  may  then  lie  formed  through  the  jtrolif- 
'1  at  ion  of  the  suri-ounding  ti:-;stie.s. 

Abnormal  positions  of  the  feet  and  hands  are  to  be  lelerred  ])arlly 
to  <li.sturbaiiees  of  develo])inenl  and  ])artly  to  meelianieal  inliuenees 
exerted  n])on  the  extremities  (hiring  theii-  growth.  The  most  imi)orl;int 
is  congenital  club=foot  (pes  equinovarus  i,  which,  according  to  lOsch- 
1  iclit,  is  to  be  refencd  to  an  arrest  of  d«"veloi)ment,  by  which  the  foot  is 
left  in  the  fu'tal  po.sition,  with  accompanying  abnormal  devehtpment  of 
the  bones  and  their  articular  surfaces.  The  inner  l»or<l<'r  of  the  foot  is 
34 


530  DISTI'RBAXCES    OF    DEVELOPMENT. 

sharply  elevated,  and  the  foot  at  the  same  time  brought  into  j^lantar 
flexion'.  Tlie  eollum  tali  is  elongated  in  an  anterior  and  inferior  diree- 
tiou  (Hiiter,  Adams).  If  the  children  thus  afilicted  learn  to  walk,  they 
tread  upon  the  outer  side  of  the  foot,  which  thereby  becomes  flattened, 
while  the  foot  becomes  still  more  sharply  turned  inward. 

Congenital  club-foot,  though  usually  to  be  regarded  as  a  primary  dis- 
turbance of  development  of  the  affected  joint,  may  also  under  certain 
conditions  be  caused  by  an  ahnormal  jyressure  due  to  a  relatively  small 
uterus  (Yolkmann).  Under  these  conditions  develop  also  those  patho- 
logical positions  of  the  foot  known  as  pes  calcaneus  and  pes  valgus, 
which  are  characterized  partly  by  strong  dorsal  flexion  and  partly  by 
an  outward  twisting  of  the  foot.  Frequently  the  evidences  of  the  i^ress- 
ure  to  which  the  feet  have  been  subjected  are  seen  in  an  atrophic  con- 
dition of  the  skin  and  portions  of  the  bones. 

The  position  of  the  hand  known  as  clubbed-hand  or  talipomanus  is 
caused  by  a  rudimentary  development  of  the  radius,  and  is  usually  asso- 
ciated with  other  malformations. 

Literature. 

{Changes  of  Position  of  the  Extremities.) 

V.  Ammon:   Die  congen   chir.  Krankh.  d.  Menschen,  Berlin,  1842. 
Bessel-Hag-en:  Pathologie  u.  Therapie  des  Klunipfusses,  Heidelberg,  1889. 
Debersaques:    Pathogenie  du  pied  bot  congen.     Ann.  de  la  Soc.  de  med.  de  Gand, 

1S91. 
Dolling-er:    Congenitale  luxation.     Langenbeck's  Arch.,  xx.,   1877. 
Grawitz:  Ursachen  d.  angeb.  Hiiftgelenkverrenkungen.     Yirch.  Arch.,  7-1  Bd.,  1S7S. 
Hirsch:  Die  Entstehung  d.  angeb.  Hiiftverrenkung.     Virch.  Arch.,  3  48   Bd.,  1897. 
Hell:  Plattfuss.     Langenbeck's  Arch.,  xxv.,  1880. 

Holtzmann.:  Die  Entstehung  d.  congen.  Luxationen.     Virch.  Arch.,  140  Bd.,  1895. 
Joachimsthal:  Hiiftverrenkung.     Eulenburg's  Jahrb.,  ii.,  1902. 
Kirmisson:  ('hirurg.  Krankheiten  angeb.  Ursprungs,  Stuttgart,  1899. 
Kocher:   Klumpfuss.     Deut.  Zeitschr.f.  Chir.,  ix.,  1870. 
Kronlein:  Luxationen.     Deut.  Chir.,  26  Lief.,  1882. 

Lorenz:   Pathologie  u.  Therapie  der  angeb.  Hiiftverrenkung,  Wien,  1895. 
Messner:  Knochenverand.  bei  Pes  calcaneus  congen.    Arch.  f.  klin.  Chir.,  42  Bd.,  1892. 
Michaud:  Pied  bot  congenital.     Arch,  de  phys.,  iii.,  1870. 
Miiller:    Congen.  Luxation  ira  Knie.     Arb.  a.  d.  chir.  Universitiitspolikl.  in   Leipzig, 

1888. 
Pauly:   Plattfuss.     Langenbeck's  Arch.,  xxiv.,  1879. 
Sonnenburg':  Klumpfuss.     Realencyklop.  d.  med.  "Wissensch.,  1896  (Lit.). 

2.  Abnormal  Position  of  the  Ixtekxal  Oegaxs  and  of  the 
Extremities. 

g  140.  Of  the  abnormal  positions  of  the  internal  organs,  the  most  im- 
l)ortant  is  the  one  known  as  situs  inversus  viscerum— i.e.,  a  lateral 
transposition  of  the  internal  organs,  so  tliat  the  position  of  the  thoracic  and 
alxlominal  oi-gans  forms  a  niiiror-image  of  the  normal  position.  This 
condition  lias  been  observed  both  in  double  monsters  and  in  single  indi- 
viduals. It  may  be  restricted  to  the  heart  alone,  or  to  the  abdominal 
organs,  or  more  rarely  to  a  part  of  the  latter  (situs  irregularis),  but  the 
last  is  rare.  lu  general,  abnormal  i^ositions  occur  especially  in  the  case 
of  the  abdominal  organs.     For  example,  the  kidney  is  not  infrequently 


MALFORMATIONS    DUE    TO    EXCESSIVE    GHOWTII.  5;U 

found  iu  an  abnormal  position  (^ili/sfojyia  renis),  usually  abnormally  low, 
so  that  it  approae'lu's  t.ic  s.u-ral  proiiitnilory  or  lies  in  iront  of  llie^sanu'. 
The  testis  is  not  rarely  retained  wiliiiii  the  abdominal  eavily  (rrtopia  in- 
terna, or  abdominalis  testis,  or  cn/ptorcliismtis),  or  within  llie  iii<>iiinal  canal 
(ectopia  i)iffui)ialis),  or  at  the  external  rino-  (ectopia  pultica),  or  in  the 
fold  between  the  thifih  and  scrotnm  (ectopia  rriiroscrofali.s),  oi-  in  the  peri- 
Heal  region  (ectopia  perinealis),  or  in  the  fold  of  the  groin  (ectopia  cru- 
nilis).  Abnormal  positions  of  the  intestines,  particularl>"  of  the  colon,  are 
not  rare. 


{Situs  Inversus.) 

Allmaras:  Ein  Fall  v.  Situs  transversus  partialis.     I.-D.,  Freihurjz;,  i.  Br.,  1904, 

Arneill:  Transposition  of  the  Viscera.     Amer.  Jour,  of  Med.  fcjc,  1902. 

Buhl:  Transposition  d.  Eingeweide.      Mitteil.  a.  d.  path.  Inst,  zu  Miinchen,  1878. 

Geipel:  Situs  trausverus.  Festschr.  z.  50-jahr.  Bestehen  des  Krankenhauses,  Dres- 
den, 1899. 

Kipper:  iSitus  transversus.    I.-D.,  Marburg,  1896. 

Keller:   Situs  viscerum  inversus.     Virch.  Arch.,  156  Bd.,  1899. 

Kuchenmeistei':  Die  angeb.  vollst.  ^'erlage^ung  d.  Eingeweide  d.  ^Menschcn,  Leipzig, 
1883. 

Lochte:  Zur.  Kenntn.  d.  Situs  transversus  partialis.  Beitr.  v.  Ziegler,  xvi.,  1894; 
Situs  viscerum  irregularis.    lb.,  xxiv.,  1898. 

Martinotti:  Delia  transposizione  laterale  dei  visceri,  Bologna,  1888. 

Wehn:  Zur  Frage  d.  Situs  transversus.      Virch.  Arch.,  98  Bd.,  1S84. 

3.  Malformations  due  to  Excessive  Growth  or  Multiplica- 
tions OF  Organs  or  Body-parts. 

§  141.  The  malformation  known  as  general  giant  growth  occurs  as 
the  result  of  an  excessive  growth  of  the  entiie  body,  either  daring  intra- 
uterine life  or  later.  During extra-nterine  life  such  an  abnormal  giowth 
may  occnr  that  the  size  of  the  affected  individual  may  far  exceed  the 
maxinnim  normal  limits. 

Partial  giant  growth  may  also  take  place  dniiug  intra-nterint;  life  or 
after  birth.  The  head  and  portions  of  the  extremities  ai'e  usnally  af- 
fected. A  unilateral  giant  growth  is  usually  restricted  to  the  half  of  the 
face  or  to  one  extremity,  bnt  in  very  rare  cases  the  hypci'trophy  may  in- 
volve all  the  parts  of  one  side:  face,  trunk,  and  extremities.  In  extra- 
uterine life  trauma  sometimes  gives  the  impnlse  to  a  pathological  excess 
9f  growth. 

Should  the  other  tissues  become  so  increased  in  any  portion  of  the  body, 
the  extiemities,  the  trunk,  or  face,  that  malformations  le.sembling  the 
skin  of  the  pachyderms  are  produced,  thealmormal  growth  is  designated 
elephantiasis  (see  §  76,  Figs.  l.'JO,  181).  The  inci-ease  in  mass  may  de- 
pend upon  a  new-formation  of  connective;  tissue  or  adipose  tissue;  or  of 
blood-vessels  or  of  lymphatics.  When  the  thickened  regions  ai<'  shai'ply 
circumscribed  the  formation  is  regaidccl  as  a  tumor  and,  accoidiug  to  its 
Structure,  is  classed  with  the  angiomata,  lymphangioniata,  or  iibroiuata 
(see  sections  treating  of  these  tumors). 

Circumscribed  hypertrophies  of  the  bones  occui*  in  Aaiious  ])ortions 
of  the  skeleton,  and  are  sometimes  multi])le.  The  bones  of  the  skull 
as  well  as  those  of  the  face  may  be  thus  atfected,  and  llu're  occnr  ca.ses 
in  which  the  hypertrophy  of  the  bone  may  be;  so  exlcnsiv o  that  one  or 


532  DISTURBANCES  OF  DEVELOPMENT- 

both  of  these  regions  may  show  marked  clisfigiiratioD,  and  there  aie  pro- 
duced conditions  m  hich  are  known  under  the  general  term  of  leontiasis 
ossea  (Fig.  137\  Circumscribed  hypertrophies  of  the  bones  lead  to  the 
formation  of  osteomata  or  exostoses,  which  are  often  multiple.  On  the 
trunk  and  extremities  local  growths  of  bone  may  lead  to  the  enlargement 
of  single  bones  as  well  as  to  the  formation  of  atypical  excrescences 
kuowu  as  osteomata  and  exostoses,  which  are  not  infrequently  multiple. 

Literature.  I 

(Gia)ifism.)  ! 

Andersen;  Riesenwuchs  der  Extremitiiteu.     St.  Thorn.  Hosp.  Rep.,  London,  1882.       ' 
Ai-nheim:  Congeuitale  lialbseitige  Hypertrophie.     Vircli.  Arch.,  lo6Bd.,  1898  (Lit.). 
Bessel-Hagen:  Part.  Riesenwuchs  u.  multiple   Exostosen.  Langenbeck's  Arch.,  41  ■ 

Bd.,  1891. 
Buhl :  Ein  Riese  mit  Hyperostose.     Mitth.  a.  d.  path.  Inst,    ]\Iiinchen,  1878. 
Busch:  Riesenwuclis  der  Extremitaten.     Arch.  f.  klin.  Chir.,  vii.,  1866. 
Curling:  Riesenwuchs  der  Finger.     Med. -Chir.  Trans.,  xxviii.,  1845. 
Ewald:  Hypertrophie  der  Hand.     Virch.  Arch..  36  Bd,  1873. 
Fischer:  Riesenwuclis  der  Extremitaten.     Dent.  Zeitschr.  f.  Chir.,  xii.,  1880. 
Frankel:  jMakrosomia.     Virch.  Arch  ,  46  Bd.,  1869. 

Friedberg-.  Riesenwuchs  der  Extremitaten.     lb.,  40  Bd.,  1867.  i 

Friedrich:     Ilalbseitige  cougenitale  Kopfhypertrophie.     lb.,  28  Bd.,  1863.  > 

Gruber:  :\Iakr<)d:iktvlie.     lb.,  36  Bd.,  1872.  | 

Hals:  -Maknnlaklvlie.     D.  Zeitschr.  f.  Chir.,  37  Bd.,  1S93  1 

Little-  Ri-'scnwuchs  der  Extremitaten.     Trans.  Path.  Soc,  1866.  1 

Trelat  ct  Monod:  De  I'liypertrophie  unilaterale.     Arch.  gen.  de  med.,  1869.  j 

Vierordt,  II.:  Anatom.,  physiol.  u.  physikal.  Dateu  u.  Tabellen,  Jena.  1893 

See  also  J^  76. 

§  142.  The  occurrence  of  supernumerary  organs,  or  of  a  niultipli= 
cation  of  parts  of  the  skeleton,  and  of  the  muscular  system,  is  relatively! 
frequent.  Such  phenomena  are  to  be  atti'ibuted  in  part  to  a  cleavage  or) 
multiple  appearance  of  the  given  aiilage,  and  in  part  to  a  more  markerlj 
de\elopment  or  persistence  of  organs  which  normally  remain  in  a  rudi-i 
nientary  state,  or  undergo  retrogression  during  the  jieriod  of  growth.! 
Further,  certain  of  the  conditions  included  under  this  head  may  be  re-i 
garded  as  reversions. 

1.  Duplications  of  the  extremities.     A  duplication  of  an  entire  ex 
tremity  withont  the  duplication  of  the  pelvic  or  shoulder  bones  has  not; 
been  observed  in  man.     Duplication  of  the  hands  and  feet  is  very  rare. 
(Fig.  404),  but  a  number  of  cases  are  reported  in  the  literature.     The. 
mimber  of  fingeis  may  reach  nine  or  ten.  \ 

Much  more  frequent  is  a  multiplication  of  the  fingers  (polydactyl, 
ism)  on  a  single  hand  (or  foot  respectively),  in  which  condition  the  super-j 
numerary  fingers  (or  toes)  are  attached  in  part  at  the  ulnar  or  radial  side 
(or  tibial  and  iibular  sides  respectively),  or  in  part  intercalated  betweer.j 
llie  others  (Figs.  401,  «;  405).  Often  the  fingers  are  duplicated  only  in 
l)art— that  is,  by  the  cleavage  of  the  first  or  the  first  and  second  terminal 
joints  (Fig.s.  400,  407).  Those  attached  at  the  margin  of  the  hand  ma> 
be  well  developed  (Fig.  40.j)or  rudimentary.  Occasionally  they  appeal 
as  small  pedunculated  fibrous  tumors.  In  the  fully  developed  super 
nnmerai-y  fingers  or  toes  the  phalanges  (Fig.  405)  may  articulate  will 
the  metacarpal  or  metatarsal  bones  of  a  neighboring  finger  or  toe,  orwitlj 
their  own  (.snpeiiiumeiary )  carpal  or  tarsal  bones  (Fig.  401,  5a).  Polyi 
dactyli.sm  in  certain  ca.^es  is  inherited  and  is  therefore  dependent  upoi 


I 


POLYDACTYLISM    AM)    SYM)A(    T^  LISM. 


):53 


intrinsic   causes.     In   individual  cases  i^olydactylism  occurs   :is  ;iii    ii 
iieritable  condition  and  is  therefore  dependent  n])on  inlrinsic  cumscs. 


FIG.  404.  Fifi.  4(15. 

Fig.  4(M.— Polydactylism  with  forking  of  the  hand.    (After  Laneereau.x.) 

Fig.  405.— Pol.vdaetylism  in  a  new-born  child.    Skeleton.    Duplication  of  the  phalan^res  of  the  fourth 
and  fifth  lingers.    Natural  size. 


Fig.  4(Mi.  Fk;.  407. 

Fig.  406.— Polydactylism  and  syndactylism  of  the  left  hand.    Reduced  one-Ilfth. 
Fig.  407.— Polydactylism  and  syndactylism  of  the  right  foot.    Reduced  one-llfth. 


534  DISTURBAXCES  OF  DEVELOPMENT. 

2.  Supernumerary  nipples  and  breasts  (hyperthelia,  hyper- 
mastJa)  aiv  not  imcoiuiuoii  inairormatioiiS  in  both  sexes,  and  are  prob- 
ably to  be  regarded  as  a  reversion  to  polymastic  racial  ancestors.  The 
supernumerary  organs  are  usually  situated  on  the  thorax,  along  two  lines 
converging  from  the  axillary  to  the  inguinal  regions,  but  in  lare  cases 
they  may  be  found  elsewhere — in  the  axilla,  on  the  shoulder,  on  the 
abdomen,  back  or  thigh.  They  are  usually  small,  but  in  the  event  of 
pregnancy  may  take  on  functional  activity.  The  number  of  the  nipples 
may  reach  as  high  as  ten. 

.">.  The  formation  in  men  of  breasts  resembling  those  of  women 
(gynaecomastia)  is  rarely  seen  in  well-developed  men  with  normal  sex- 
ual apparatus  (see  Hermaphrodism,  g  143),  but  it  not  infrequently  hap- 
pens that  the  male  breast  undergoes  a  moderate  enlargement  at  the  time 
of  puberty. 

4.  Duplication  of  the  penis  is  of  very  rare  occurrence,  and  may  be 
associated  with  the  formation  of  two  urethr?e  having  independent  open- 
ings into  the  bladder,  and  with  two  scrota,  the  two  penises  being  typi- 
cally develo])ed  (Lange). 

5.  Supernumerary  bones  and  muscles  are  of  frequent  occurrence. 
Siipermoiicidri/  vertebrw  may  be  found  in  any  part  of  the  spinal  column; 
and  at  its  lower  end  may  in  rare  cases  cause  a  lengthening  of  the  column, 
resulting  in  the  formation  of  a  tail.  According  to  Virchow,  three  forms 
of  tails  may  be  distinguished :  true  tails  containing  bones ;  false  or  im- 
perfect tails  which  represent  an  elongation  of  the  vertebral  column, 
but  contain  neither  cartilage  nor  bones  (so-called  pig's-tail) ;  and  tail-like 
appendages  of  skin  which  consist  of  different  forms  of  tissue,  and  in  part 
are  to  be  classed  with  the  teratomata.  The  true  tails  are  very  rare;  ac- 
cording to  Bartels,  they  are  more  often  the  result  of  a  separation  or 
elongation  of  the  ^•ertebr{e  than  of  an  increase  in  their  number. 

Eeduplication  of  the  phalanges  of  one  finger  is  very  rare. 

SupcruiDiierari/  ribs  in  the  neck  or  lumbar  region,  as  well  as  a  forking 
of  the  ril>s,  arc  not  lare. 

tSujX'ni  11  III (■)■(( ri/  teeth  also  occur. 

().  Duplication  oi-  cleavage  of  the  aniage  of  the  thoracic  and  abdom- 
inal organs  occurs  most  frequently  in  the  case  of  the  spleen,  pancreas 
adrenals,  ureters,  jjelvis  of  the  kidneys,  and  lungs,  more  rarely  in  case 
of  the  ovary,  liver,  kidney,  testicle,  and  bladder. 


Literature. 

{Supernumerary , Organs  or  Parts.) 


w 


D'Adjutolo:  Coutrib.  alio  studio  delle  varietil  uumeriche  delle  vertebre.    11  Morgagni, 
xxx-.,  1S88.  1 

Ballowitz:  Wcicbtoile  bci  Ilypcrdaktylie.     Virch.  Arch.,  178  Bd.,  1904, 
Bartels:  Scliwaiizbilduug.     Arch,  f    Anthrop.,  15  Bd.,  1884. 
Boinet:  Polydactylie  et  atavLsmc.     Eev.  aemed.,  xviii.,1898. 
Bonnet:  Die  Maiiiinaorgane.     Ergebn.  d.  Anal.,  ii.,  Wiesbaden,  1893. 
Buschan:  Poiyinastie.     Eiilenburg's  Realencyklop.,  xix.,  1898  (Lit.). 
Ecker:   8ch\vaiizbil(lung.    Arch.  f.  Anthrop., "xi.;  Arch.  f.  Anat.,  1880. 
Freund:  Scinvanzbildungbcim  Menschon.     Virch.  Arch.,  104  Bd.,  1886. 
Gegenbaur:  Krit.  Bemerkungeu  uber  Poly  dak  ty  lie  als  Atavismus.    Morpli.  Jahrb. 

ISHO. 

Gerlach:  Schwanzbildung.     Morph.  Jahrb..  vi. 

Hagenbach:  Angel).  iSacrococcyirealtumoren.    A.  f.  klin.  Chir.,  66  Bd.,  1903. 

Harrison:  Tails  ill  Man.    .Johns  Hopkins  Hosp    Bull.,  xii.,  1901. 

Hennigu.  Rauber:  Ein  Fall  von  geschwanztem  Menschen.     Virch.  Arch.,  105  Bd.,| 

1«80. 


HEKMAPIIHODISM.  5;i5 

Joachimsthal :  Hyperphalan'rie.     Virch.   Arch.,  l.")l  lid.;  Die  an>,'cl).  Vcrbild.  d.  ob. 

Kxtivniitat,  Hamburg-,  1900. 
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ISOl. 
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IS!):. 

KoUmann.  Ilandskelet  u.  Ilyperdaktylie.     Aiiat.  An/..,  iii.,  ISSS. 

Kiittner;  VcrtldpiK-hinj?  dcs  IVnis.     Beitr.  v.  Bruns,  xv.,  1890. 

Lange:  Coinidrtc  Vi'rdoppclung  dos  Penis.     Bcilr.  v.  Ziegler,  xxiv.,  1898  (Lit.). 

Laurent:  Lcs  bisexiu's,  gyuecouiastes  ct  licrmaplirodites,  Paris,  1S94. 

Leichtenstern :  iSuperuumerare  Brilste  u.   Brustwarzcu.     Vircli.  Arcli.,  7:5  Bd.,  1878 

(\M.). 
Levin;   L'cberziilil.  kleiue  Finger.     Vircli.  Arch.,  142  Bd.,  189o. 
Lissner:  Schwauzbilduug  beim  Meuschen.     Virch.  Arch.,  99  Bd.,  1887. 
Neugebauer:  Polymastie  mit  10  Brustwarzcn.     Cbl.  f.  Gvn  ,  188();  3.")  Fiiile  v.  Vcr- 

dopp.  d   iiuss.  Genitalicn.     ]Monatsschr.  t'.  Gcbh.,  vii.,  1897. 
Otto:   .Monstroruni  sfxccntonun  dcsciiptio  anatoniica,  1844. 
Pfitzner:   Doiipclbildung  d.  5  Zchc.    ALorjih.  Arb.,  1893;  Vcrdoppching  d.  Zcigcfingcrs. 

11)..  vii.,  1897:  Missbild.  d.  Extremltiitenskelets.     lb.,  viii.,  1898. 
Piatnisky;  Ban  des  meuschlichen  Schwanzes.     Inaug.-Diss.,  Petersburg;  Anat.  Anz., 

viii.,  1893. 
Schmidt:  Normale  Hyperthelie  menschl.  Embryonen.     Anat.  Auz.,  xi.,  1890. 
Sell:  Hvperthelie,  Hvpermastie  u.   Gyuakomas'tie.     Ber.  d.   Naturf.   Ges.,  Freiburg, 

ix., '1894  (Lit.). 
Stieda:  Gyuilkomastie.     Beitr.  v.  Bruns,  xiv.,189o. 

Stahr;  Congeu.    Tumor  am  kl.  Finger.     Virch.  Arch.,  151  Bd.,  Suppl  ,  1898. 
Virchow:  Schwauzbilduug.     Deut.  med.  Woch.,  1884. 
Viorin:  Polydaktylie  bei  Ungulaten.     Z.  f.  Tiermed.,  vi.,  1902. 
Wiedersheim :  Der  Bau  des  Meuschen,  Freiburg  i.  B.,  1902. 
Zander:  1st  die  Polj'daktylie  therouior])he  Varietiit  oder  ]Missbildung?     Virch.  Arch., 

125  Bd.,  1891. 

4.  True  and  False  Hermaphrodism. 

§  143.  The  fact  that  tlie  sexual  organs,  both  the  sexual  glands  and 
the  external  genitals,  of  both  sexes,  develop  from  originally  similar 
anlage  which  contain  the  beginnings  of  all  the  sexual  oi-gaiis  of  both 
sexes,  makes  it  apriori  probable  thatmalfonnatioiisniighl  icsuit  tlirongh 
unequal  development  of  the  anlage  of  the  right  and  left  sides,  orthiough 
a  simultaneous  development  of  organs  peculiar  to  both  sexes,  or  linally 
through  a  lack  of  harmonious  development  of  the  external  and  internal 
genitals. 

Those  malformations  which  are  to  be  rc^ferred  to  some  one  of  the  factors 
named,  andM'hich  are  characterized,  by  the  fact  that  the  sexual  ai)paratus 
of  a  single  individual  contains  parts  belonging  to  IhiIIi  the  male  and 
female,  arc  grouped  under  the  designation  hermaphrodismus.  ^\'h(•n 
both  sexual  glands  (testis  and  ovaiy)  aie  present  the  condition  is  called 
hermaphrodismus  verus  [hcrmaphi-odismuH  f//(in(h(l<(ri.s,  Siegenbeck  ^an 
lleukelom).  If  the  mixing  of  sexual  charactei'istics  consists  nierely  of  a 
combination  of  male  and  female  gt^nital  passages  Mith  the  external  geni- 
talia of  the  opposite  sex,  the  condition  is  known  as  pseudohermaphro- 
dismus.     The  ti'ue  sex  is  determined  by  the  nature  t»f  the  se\u;d  ghind.s. 

The  body  build  of  hermaphrodites fi'equently  shows  acuri(»us  mi.\lure 
of  male  and  female  cliaracteristics.  For  example,  the  breasts,  neck,  an<l 
shoulders  may  correspond  to  the  fennile  tyj.e,  while  this  de\  elopment  of 
the  beard,  face,  larynx,  and  voice  may  correspond  to  the  male  type.  In 
false  hermaphrodites  the  body  characteristics  do  not  always  correspond 
to  the  true  nature  of  the  sexual  glands;  a  male  may  resendile  a  female, 
and  vice  versa. 


536 


DISTX'RBAXCES    OF    DEVELOPMENT. 


The  following  chief  types  of  hermaphrodism  maybe  distinguislied : 

1.  Hermaphrodismus  varus  or  androgynes. — 1.  Hermaphrodismus  verus  hi- 
lateralis,  or  double-sided  hermaphrodism,  is  characterized  by  the  presence  on  l^oth 
sides  of  both  ovary  and  testis,  or  the  presence  on  both  sides  of  an  organ  containing  both 
ovarian  and  testicular  tissue.  Heppner  asserts  that  in  a  nine-rr.onths-old  child,  having 
hermaphroditic  external  genitals,  with  vagina,  uterus,  and  tubes,  both  ovary  and 
testis  were  found  in  the  broad  ligament;   epididymis  and  vas  deferens  were  wanting. 

2.  Hermaphrodismus  verus  unilateralis ,  or  one-sided  hermaphrodism,  is  that  con- 
dition in  which  upon  one  side  there  exists  but  one  sexual  gland,  while  on  the  other 
both  testis  and  ovary  are  present.  Sak'n  has  reported  a  case  of  a  woman  of  forty-three 
years  of  age,  who  had  menstruated  since  her  seventeenth  year,  in  whom  there  was 
iound  upon  the  right  side  (castration  on  account  of  uterine  myoma)  a  hermai^hroditio 


Fifi.  408. —Hermaphrodismus  verus  lateralis.  (After  Obolonsky.)  a.  Urethra:  7),  prostate;  r,  colliculus 
seminalis;  »?,  hymen;  c,  ciinalis  urogenitalis ;  /,  bladder;  g,  vagina;  /i,  uterus;  h,,  left  uterine  horn;  /, 
left  tube;  (',,  infuudibuUiiii  of  left  tube;  /f,  left  ovary;  ?,  ligamentum  ovarii;  »)i,  liganientum  teres  sin- 
istnuii;  ?i,  right  tube;  o,  right  testicle ;  j>,  epididymis ;  (/,  right  vas  deferens ;  r,  lisjamentum  teres  dextrum. 
About  one-half  natural  size.  (Specimen  in  the  collection  of  the  Pathological  Institute  of  the  German  Uni. 
versity  in  Prague.) 

gland,  the  nature  of  which  was  confirmed  by  accurate  microscopical  examination.  The 
ovarian  portion  of  the  gland  was  typically  developed;  the  epithelium  of  the  seminifer- 
oud  tu[)ules  of  the  testicular  portion  consisted  of  follicular  cells  and  cells  of  Sertoli, 
but  lacked  spermatogonia  and  seminal  cells.  Blacker  and  Lawrence  have  also  de- 
scribed a  case  of  hermaphroditic  gland  occurring  in  a  child  still-born  at  eight  and  a 
half  months.  In  the  hernial  sac  of  an  individual  twenty  years  old  Gam'  demonstrated 
the  presence  of  a  tube  and  both  sexual  glands  with  parovarium  and  epididymis  (the 
microscopical  examination  was  made  by  Simon). 

3.  Hermaphrodismus  verus  lateralis  is  that  condition  in  which  there  is  an  ovary  on 
one  side  and  a  testis  on  the  other.  It  has  been  many  times  observed  in  man  (Rudolph, 
Stark,  Berthold,  Barkow,  II.  Meyers,  Klebs,  Messner,  Kcllner,  and  others),  though  in 
the  majority  of  cases  no  careful  microscopical  examination  was  made,  and  when  carriecl 
out,  ovarian  tissue  could  not  with  certainty  be  demonstrated.  Several  years  ago 
Oholonski/  reported  a  case  (a  twelve-year-old-girl)  from  the  collection  of  the  German 
University  in  Prague,  in  which  the  histological  examination  showed  on  the  right  side 
a  testicle  (Fig.  408,  o),  and  on  the  left  side  an  ovary  (k),  but  it  is  to  be  noted  that  ova 
were  not  seen  in  the  latter.  The  right  broad  ligainent  contained  a  testis  (o),  an  epi- 
didymis (/>),  a  vas  deferens  (q),  a  rudimentary  tube  (n),  a  round  ligament  (r);  the  left 
broad  ligament,  on  the  other  hand,  contained  an  ovary  (k),  with  an  ovarian  ligament 
(0,  ivnd  a  well-developed  tube  (i).  Moreover,  a  uterus  {h),  vagina  (<?),  and  also  a 
prostate  (6)  were  present.     According  to  the  reported  observations,  the'  corresponding 


HERMAPHKODISM. 


537 


sexual  passages  may  be  present  or  in  part  wanting.  Tiie  external  genitals  are  mal- 
formed, and  combine  structures  belonging  to  both  sexes. 

II.  Hermaphrodismus  spurius,  or  pseudohermaphrodismus,  is  characterized 
by  a  bisexual  develoijment  of  the  sexual  passages  and  external  sexual  organs  in  associa- 
tion with  a  unisexual  tlevelopment  of  the  essential  sexual  lilaiid.  The  most  pronounced 
cases  occur  in  males,  who,  in  addition  to  their  i)roi)er  sexual  organs,  possess  a  more 
or  less  AA ell-developed  vagina,  uterus,  and  tubes.  It  is  much  more  rare  to  find  in 
females  a  development  of  a  portion  of  the  Wolffian  duct. 

In  male  false  hermaphrodites  the  external  genitals  are  frequently  malformed  and 
approach  the  female  type,  while  in  female  false  hermaphrodites  the  external  genitals 
resemble  those  of  the  male  (Fig.  401)). 

The  resemblance  of  the  male  external  genitals  to  those  of  the  female  is  brought 
about  by  a  stuntins:  of  the  penis  and  a  total  or  partial  failure  of  the  sexual  furrow  ia 
the  penis  to  close  (hypospadias),  so  that  the  two  halves  of  the  scrotum  are  separated, 
leaving  a  depression  beneath  the  root  of  the  penis,  which  represents  the  remains  of  the 
sinus  urogenitalis.  The  scrotal  halves  com.e,  therefore,  to  resemble  the  labia  majora, 
particularly  in  the  case  of  non-descent  of  the  testicles.  The  external  genitals  of  the 
female  approach  in  appearance  those  of 
the  male  through  the  development  of  the 
clitoris  into  a  sort  of  penis  (Fig.  409,  a), 
while  the  vaginal  opening  is  narrowed  or 
closed  through  the  union  of  the  labia. 
The  vagina  and  urethra  have  a  com- 
mon opening,  or  open  separately  be- 
neath the  penis-like  clitoris. 

The  atypical  development  of  tb.e 
external  srenitals  may  or  may  not  Ije 
associated  with  malformations  of  the 
sexual  passages,  and  is,  therefore,  not 
dependent  upon  malformations  in  other 
portions  of  the  sexual  apparatus. 

1.  Pseudohei-maphrodismui  masculi- 
nus  occurs  in  three  varieties: 

First,  pseudohermaphrodismus  ynas- 
culinus  internus,  inwhich.  condition  the 
external  genitals  are  of  the  male  type, 
and  the  prostate  is  developed,  but  is 
usually  pierced  at  the  coUicidus  semin- 
alis  by  a  canal  opening  into  the  urethra, 
the  former  being  continued  above  into  a 
rudimentarj^  or  more  or  less  well-de- 
veloped vagina,  often  also  into  a  more 
or  less  well-formed  uterus,  and  even 
tubes.  The  male  organs  may  be  well 
developed  or  more  or  less  malformed. 

Second,  pseudohermaphrodismus  mas- 
culinus  completus,  or  externus  et  internes, 

in  which  form  the  vagina,  uterus,  and  tubesare  present  in  a  state  of  rudimentary-  or  more 
or  less  complete  development,  while  the  external  genitals  resemble  more  or  less  com- 
pletely the  female  type.  The  penis  presents  the  condition  of  hypospadias  and  resembles 
the  clitoris;  beneath  it  lies  a  furrow  at  whose  posterior  end  there  is  usually  an  orifice 
leading  into  a  short  vestibule  which  divides  at  once  into  a  urethra  and  a  vagina.  Some- 
times the  vagina  and  vestibule  are  separate.  In  rare  cases  the  external  genitals  appear 
normal,  but  the  penis  contains  a  double  canal,  the  upper  one  representing  tlie  urethra, 
the  other  the  sexual  passage.  In  the  case  of  a  more  marked  development  of  the  ducts 
of  Midler  the  vasa  deferentia  are  frequently  defective,  and  the  .seminal  vesicles  are 
sometimes  wanting. 

Third,  psewlohermaphrodismus  masculinus  externus,  in  whieli  only  the  external 
genitals  depart  from  the  male  type,  and  resemble  more  or  less  closely  the  female.  .Vs  in 
these  cases  the  bodily  habitus  often  simulates  that  of  the  female,  the  true  .sex  of  the 
individual  may  easily  be  mistaken. 

2.  Pseudohermaphrodismus  femininus  also  occurs  in  three  .similar  varieties,  l)ut  is 
much  more  rare. 

In  pseudohermaphrodismus  femininus  internus  rudiments  of  the  Wolffian  ducts, 
lying  in  the  broad  ligament  or  in  the  uterovaginal  wall,  and  sometimes  extending  to 
the  clitoris,  are  found  in  association  with  well-developed  external  genitals. 


Fig.  409.— External  genitals  of  a  female  false  her- 
maphrodite, with  stenosis  of  th*-  vaginal  orlflee.  a. 
Penis-like  clitoris  ,•  h,  labia  majoia.  Kedueed  one- 
ninth. 


538  DTSTX'RBAXCES    OF    DEVELOPMENT. 

Pseudohermaphrodismus  femininus  externus  is  characterized  by  external  genitalia 
resembling  those  of  the  male  (Fig.  409). 

Pseudohermaphrodismus  femininus  externus  et  internus,  in  which  the  external 
genitals  resemble  those  of  the  male  and  there  is  a  persistence  of  parts  of  the  Wolffian 
ducts,  is  A'ery  rare.  Of  the  internal  male  genitaha,  there  was  found  in  one  case  a  pros- 
tate, and  in  another  case  a  prostate  pierced  by  the  vagina,  an  ejaculatory  duct,  and 
a  eac  resembling  a  seminal  vesicle,  which  opened  into  the  vagina. 

Tlic  internal  sexual  organs  develop  from  the  same  undifferentiated  anlage  in  both 
males  and  females.  Tlitse  anlaue  consist  of  a  sexual  gland  lying  on  the  medial  ante 
rior  side  of  the  M'olffian  hmh/,  and  a  sexual  jiassage  known  as'tha  duct  of  Midler.  Tiie 
latter  develops  beside  the  M'oljfian  duct,  and,  like  it,  empties  into  the  lower  end  of  the 
bladder  or  into  the  sinus  urogenitalis. 

In  the  nude  the  duct  of  Miiller  disappears,  only  slight  traces  in  the  form  of  the 
uterus  masculinus  or  vesicu'la  prostatica  remaining;  the  primitive  sexual  gland  unites 
with  a  small  part  of  the  Wolffian  body,  Avhicli  becomes  the  head  of  the  epididymis, 
anotlier  small  portion  forming  the  vasa  aberrantia  testis  (organ  of  Gircddei^).  the  re- 
mainder disappears,  while  the  Wolffian  duct  becomes  the  vas  deferens  and  vesicula 
seminalis. 

In  the  female  the  Wolffian  body  and  its  duct  disappear,  leaving  only  a  trace  in  the 
form  of  the  gland-tubules  knoM'n  as  the  parovarium,  but  remains  of  tlie  duct  are  not 
infrequently  found  preserved  in  the  uterine  wall.  From  the  ducts  of  Midler,  which  in 
part  coalesce  at  their  lower  ends,  develop  the  vagina,  uterus,  and  tubes.  The  extreme 
upper  end  of  the  duct  of  Midler  not  infrequently  persists  in  the  form  of  a  little  pedicled 
sac  attached  to  the  abdominal  end  of  the  tube,  the  hydatid  of  Monjagni. 

The  anlage  of  the  sexual  glands  appear  in  the  fifth  week.  In  mammalia  (probably 
also  in  man)  they  develop  through  a  localized  thickening  of  the  peritoneal  epitheliuin, 
which  becomes  the  germinal  epithelium  (Waldeyer).  while  at  the  same  time  the  meso- 
derm also  proliferates.  Whether  the  seminal  tubules  arise  from  peritoneal  epithelium 
(Bornhaupt  Eyli),  or  whether  they  are  derived  from  a'u  ingrowth  of  the  Wolffian  body 
into  the  testis-anlage  ( Waldeyer),  is  still  an  undecided  question  {KiAliker).  The  ova 
arise  from  germinal  epithelium.  The  environing  cells  of  the  Graatian  follicle  are 
regarded  b\'  Waldeyer  a.%  &\?,o  derived  from  the  germinal  epithelium;  \i\n\e  Kolliker 
believes  that  they  probably  arise  from  the  Wolffian  body. 

The  siguidcance  of  the  i)eduncidated  and  non-pedunculated  hydatids,  found  in  vary- 
ing numbers  near  the  globus  major  of  the  epididymis,  is  not  yet  determined  {Kiilliker). 
The  non-pedunculated  cyst  known  as  the  hydatid  of  Morgagni  is  regarded  by  W(ddeytr 
as  a  renmaut  of  the  duct  of  Miiller.  According  to  lioth,  it  may  also  stand  in  a  close 
relation  to  the  Wolffian  bodj%  inasmuch  as  there  is  occasionally  found  a  vas  aberrans 
of  the  epididymis  communicating  with  it. 

In  the  development  of  the  vagina  and  uterus  the  ducts  of  Midler  and  the  Wolffian 
ducts  luiite  at  their  lower  portion  to  form  a  rounded  quadrangular  cord,  the  genital 
cord.  At  the  end  of  the  second  month  the  ducts  of  Midler  blend  to  form  a  single  canal, 
which  tiieu  develops  into  the  vagina  and  uterus.  This  union  takes  place  first  near  the 
middle  of  the  genital  cord.  The  Wolffian  ducts  play  no  role,  though  remains  of  these 
are  found  at  birth  in  the  broad  ligament  (Kolli/.er)  and  in  the  wall  of  the  uterus  (Beigel). 
According  to  observations  of  Riedel,  remains  of  the  AVolffian  duct  are  found  in  about  a 
tliird  of  adult  females,  in  the  form  of  a  tube  lined  by  cylindrical  epithelium  surrounded 
by  muscle,  or  as  a  muscle-bundle  without  epithelium,  lying  anteriorly  and  to  the  side 
of  the  uterus  and  vagina. 

The  external  genitals  begin  to  develop,  even  before  the  cloaca  has  separated  into 
the  intestinal  and  genito-urinary  orifices,  by  tlie  formation,  in  the  sixth  week,  of  a  me- 
dian genital  tubercle  in  front  of  the  cloaca,  and  further,  of  two  lateral  folds,  the  genital 
folds.  Toward  the  end  of  the  second  month  the  tubercle  becomes  more  prominent,  and 
sliows  on  its  lower  surface  a  furrow,  the  genital  furrow.  In  tlie  third  month  the  cloaca 
becomes  divided  to  form  the  anal  and  genito-urinary  openings.  In  the  male  embryo 
tiie  genital  tubercle  becomes  the  penis,  the  glans  being  recognizable  as  early  as  the 
third  month.  In  the  fourth  month  the  furrow  closes  to  form  a  tube;  at  the  same  time 
tiie  two  genital  fohls  unite  to  form  the  scrotum. 

The  prepuce  is  formed  in  the  fourth  month.  The  prostate  arises  in  the  third  month 
as  a  thickening  of  the  tissues  at  the  junction  of  the  urethra  and  the  genital  cord.  The 
glands  of  the  prostate  develop  in  the  fourth  month  from  the  epithelium  of  the  canal 
and  grow  out  into  the  surrounding  connective  tissue. 

In  the  female  embryo  the  closure  of  the  genital  furrow  and  the  genital  folds  does 
not  take  place,  so  _  that  the  sinus  urogenitalis  remains  short.  The  genital  eminence 
becomes  the  clitoris,  the  folds  become  the  labia  majora,  and  the  edges  of  the  genital 
furrow  the  labia  minora. 


HERMAPIIRODISM.  630 

Literature. 

{True  and  False  Jlennaphrodism.) 

Abel:  Pseudoliermaphrodismus  masculinus.     Vircii.  Anli..  l-^(i  IJd.,  1S!)1. 

Arnold,.!.:  Uterus  masculinus.     Vircli.  Arch..  47  15d..  ISCii). 

Becker:   Ucber  Zwitterbildun.ir.     AVlirzburiijer  Vcrli.,  l,SO(i. 

Benda.  Hermaphrodismus.     Ergebn.  d.  alli?.  PaMi.,  ii..  IS!)?. 

Blacker  and  Lawrence:  (^asc  o'f  True  Unilateral  IR'rniai)iirodisinus  with  Ovotostis  in 

Man.     Trans,  of  tin'  Obstctr.  Soc.  of  London,  xxxviii. 
Binihl:  Ucbcr  Ilcnnapiirodisnuis.     Inaug.-Diss.,  Frt-iburir,  1S{)4. 
Crecchio:  llcnnaiilnodisnius  fc.n.  extern,  et  intern.     Wieu.  nicd.  Pressc,  I8(i(). 
Debierre:  L'lierniai^hrodisnie,  Paris,  1891. 
Garre:  Eclitcr  Hcrniaiihrodisnms.     D.  nied.  AV'och.,  1903. 
Henrichsen:  Pseudolierniaplir.    niascul.  extern,  completus.     Yirch.  Anli.,    !)t    Bd., 

1SS5. 
Heppner:  Ilerniaphrodisnius  verus.     Du  Bois-Reymoud's  Arch.,  1870;  ri'f.  (hi.  f.  d. 

lucd.  Wiss.,  1571. 
Keibel:  Eutwickelungsgesch.  d.  Urogenitalapparatus.     Arch.  f.  Anat.,  189G. 
Kellner:  Ilerniaphroditismus  lateralis.    D.  nied.  Wocli.,  1902. 
Klebs:  Handb.  d.  pathol.  Auat.,  i.  Bd.,  2  Abth.,  Berlin,  1876. 
Klopsch:  Hermaphrodismus  verus  beim  Sclnveiue.     Anat.  Anz.,  xii.,  189G. 
Laurent:  Les  bisexues,  gyneconiastes  et  hermaphrodites,  Paris,  1894. 
Luksch:  Ilerniaphrodisnius  spur.  masc.  int.     Zeit.  f.  Heilk.,  xix.,  1900. 
Marchand:  Hermaphrodismus  spurius  masculinus?     Vireh.  Arch.,  92  Bd.,  1S83. 
Messner:  Ilennaphrodismus  verus.     Virch.  Arch.,  129  Bd.,  1892. 
Nagel:  Entwickelungsfehler  weibl.  Genitalien.     Handb.  d.  Gyn.,  i.,  1897. 
Neugebauer:  Beobacht.  a.  d.  Gebiete  des  Scheinzwittertums.    Leipzig,  1904  (Lit.). 
Nonne:  P.seudohermaphrodismus  mascul.     Jahrb.  d.  Hamb.  Kraukeuanst.,  ii.,   Leip- 
zig, 1893. 
Obolonsky:   Zur  pathol.  Anat.  d.  Hermaphrodi.smus  homiuis.     Zeitschr.  f.  Heilk.,  ix., 

188S. 
Piitz;  Hermaphrodismus  verus  unilateralis  b.  Schweinc.     Deut.  Zeitschr.  f.  Thiermed., 

x\.,  1889. 
Raake:  Hermaphrodi.smus  spur.  masc.  int.     Wlirzburger  Verb.,  1890.  (Lit.). 
Salen:  Hermaphrodismus  verus  unilateralis.     Verb.  d.  Deut.  path.   Ges.,  ii.,  Berlin, 

I'.IOO. 
Schmorl:  Ein  Fall  von  Hermaphrodismus.     Virch.  Arch.,  113  Bd.,  1888. 
Siegenbeek  van  Heukelom:  Tubuliirer  und  glandularer  Hermaphrodismus.     Beitr. 

V.  Ziegl.r,  xxiii.,  1898. 
Simon:  Hermaphrodismus  verus.     Vireli.  Arch.,  172  Bd.,  1903  (Lit.). 
Stroebe:   Pseudf>herniaphrodisnius  masc.  int.     licit r.  v.  Ziegler,  xxii.,  1897. 
Taruffi:   L'Ennafrodismo.     Mem.  della  Ace.  delle  Sc.  dell'  Isi.  di  Bologna,  1899  (Lit.); 

Jlcrniaiiiinuiismus  u.  Zeugungsfahigkeit.     Berlin,  1902(Lit.) 
Virchow:  Wiuzburger  Verb.  IIL     Berl.   klin.   Woch.,   1872;  Ges.  ATih  ,  Frankfurt, 

18:)0. 

Wermann:  P.seudoliermaphrodismus  masculinus  completus.  Yirch.  Arch.,  104  Bd., 
1880. 

Winkler:  Pseudohermaplirodismus  masculinus  internus.     Inaug.  Diss.,  Zurich,  1893. 

Zweifel:  Krankh.  d.  auss.  weibl.  Genitalieu.  Hanbd.  d.  Fraueukraukh.,  iii.,  Stutt- 
gart, 1886. 

5.  Double  Monsters. 

(a)   C/as.sification  of  Double  Mon.sfers. 

§  144.  Twin=foriTiations  lyingwitliiii  iisini;!*'  choi-ion  may  hr  divided 
into  two  large  groups:  twins  comphiebj  nrparatrd  front  onr  anoflirr,  and 
tu-iuH  united  by  some  po)tion  of  their  bodies. 

Of  the  twins  completely  separated  from  one  another  Ihcre  may  he 
(U.stinguished  two  tyjies;  one  \n  which  bof/i  tn-in-s  ((re  ful/i/  drrrbtprd,  and 
one  in  which  one  tn-in  is  shnilcd. 

Twins  joined  togethier  by  portions  of  their  bodies  may  likewise  be 
also  divided  into  two  groui)s:  tn-ins  showinn  uniform  development  and  twins 


540 


DISTURBANCES  OF  DEVELOPMENT. 


shoiri)i(/  an  niuqmd  development.     To  the  latter  belongs  an  especial  group 
of  greatly  stunted  parasitic  forms  that  may  be  classed  as  teratomata. 

According  to  the  situation  of  the  duplicated  portions  of  the  body, 
there  may  be  distinuished  (Foerster)  : 

1.  Monstra  duplicia  katadidyma  or  duplicitas  anterior. 

2.  ]\r<tns1ia  dui)licia  anadidyma  or  duplicitas  posterior. 

3.  Monstra  duplicia  anakatadidyma  or  dujilicitas  parallela. 

In  general,  these  may  also  be  con 
veniently  divided  into   three   classes  i 
(Tarufifi)  : 

1.  Twins    united    chiefly   by   the 
epigastrium  and  thorax. 

'1.  Twins    united    chiefly   by   the 
heads. 

o.  Twins    united    chiefly   by   the 
pelves. 


Fig.  no.— Acarrii'.is  acephalus,  showing  a  riidinientarv  development  of  the  lower  extremities  (aeanlius 
amorphus). 


Fig.  411.— .\eardius  pseudoaconnus.     (.\fter  Barkow.)     a,  Ht 
treniity;  c,  rudimentary  intestine  ;  d,  artery;  r,  vein. 


h,  nuiiuieut  of  the  left  upper  ex- 


Ahlfeld  divides  the  double  monsters  into  two  chief  groups,  those  with 
romplete  and  iUoae  icith  paHial  doubling  of  the  axial  structures. 
In  very  rare  instances  triple  monsters  occur. 

Literature. 

(Double  Monsters.) 

Ahlfeld:  Die  Missbilduniren  des  Monschcn,  Leipzig,  1880,  1883. 

Foerster:  Ww  ^Nlis'^bilchinircn  des  Mensclicn,  Jena,  18G5. 

Marchand:  :\nssl)ildun,u:cii.     Eiilenburir's  Realencyklopiidic,  xv.,  1897. 

Taruffi:  Sii'.r  ordiiiarneiito  dclla  teratologia.     Mem.  della  R.  Ace.  delle  Scienze  dell' i 

Istitiito  di  IJologiiii,  v.,  180G;   vii.,  1898. 

See  also  ^  131. 

(/>)  The  (lilef  Forms  af  Double  Monsters. 
g  145.  Twins  separated  from  each  other  and  lying  within  a  single 
chorion  are  designated  homologous  twins.     They  are  always  of  the  same 


DOl  BLE    MONSTERS.  541 

sex,  have  usually  a  commou  placenta,  ami  resemble  each  other  very 
closely.  If  from  any  cause  one  of  llie  twins  shonld  die  after  its  body  has 
l>eeu  developed,  it  may  be  pressed  tlat  by  the  continned  growth  of  its 
fellow.  y,ivini;-  rise  to  the  condition  known  as  foetus  papyraceus. 

When  twins  possess  a  commou  placenta  witliiii  which  the  lih>od- 
vessels  have  abnndant  anastomoses,  the  heart  of  tlie  stijujier  Icelus 
may  eonti-ol  the  circulatiou  and  thereby  cause  chauj>es  in  the  direction  of 
the  blood-stream  in  the  weaker  twin.  As  !>•  ivsnlt  of  tliis  the  latter  snf- 
fers  severe  distnrbances  of  development,  and  become;;  clianjie<l  into  an 
acardius,  a  mon.sfcr  without  a  heart,  (nther  develo]un«;-  uo  heart  at  all  oi- 
only  a  rudimentary  one.  \n  the  maj(U'ity  of  such  cases  t  lie  hf(i<l  also  /'ni/.s 
to  develop  {(leordiKS  aeephah(.s)  or  ivmains  rud'aneittdnj  (aedi-diK.s  panicrjih- 
aliis),  and  likewise  there  is  usually  no  development,  or  only  a  rudimen- 
tary one,  of  the  upper  extremities,  thorax  Malls,  luni;s,  aud  liver,  while 
the  abdomeu,  pelvis,  and  lower  extremities  are  more  or  less  perfectly 
formed  (Fig.  410).  Accordiug-  to  the  development  of  the  extremities 
the  followiug  varieties  maj^  be  distinguished:  aeardius  XHimcepalns  [or 
acephaJus)  symjiiis,  monojms,  dipiis,  )nonobr((rhius,  dihraehiKfi. 

lu  rarer  cases  there  is  uo  recognizable  development  of  auy  part  of  the 
body,  aud  there  is  formed  an  aeardius  amoiphn.s,  consisting  of  a  shai)eless 
mass  covered  with  skin,  usually  without  any  indications  of  extremities, 
and  possessing  iuterually  ouly  rudimeuts  of  organs. 

Of  very  rare  occurrence  is  the  formation  known  as  an  aeardius  pseu- 
doaeorm us  (Fig.  411) — that  is,  a  monster  in  which  the  head  (^0  ou\\  is  de- 
veloped, wliile  the  other  parts  of  the  body  are  represented  only  by  small 
rudiments  (/>,  e). 

Literature. 

(Acardius. ) 

Barkow:  Pseudoacormus,  Breslau,  1854. 

Claudius  •  Die  Eutwickelung  der  lierzlosen  Missgeburten,  Kiel,  1859. 

Dareste-  Compt.  reut.  de  I'Acad.  des  sciences,  1865,  1873. 

Heller:  Acaidiacus  amoipluis.     Virch.  Arch.,  129  Bd.,  1890. 

Hirschbrucli :   Das  Problem  der  lierzlosen  Missgeburten.     Inaug.  Diss,  Berlin,  1895. 

Lowy:  Acardiaciis  anceps.     Prag.  med.  Woch.,  1892. 

Mvilder:  Ueber  eine  lierzlose  Missgeburt.     Inaug.-Diss.,  Freiburg.  1891. 

Orth:  Drei  menscbl.  Missgeburten.     Virch.  Arcli.,  54  Bd..  1872. 

Panum:  Zur  Keuntn.  d.  phys.  Bedeutung  d.   angeb.    Missbihhnigeu.     Vinli.    Arch., 

72  15d.,  1878. 
Perls-  Lehrb.  d.  allgem.  Pathologic,  ii.,  Stuttgart,  1879,  1886. 

See  ai.so  §  147. 

§  146.  Twins  equally  developed  and  united  to  each  other  occur  in 
the  following  principal  types: 

1.  Duplicitas  anterior  (monstra  duplicia  l-atadidj/ma).  Anteiioi-  du- 
plication with  union  of  posterioi  portions  of  the  body. 

Pygopagus  (Fig.  412).  Union  of  the  twins  in  the  region  t»f  the 
coccyx  or  of  the  sacrum.  According  as  the  union  is  mcnc  oi-  le.^s  exten- 
sive, the  sacrum,  coccyx,  lower  end  of  the  medullary  canal,  anus,  lower 
end  of  the  bowel,  and  the  sexual  apparatus  are  either  doui»led  or  aie  in 
part  single. 

Ischiopagus  (Fig.  413).  Union  of  the  twins  in  the  pehi.s  which 
thereby  forms  a  wide  ring,  the  two  sacia  being  i>laced  ojiposite  each 
other.  The  anus,  lower  end  of  the  bowel,  and  tiie  sexual  organs  may  he 
single  or  double,  and  the  nnnd)er  of  the  lower  extremiliev;  iw..  to  four. 


542 


DISTURBANCES  OF  DEVELOPMENT. 


Dicephalus  (Fi^-.  414)  and  diprosopus  (Fig.  415).  The  duplication 
is  liinilcd  to  the  upper  pait  of  tlie  trunk  and  bead,  or  only  to  the  neck 
and  head,  or  the  head  alone,  or,  finally,  only  to  portions  of  the  head. 
As  the  external  blending  increases  in  extent,  there  occurs  also  a  blending 


Fig.  n-Z. 


Fig.  413. 


Fig. 
blenrlcii 
verti-bra 
miiiiitc  i 

Fig. 


-Pvsropa<,nis.  (After  Marchand.)  A,  B,  The  two  twins;  a,  b,  separated  umbilical  cords;  c, 
licalCords;  c?,  ccmmon  placenta.  There  is  a  single  coccyx  and  sacrum  (from  the  second 
iwaid),  and  the  lower  end  of  the  medullary  canal  is  single.  The  two  intestinal  canals  ter- 
aiial  opening.  Vestibule  of  vagina  single,  the  remaining  portions  of  the  sexual  organs  double. 
-Ischiopagus.    (After  Levy.) 


of  the  internal  organs,  the  intestine,  liver,  lungs,  heart,  spinal  cord, 
brain,  etc.  According  to  the  number  of  the  lower  and  upper  extremi- 
ties there  may  be  distinguished  dicephaJm  tetrapus,  dipus,  tftrahracMus, 
tribrachin.H  dihrachhis  fFig.  414).  When  tlu'  lieads  luive  blended  there 
may  be  (list  inguished  dipvoHopus  Mropldludmns,  triopJdh(d))ii(s,  diopIdlndmHK, 
tftrotus,  triotiis,  diotiis,  distomufi,  monodomm,  tribrachim  and  dibradtius  (Fig. 
415). 

The  mildest  grades  of  duplicitas  anterior  are  represented  by  the  rare 
cases  of  ilKjdicdiion  ofthcjair,  mouth,  or  nose. 

2.  Duplicitas  posterior  (monstra  dupUcia  anadidyma).  Union  of  the 
twins  at  the  head  and  tlience  fartlier  downward  witli  duplication  of  the 
posterior  parts  of  tlie  body. 

Craniopag's  (Fig.  416).  ITnion  of  the  twins  in  the  cranial  region. 
Accoidiiig  to  tlie  site  of  union  there  may  be  distinguished  craniopar/us 
pdriiltilis,  j'r<iiil(i/i.s,  ix-cipitidis.  When  the  union  is  more  extensive  por- 
tions of  the  biaiii  are  also  single. 

Cephalothoracopagus  or  syncephalus  (Fig.  417).     Blending  of  the 


DOUBLE    MONSTERS. 


54;{ 


twins  ill  the  region  of  the  forelieiul  and  face,  and  in  ])ai-t  also  of  \\\r 
abdomen.  In  the  region  of  the  united  lieads  tlieie  is  an  anterior  and  a 
posterior  face  (jaiuts,  janiceps).  Tlie  two  faces  maybe  equally  (Jaiiufi 
si/iiimetros)  or  unequally  developed  (janiis  (Lsi/mmctroN),  one  face  i)cing 
well  developed,  the  other  imperfectly.  The  inteinal  organs  present  dif- 
ferent degrees  of  blending  and  union  into  single  organs. 

Dipygus.  The  duplication  is  limited  to  the  lower  lialf  of  the  body 
and  the  lower  extremities,  while  the  upi)er  i)arts  are  eithei-  wholly  single 
()!•  only  iiartly  cleft.  The  duplication  of  the  spinal  cord  may  begin  at 
different   heights.     According  to  the  number  of   extremities  dilfeicnt 


Fig.  411. — Dicephalus  dibrachius  tlipus. 


Fig.  41.").— I<ipr().s(jpiis  distoiiuis  tetroplithalnius  dlo- 
tiis  dibrachius. 


forms  may  be  distinguished.  The  mildest  grades  of  diiplicat  ion  are  con- 
fined to  the  lower  end  of  the  spinal  column,  the  anus,  and  the  external 
genitals. 

3.  Duplicitas  parallela  (monstra  dnpUcia  anahatadidi/iiia  ).  Duplica- 
tion of  theanterior  andi)osterior  ends  of  the  body  with  parallel  positions 
of  the  tiunk. 

Thoracopagus  (Fig.  418).     Union  of  the  twins  by  tiie  thorax.     Ac- 
^'  ^  it  of  the  union,  as  well  as  the  nnnd)er  of  ex- 

tremities present,  there  may  be  distinguished  different  forms,  i)articularly 


I CT V--!-|- '- 

cording  to  the  site  and  extent  of  the  union,  as 

jmities  present,  there  may  be  distinguished  d. ,  ^ 

the  following:  xi2)hopaf/u>i\mnou  at    the  xiphoid  process),   nfmioiKif/us 

(union  at  the  vSternum  j,  thoraropaf/us  tffrohrachius,  trihrorliiKs,  dihrnr/iiiis, 

^    "  When  portions  of  the  faces  liave  blended 


ietrapus,  tripun,  and  dipus. 


544 


DISTURBANCES  OF  DEVELOPMENT. 


there  results  a  prompotlwmeopagus.     Blending  and  union  of  tlie  internal 
oro-ans  into  sin.u:le  organs  vary  with  the  degree  of  external  blending.     The 
heart  may  be  double  or  single,  in  the  latter  case 
malformed.       Thoracopagus    is    relatively   fre- 
quent. 

Rachipagus.     Blending  of  the  twins  in  the 
region  of  tlie  spinal  column  is  very  rare. 

Literature. 

{Double  Monsters.) 

Ahlfeld:  Die  Missbilduugeu  des  Mensclien.  Leipzig,  1880. 

Barkow:  JMonstra  animalium  duplicia  per  auatumen  la- 
da  uata.  Lipsise,  1828. 

Burckhard:  Zwei  Doppelmissbilduugen.  Zeit  f.  Gebh., 
xl.,   1S98. 


fM- '',  I 


Fic.  416.  FiG.-iir. 

Fig.  416.— (Taiiiopagus  parietalis. 

Fig.  417.— Ccphalotlioracopagus  or  svncephalus,  with  janus  head.    Both  anteriorand  posterior  faces 
malformed,  and  possess  but  one  eye,  while  the  nose  is  represented  by  a  proboscis-like  organ  situated  above 
the  eye. 

Henneberg:  Vcrlialten  d.  Pygopagen  Rosa  u.  Josefa.     Berl.  kliu.  Wocli.,  1903. 

Kamann:  Thoracopagus  tetrabrachius.     A.  f.  Gyn..  68  Bd.,  190iJ. 

Lochte:   Dopixliaissbildiingeii.    Beitr.  v.  Ziegler.  xvi.,  1894. 

Marchand:  Pvirojiagus.     Beitr.    v.    Ziegler,    xvii.,     1895;    Missbilduugeu.    Eulenb, 

i{cal.-ii(yl<l<ip.,  l's9:. 
Martinotti  e  Sperino:  Diprosopus  tetrophthalmus.    Internat.  Monatsschr.  f.  An.,  v., 

1888. 


DOLBJJO    MONSTERS. 


545 


Riihe:  Janiot'iis  asymniotros.     Inaug.-Diss.,  ^NrarbuiLr,  IS!)."). 

—  Schaefer:  l'el)cr  I'iiicn  Diceplialus.     Bt'itr.  v.  Zit'irlcr,  xxvii.,  liKMi. 
Sieg-enbeek  van  Heukelom:  Moustr.  clouhlc.    "l{(c.  dc  tniv.  dii  I,ah.  Boerlmave,  i 

|S9!). 
Taruffi:  Synci'iihalus  dilccamis  (Venloiip  v.  Penis.  Scnilimi.    AiiusK     ^Meni.  1{.  Ace. 
r.olouna.  ix.,  ISSII;  Fcto  iiiuano  con  due  niandiliolc.      II..,  ii.,  IS!).-,. 

—  Virchow:  Pviioiiaiius.     licii.  klin.  Woeli.,  1S7:!. 

See  also  s;^  131  and  147. 

^  147.  Twins  joined  together  but  unequally  developed  may  occur 
in  any  of  the  donblc  fornis  desciilu'd  in  ^  14().  If  the  dovch»i)nicnl  of 
one  of  the  twin.s  reniain.s  i-udiinentai-y  and  if  its  heart  does  not  deveh>j). 
its  noni'ishment  can  come  only  throuuh  its  Mell-d«'\('h)i)ed  fcUow.  The 
better  developed  of  Ihe  t^o  is  then  known  as  tiic  autosite,  the  otlicr  as 
the  parasite.  If  tlie  parasite  is  of  only  very  rndinientary  development, 
it  may  be  classed  with  the  bigerminal  teratomata  (cf,  J^J^  H>7  and  1:28). 


Fig.  418.— Tboracopafc 
posses.se.s  two  doi-sal  surfaci 
third  foot  has  eight  toes. 


<  tiil)ra<-liius  tri|ius       Hit  liiiidof  iIk    tliiid  a 
and  ttie  hiterallN  distmted  ilnp  i>,  possess  nails 


At  the  post rri or  rnds  of  fhr  hod// thi^ro  may  occur  a  rudimentary  donl)le 
iimiistiosity  in  the  form  of  an  inrrcasr  in  the  niiiuhfr  of'  llir  r.tironitiiK,  <i 
1)1)1// in <l OH  (Figs.  419,  420).  In  so  far  as  th<'  lowei-  extivmilies  aic  con- 
cerned such  a  malformation  may  be  clas,sed  as  an  ischioi)agus  or  a  <lipy 
gus.  The  supernumerary  exti-emities  may  be  one  or  two  in  nuiiibei-,  and 
more  or  less  M^ell  developed.  Fuithei-,  there  not  infiecpiently  occur 
cocr/iymJ  terato}ii(ita  in  which  the  piesence  of  rudimentary  exti-emities 
(Fij;.  421,  a,  />,  c)  or  of  various  body  eh'inents  leaves  no  doubt  that  llie 
tiiiMor-like  formation  covered  by  the  skin  of  the  autosite  is  to  be  regarded 
So 


546 


DISTURBANCES  OF  DEVELOPMENT. 


as  a  double  monster,  a  rudimentary  pygopagus,  or  else  as  dipygits  parasiticus. 
Such  a  parasite  is  designated  as  an  epipygus. 

Supernumerary  extremities  (Fig.   422)   may  also  be  found    upon  the 


Fig.  419.— Polymelos.     (After  Lancf  reaux.) 


Fig.  420.-Polymelos.    (After  Liesehing.; 


Fk;.  421 


Fig.  421.— Bipentiinal  tHratoma  of  tbe  coccygeal  region  (pygopagus  parasiticus),    a,  b,  c,  Extremitif 
lying  In  a  mk-  formfd  liy  ihc  skin  of  the  autosite. 

Fii;.  4~.-'l'linni(ii|)aL'-us  parasiticus  (thoracomelus).    Three  legs  spring  from  the  pelvis;  one  of  the 
lias  a  double  loot.    Two  upper  extremities  project  from  the  anterior  chest-wall. 


Fig.  422, 


DOUBLE    AIOXSTERS. 


547 


trunk,  ov  flicrc  nun/  occur  a  lic(((JJ(:ss  innik  irilli  c.iircuiific.s  (V'l'^.  IL'.")),  or  ;i. 
rudintciitiOj/  thorax  iril/ioid  c.rtrcriiHic.s,  or,  liiially,  tcr<ilonial(i  wliicli  iii;u'  he 
interpreted  as  tJioracojxtf/Ks  )><t)-((.sitici(s  {otiiplidlopof/Hx)  and  as  (lipi/r/us  jxini- 
sitiru.s.     Tlie  nialtorniation  is  also  often  called  cj)i(/((striu.s. 

The  inclusion  of  such  teiatomata  beneath  the  skin  of  the  abdomen 
or  thorax,  or  within  the  abdominal  or  thoracic  cavities  of  the  autosilc. 
gives  rise  to  the  condition  known  as  inelu.sio  faiaJis  suhcuta)ic<t,  or  dhi/om- 
inalis,  or  mediastinal  is.  The  abdomiual  inclusiou  is  also  designated 
cn(/astrii(S. 


FiG.4'^3.— TlioracopaRus  parasiticus.    (After  Schenk  von  GrafenberR.)    Parasite  attached  to  chest  of 
(    autosite. 

Fig.  424.— Epignathiis.     (After  Lancereaux.) 

In  the  region  of  the  head  rudimentary  twin-formations  ai)i)ear  most 
often  in  the  mouth  cavity,  forming  usually  an  amorphous  mass,  lii-mly 
I  attached  to  the  base  of  the  skull,  and  consisting  of  skin,  connect i\e  tis- 
1  sue,  cartilage,  bone,  brain-tissue,  teeth,  intestinal  elements  and  muscle, 
I  and  rarely  developed  extremities.  Such  malformations  are  included 
!  under  the  designation  of  cpif/nathns  (Fig.  424). 
j        On  other  parts  of  the  head  {prosopopafins  para.sHicns)  Tudimentaiy  t  win 


formations  oi-  bigerminal  teratomata  aic  very  lare  (cf, 
they  occur  also  in  the  ci-anial  cavitv  (cncranins)  and  in 
colU). 

Literature. 

(IJnequal  Double  Monsters.) 


^^  11*7,  IL'S);    but, 
the  Jieck  (hi/f/ronia 


Bohm:  Saoralteriitom.     Px 
Braune:  Die  Doiipclljildu 

1S(;2. 
Breslau  u.  Rindfleisch. :  Foetus  in  foeti 
Calbet:  ("ontiib.  A,  I'et.  des  tuineiirs  coi 

(■o((\  Lcienne,  Paris,  1893. 
Foederl:  Dipygus  parasiticus.     Langeiibeck's  Arch. 


klin.  Wocli.,  1872. 

n   u.  angel).   Gesclnvulste  d.  Kreuzbeingcgciwl.  Leipzig, 

Virch.  Arch.,  30  Bd..  1S(;4. 
en.  d'origine  parasilaire  de  la  region  sjicro- 

18  Hd.,  1S09. 


548         "  DISTURBANCES    OF    DEVELOPMENT. 

Freyer:  Kieuzbeingeschwulst.     Vircli.  Arch.,  58  Bd.,  1873. 

Gross:  Les  monstres  doubles  parasitaires,  Nancj',  1877. 

Hennig:  Congeiiitale  echte  Sacraltiimoren.     Beitr.  v.  Ziegler,  xxviii.,  1900. 

Israel:  Ein  Fall  von  Verdoppelung  der  1.  TJnterkieferluilfte.     Inaug.-Diss.,  Berlin, 

1867. 
Moussaud:  Dcs  inclusions  foetales.     These  de  Paris.  1861. 

Otto:  ZusaninK'nstellung  d.  bestbeschrieb.  Falle  v.  Epignathus.  Arch.  f.  Gyn.,  viii. 
Schwalbe:  Der  Eiiignathus.  Beitr.  v.  Ziegler,  xxxvi.,  1904. 
Schwarz:  Bcitr.  /,.  Gcschichte  d.  Foetus  in  foetu,  Marburg,  1860. 
Taruffi:  Caso  d'cngastro  aniorfo  extraperitoneale.  ]\Iem.  K.  Ace.  Bologna,  iii.,  1893. 
Wright  and  Wylie:  Included  Fa-tus.  Brit,  Med.  Journ.,  ii.,  1900. 
See  also  i^J^  127,  128,  131,  144,  and  146. 


CHAPTER  X. 

The  Pathogenic  Fission-fungi  and  the  Diseases  Caused 
by  Them. 

I.     General  Considerations  Regarding  the  Schizomycetes  or  Fission- 
fungi. 

1.  General  Morphology  and  Biology  of  the  Fission-fungi. 

§  148.  The  Schizomycetes  or  fission=fungi,  often  also  designated 
collectively  as  bacteria,  belong-  to  the  j>/v>/o^>//?/^'.s— that  is,  to  the  smallest 
simplest  forms  of  plant-life.  Many  of  them  are  so  small  that  they  stand 
upon  the  very  border-line  of  invisibility  even  with  the  nseof  the  highest- 
power  objectives  and  eye-pieces.  When  ocenrring  in  animal  tissnes,  it 
is  often  very  difficult  to  distingnish  them  from  the  products  of  cell-dis- 
iutegration ;  and  often  this  can  be  accomplished  only  through  the  em- 
ployment of  specific  reagents  or  staining-methods,  and  occasionally  only 
through  culture  experiments. 

The  Schizomycetes  throughout  are  iton-chJorophi/llaceous,  nnicelluhir  or- 
ganisms, but  as  a  result  of  their  growth  and  multiplication  they  often 
form  colonies  made  up  of  numerous  cells. 

The  form  and  character  of  the  single  cells,  as  well  as  Ihcir  maiiiicr  of 
growth,  division,  and  multiplication,  vary  greatly,  and  at  i)resent  tlu-se 
differences  are  used  as  a  basis  for  the  classification  of  bacteria.  lu  the 
first  class  are  placed  the  Cocci,  often  designated  as  Micrococci  oi-  as  Sjtluvro- 
bacteria  (Colin),  that  form  of  bacteria  which  constantly  occurs  iu  the 
form  of  spherical  or  ovol  cells.  According  to  the  grouping  of  the  cells 
during  their  division,  there  maybe  distinguished  six  forms  of  cocci: 
double-cocci  or  Diplococci,  chain-cocci  or  Streptococci,  clustered  cocci  or  Staph- 
ylococci, tablet-cocci  or  Merismopedia,  packet-shaped  cocci  or  SarcitHV,  and 
tube-cocci  or  Ascococci. 

The  second  class  constitutes  the  Bacilli  (lod-shaped  l)actcria)  which 
formerly  were  divided  by  Colin  into  Microhactcria  and  Ihsmohaclrria,  ac- 
cording to  the  length  of  the  rods.  These  may  also  be  (h-signatcd  as  short 
rods  and  lonr/  rods.  In  association  with  the  designation  hacil/n.s  many 
authors  use  the  term  Clostridium,  ]»articulaily  for  bacilli  which  during 
spore-formation  assume  spindle  or  club  shapes.  L(»iig  threads  art-  often 
also  called  Leptothrix. 

To  the  third  class  belong  the  Spirilla  (screw-shaped  bacteria). 
Screw-shaped  forms  with  short,  wide  turns  are  known  as  Spirilla,  those 
withdrawn-out  turns  as  Vibrios,  those  with  a  long,  clos<'l>  wound  sciew  as 
Spirochetes.  According  to  their  length  tlie  spirilla  may  also  be  di\  id.d 
into  sho}i  screus  and  lonf/  screws. 

All  of  the  bacteria  tiius  fai-  referred  to  occur  either  iu  one  singh-form 
or  in  a  very  limited  cycle  of  forms  of  growth,  and  they  may  theiefore  be 
grouped  together  as  monomorphous  or  oligomorphous  bacteria.     (  oliu, 

549 


550  THE    PATHOGENIC    FISSIOX-FUXGI. 

to  whom  we  are  indebted  for  the  fimdauieutal  iuvestigatious  regard-l 
ing  bacteria,  united  under  the  term  bacteria  only  the  oligomorphic 
forms. 

:Many  writers,  however,  classify  also  as  bacteria  those  organisms  which 
during  their  development  pass  through  a  whole  series  of  forms:  spherical 
cells,  as  well  as  rods  and  simple  and  branching  threads.  These  may  be 
collected  into  a  second  group— the  polymorphous  bacteria— to  which 
belong  in  particular  the  fungi  known  as  ^treptothiix,  Ciadothrix.  Beg- 
f/iatoa,  Cirtiothri.r,  and  Actinomyces.  Other  authors  (Lehmann,  ^en- 
niann,  Levy,  Lubarsch)  class  these  forms  with  the  HypJw)n>/crff's  or  regard 
them  as  transition  forms  between  the  latter  and  the  Schizomi/cetes.  Pe- 
truschki  collects  them  under  the  family  term  of  hair -fun  [/us  or  Trichomy 
cetes,  and  classes  them  with  the  Eyphomycetes. 

All  of  the  Schizomycetes  consist  of  a  plasmatic  cell=contents  and  a 
cen=membrane,  l)oth  of  which,  according  to  Xencki,  consist  essentially 
of  an  albuminoid  body,  mycoprotein,  which  varies  with  the  species. 
Manv  bacilli  contain  fat  within  their  cell-bodies,  at  times  so  abundantly 
that  it  may  be  demonstrated  by  staining  with  Sudan  III,  Some  of  these 
bacteria  (tubercle -bacillus,  lepra-bacillus,  and  actinomyces)  show  the 
presence  of  fat  both  when  growing  in  living  tissues  and  when  cultivated 
upon  artificial  media;  others  (staphylococcus  aureus,  anthrax-bacillus, 
bacillus  of  glanders)  show  the  presence  of  fat  only  when  grown  upon  cer- 
tain media  (Sata).  In  many  forms  of  bacteria  the  membrane  under  cer- 
tain conditions  may  swell  and  appear  as  a  hyaline  capsule  surrounding 
the  bacterial  cell.  . 

In  all  forms  of  bacteria,  with  tlie  exception  of  the  cocci,  there  havt 
been  observed  swarming  movements  which  are  brought  about  by  mean; 
of  fine  thread-like  flagella  attached  singly  at  the  ends  or  scattered  ove 
the  entire  bacterial  cell.  In  addition  there  also  occur  slow  oscillaton 
or  gliding  and  creeping  movements  which  are  dependent  upon  the  con 
tiactile  and  flexible  qualities  of  the  plasma.  Both  forms  of  motion  occu 
only  under  certain  conditions  of  nutrition  and  growth,  and  only  in  cer 
tain  species. 

Hultiplication  of  bacteria  takes  place  through  a  transverse  divisioi 
of  cells  which  have  previously  become  elongated.  In  some  forms  divi 
sion  can  also  take  place  in  two  or  even  three  dimensions.  After  divisioi 
th«'  cells  separate  immediately  or  remain  for  a  time  attached  to  eacl 
other.  When  the  cells  remain  attached  after  dividing  transversely 
threads  are  formed  {Streptococcus,  Leptothrix)  ;  after  dividing  both  trans 
veisely  and  longitudinally,  flat,  tablet=Iike  colonies  (Mcrismopcdia) 
after  dividing  in  all  three  dimensions,  colonies  resembling  a  solid  bod:; 
{Sarcina)  are  produced.  Long  threads  may  become  segmented  iut<! 
shorter  pieces. 

According  to  the  investigations  of  Buchner,  Longard,  andEiedlin,  th«j 
period  of  ]ei)roduction— that  is,  the  time  from  one  cell-division  to  tb, 
next- is,  ill  tlie  case  of  the  cholera-spirilhmi  under  favorable  conditionj 
of  initrition,  about  fifteen  to  forty  minutes. 

if  i-esting  bacterial  cells,  as  the  result  of  a  constantly  progressing  re 
production  or  through  the  accumulation  of  neighboring  cells,  heap  them 
selves  anywhere  in  great  masses,  there  are  often  formed  jelly-like  colo 
nies,  which  are  called  zobgloea.  The  jelly-like  substance  is  formed  frorj 
the  membranes  of  the  bacteria  and,  according  to  Xencki,  consists  o; 
mycoprotein.  The  j«'lly  masses  may  assume  the  most  varied  form,  ami 
occasionally  reach  a  large  size,  so  that  the  clumps,  or  lobulated  masses 
or  strands  mav  attain  a  diameter  of  one  to  three  or  more  centimetres. 


GENP:KAL    MOHIMIOLOGY    AM)    HIOI.OCV.  o")! 

1  iuUt  certain  (■(•iiditioiis  many  (if  the  l)a<-t('ria  ftuin  spores.  'I'hi^c 
are  cells  Miiicli  are  distin<iiiislu'(l  by  the  I'act  tliafrllicy  icniaiii  alixc  nndcr 
conditions  in  Miiicli  the  ordinary  forms  of  ve.u'etation  die;  and,  m  lieu 
brought  into  fresh  nutrient  solutions,  are  abl(^  to  i)roduce  :i  new  gener- 
ation. Spo-e-t'orm((ti())i  is  most  fivquenlly  c^//7o</c»o/rs' — tliatis,  the  .si)oi'e 
arises  inside  the  cells  (particuhuiy  iu  bacilli),  and  is  developed  out  of 
the  cell-protoplasm,  iu  which  there  appears  a  small  granuh^  which  grows 
into  an  oblong  or  round,  highly  refiaclive,  sharply-contoured  Ixxly 
always  remaining  smalh^r  than  tlu^  mother-cell.  After  the  death  of  the 
latter  the  spore  is  set  free.  Artlifogcuoii.s  spofc-fotiiidtioii,  asobser\(Ml  in 
inici-ococci,  is  said  to  occnr  through  the  direct  assumption  of  s])ore-(|uali- 
ties  by  individual  members  of  a  colony  or  of  a  series  of  gcneritions,  Mhicli 
at  the  same  time  remain  externally  nnaltered  or  take  on  oilier  moipho- 
logical  peculiarities. 

Iu  old  cultures  bacteria  nearly  always  show  degeneration=forms, 
which  are  swollen  and  distorted,  and  stain  poorly  and  iricgulaily. 

As  non-chlorophyllaceons  plants,  the  schi/.omyceles  are  restiicted  iu 
their  nutrition  entirely  to  ready-formed  organic  substances  which  are 
soluble  in  water,  and  which  are  also  su[)j)lit'd  to  them  iu  an  abundance 
of  water.  In  addition  they  need  also  various  mineral  substances, 
especially  sulphur,  phosphorus,  iDotassium  or  rubidium,  or  ca'sium  and 
calcium  (or  magnesium,  barium,  or  strontium).  Changes  in  the  condi- 
tions of  nutrition  may  modify  the  form  and  dimension  of  bacteria  and 
Eilso  change  their  vital  properties. 

Some  of  the  fission-fungi  are  either  chiefly  or  m holly  lest rid ed  I'ni- 
their  food-supply  to  dead  organisms  or  to  solutions  of  organic  matter, 
and  are,  therefore,  classed  as  saprophytes  ;  otheis  are  able  to  take  Iheir 
uutritiou  also  from  living  animals  or  i)lants,  and  live  as  parasites. 

If  bacteria  get  into  water  which  contains  uo  food-mateiial,  many  of 
them  die  in  time.     The  spores  survive  the  longest. 

Free  oxygen  is  necessary  for  the  development  of  many  bacteria; 
others  can  dispense  with  it  as  long  as  they  are  under  favoral)le  conditions 
of  nutrition  in  other  respects;  others  develop  only  in  the  absence  of  oxy- 
gen. The  first  are  designated  obligate  aerobes,  the  second  faciiKatlre 
anaerobes,  the  third  obligate  anaerobes. 

The  ])athogenic  bacteria  are,  accoiding  lo  Lil)oiius,  racnl(ali\-e  or 
obligate  anaerobes. 

Carbon  dioxide  has  no  influence  ui)on  the  dt'velopment  of  many 
bacteria,  as,  for  example,  upon  the  typhoid-bacillus  and  Fiiedlander's 
pneumobacillus.  Upon  others,  on  the  contiary,  it  lias  an  iuhil)i1ory 
action,  as,  for  example,  upon  Bacillus  imlleus,  Proteus  vulfiarls,  Jlaeillus 
2)hosphorescens,  the  bacilli  of  anthrax  and  cholera,  the  ])Us-cocci,  and 
others  (C.  Fi'ankel).  The  bacilli  of  anthrax,  Asiatic  ciioleia,  and  of 
rabbit  sepficiemia  die  out  in  a  few  hours  in  aililicial  Seltzer  water,  but 
anthrax-spores  remain  alive  iu  it  indefinitely  ( Ilochstetter). 

Intense  light  has  an  injui-ious  oi-  desti-uctive  inlluence  u])on  liie  de- 
velopment of  many  forms  of  bacteiia,  and  it  is  therefore  possible  to  dis- 
infect by  means  of  strong  light  water  which  is  infected  (Jiuchner  i.  The 
virulence  of  the  bacillus  of  anthrax  may  be  lessened  by  exjxtsure  to  sun- 
light (Arnold,  Gaillard).  AVhen  exposed  to  the  direct  rays  of  the  sun 
anthrax  bacilli  die  in  twenty-four  to  thiify  hours,  the  spores  survive  as 
long  as  six  to  eight  weeks  (Ai-loing,  Diu-laux).  Ac<-ording  to  (Jeisler 
the  green,  violet,  and  ultia-violet  rays  aie  ])ailicularly  active.  Accord- 
ing to  Eieder  bacteria  may  be  destroyed  by  the  IJoentgeu-rays. 


552  THE    PATHOGENIC    FISSION-FUNGI. 

Tlic  temperature  of  the  siirroniKliii,2:  medium  acts  in  general  upon  tlie 
bacteria  in  fsucli  a  way  tliat  when  it  falls  the  life-processes  of  the  organ- 
isms become  weaker  and  slower,  and  finally  cease  entirely,  whereas  with 
an  elcAation  of  the  temperature  they  rise  to  a  certain  maximum,  and  at 
a  slight  increase  above  this  suddenly  cease;  still  higher  temperatures 
kill  the  fungi.  The  maximum  of  permissible  temperature  lies  at  a  dif- 
ferent height  for  different  fungi,  and  is  in  part  dependent  also  upon  the 
character  of  the  nutrient  substance.  There  are  forms  of  bacteria  which 
grow  well  at  a  tempeiature  of  55°  C.  or  higher. 

A  low  temperature  checks  development  in  all  varieties ;  they  fall  into 
a  state  of  immobility,  but  do  not  die  even  at  great  degrees  of  cold.  The 
immobility  due  to  cold  occurs  at  different  temperatures  with  different 
varieties.  The  most  favorable  temperature  for  development  lies  between 
30°  and  40°  C.  for  the  anthrax  bacillus;  at  temperatures  above  44°  and 
below  15°  C.  its  develoj)ment  ceases.  3Iany  bacilli  form  spoi-es  only  at 
high  temperatures. 

Boiling  water  and  steam  at  100°  C.  kill  all  bacteria  and  bacterial 
spores  if  allowed  to  act  for  some  time.  In  dry  air  bacteria  and  their 
spores  withstand  higher  temperatures,  so  that  a  temperature  of  140°  C. 
for  three  hours  is  necessary  to  kill  the  latter.  Many  bacteiia  are  killed 
at  a  temperature  of  60°  to  70°  C,  provided  it  is  kept  up  for  a  very  long 
time. 

Anthrax-spores  die  in  boiling  water  in  two  hours,  in  confined  steam 
iu  ten  minutes.  The  action  of  steam  at  105°  C.  for  ten  minutes  kills  all 
spores.  Lice  .nteam  kills  all  spores  in  ten  to  fifteen  minutes,  and  i)ene- 
trates  very  well  into  the  objects  to  be  disinfected  (Koch,  Gaffky,  Lofflei'). 

If  fission-fungi  find  themselves  in  a  suitable  medium,  their  multii:)lica- 
tion  can  still  be  brought  to  a  standstill,  since  the  fluid  may  contain  sub- 
stances which  hinder  the  growth  of  the  bacteria  or  even  kill  them. 
This  effect  is  i)r(Kiuced  by  many  substances  (sublimate,  lysol,  carbolic 
acid,  iodine,  formaldehyde,  etc.) — even  in  comparatively  great  dilution. 
Other  substances  act  injuriously  upon  the  bacteria  only  when  in  stronger 
concentration.  The  point  at  which  the  multiplication  is  hindered  is 
always  reached  at  a  much  greater  dilution  than  that  at  which  tlie  bacteria 
are  killed.     Spores  are  much  more  resistant  than  the  vegetative  forms. 

The  growth  and  multiplication  of  l)acteria  also  cease  in  the  case  of 
insufficient  amount  of  water.  The  fact  that  fruits  preserved  in  sugar 
do  not  ferment  and  that  salted  and  dried  meats  do  not  putrefy  depends 
upon  this  fact.  Food -stuffs  can  also  be  preserved  through  the  lemoval 
of  water  and  by  the  addition  of  substances  which  are  dissolved  in  the 
tissue-fluids  and  in  this  way  increase  the  proportion  of  the  same  iu  solid 
contents.  The  limit  at  which  the  fission-fungi  and  yeast-fungi  cease  to 
develop  is  reached  at  a  much  higher  degree  of  humidity  than  for  the 
moulds. 

If  a  nutrient  fluid  contains  other  lower  fungi  besides  the  bacteiia 
there  often  takes  place  a  competition  between  the  different  micro-or= 
ganisms;  and  fission-fungi,  yeasts,  and  moulds  may  crowd  one  another  ji 
out.  Likewise  a  reciinocal  crowding  between  the  bacteria  themselves  J! 
may  occur.  For  example,  cocci  may  Ix' ciowded  out  and  destioyed  by  jj 
bacilli,  or  one  form  of  bacillus  by  another.  This  would  happeii  when  j| 
either  the  composition  or  the  tenii)erature  of  the  nutrient  medium  is 
more  favorable  to  one  form  than  to  the  other;  or  also  when  one  form  of 
bacteria  produces  products  -which  act  injuriously  upon  the  other,  or 
wlien  one  form  grows  more  rapidly  than  the  other,"^  and  thereby  deprives 
its  competitor  of  the  necessary  food-supply. 


GEXEKAT.    MOKlMKir.OdV    AM)    HIOLOCY.  553 

Acconiiiii;-  to  iuvt'stijiationsby  Pash'ui-,  Kmiiu'ricli,  JJoiiclianl,  W'uod- 
head,  Ijlasiovcstclionsky,  and  others,  tlic  aiiia.uoiiisiii  iM'twet'ii  many  lornis 
of  baotoria  is  shoAvn  also  in  inocnlation  «'\|n'rinu'nts  on  animals.  V,y 
simnltaiu'ons  inocnlation  Mith  dilVcicnl  hacfciia  llic  dcvi'lopmcnl  of  a 
patbogenic  bactoiinm  in  the  body  of  a  snsct'ptilde  animal  may  be  hin- 
dered. For  exani])le,  the  development  of  anthrax  bacilli  may  be  liin- 
dered  by  simnltaneons  inocnlation  uilh  eiysipelas-cocci  (Kmnieridi)  or 
with  the  Jidcilhis pi/<)(')/(i)ici(H  (IJouchard). 

The  question  as  to  whether  the  bacterial  cell  contains  a  nucleus  has  been  a  suhject 
of  much  discussion.  .4.  Fischer  denies  it.  while  Biitsclili,  Schdttclius,  Xicmann,  Zcttrmir, 
Xakanishi.inul  Feitiberg  are  inclined  to  favor  the  alfirinative  view.  .\ccor(!in<r  to  Zdt- 
7ioic,  the  bacterial  cell  contal.;s  chromatin  or  nuclear  suhstance  mixecl  with  the  eiito- 
plasm;  while  the  covering  of  the  cell,  or  ectoplasm,  does  not  contain  cliromatin.  .\ccord- 
ing  to  the  investigations  of  Zicmann,  Zdtnow.and  Femberg, it  is  possible  throu.uh  stain- 
ing with  a  mi.xture  of  niethylene-hlue  and  eosin  {Romaiwivski-Hium)  to  demonstrate 
within  the  majority  of  bacteria  a  "nuclear  suhstance"  or  "chromatin"  {Zi'^mann, 
Zettnoic)  or  a  "nucleus"  (Feu'bcrg) — that  is,  there  may  he  demonstrated  within  the 
bacteria  structures  of  varying  size  which  stain  red  like  the  nuclei  of  nialarial  jjlasmodia 
(Ronianoicski)  or  of  other  protozoa  or  of  tissue-cells,  wliile  the  cell-plasma  takes  a 
blue  stain.  According  to  Nakanishi,  circumscribed  nuclei  are  found  in  young  forms. 
The  Roj7ianowsk i-stain  is  a  mi.xture  of  methylene-blue  and  eosin,  whereby  a  red 
dye  contained  in  methylene-blue  (.Rosin,  Bed.  klin.  Woehen.,  1899;  Xocht,  Cbl.f.  Bakt.. 
1899)  is  precipitated.  Zettnow's  formula  is  as  follows:  50  c.c.  of  a  one-per-cent 
solution  of  a  Hdchst  methylene-blue  is  treated  with  3-4  c.c.  of  a  five-per-cent  solution 
of  soda.  To  2  c.c.  ov'  this  there  is  added  drop  by  drop  while  shaking  1  c.c.  of  a  one-jjor- 
cent  .solution  of  Hachst  eosin  BA.  Stain  five  minutes  on  cover-glass  and  examine  in 
water. 

.\ccording  to  Nageli,  Zopf,  and  others,  many  fission-fungi  possess  a  membrane  of 
cellulose  or  of  a  carbohydrate  closely  related  to  cellulose.  Certain  bacteria  (red  sul- 
phur bacteria)  combine  within  their  cell-substance  coloriTig-matter;  others  (BaciUiis 
amylobader ,  Spirillum  amijloferum)  give  at  certain  stages  of  their  development  the 
starch  reaction  with  iodin. 

Babes  and  Frnsf,  by  means  of  especial  staining  methods  uitli  T.ntJJvr's  methylene- 
blue,  ha^matoxylin,  and  Platvcr's  nuclear  black,  liave  demonstratccl  the  presence  of 
granules  within  different  forms  of  bacteria,  which  according  to  their  behavior  probably 
stand  in  some  relation  to  the  processes  of  division  and  spore-formation.  Ernst  desig- 
nated the  appearances  seen  by  him  as  sporogenous  granules,  since  he  was  able  in  certain 
bacteria  to  demonstrate  their  transition  into  spores;  he  is  inclined  to  regard  them  as  of 
the  nature  of  cell-nuclei,  a  view  which  Biitschli  also  favors.  Bunge  regards  the  gran- 
ules described  by  Ernst  as  cell-granules  which  have  nothing  to  do  with  spore-forma- 
tion, and  describes  other  granules,  which  stain  with  Loffler's  methylene-blue,  as  the 
forerunners  of  spores.  Marx  and  Woithe  regard  the  Babes-Ernst  granules  as  not  being 
nuclei  in  the  ordinary'  .sense  of  the  word,  but  as  representing  jjroducts  of  the  maximal 
condensation  of  the  euchromatic  substance  of  the  cells,  which  are  a  sign  of  the  highest 
intensity  of  vitality  on  the  part  of  the  cell.  Wagner,  on  the  contrary,  holds  that  cer- 
tain bodies,  wliich  he  has  observed  in  typhoid-  and  colon-bacilli,  are  nuclei. 

According  to  Xakanishi,  the  spores  form  (in  anthrax-  and  hay-bacilli)  by  a  concen- 
tration of  the  chromophile  substance  about  the  nucleus,  while  the  remaining  portion  of 
the  protoplasm  becomes  clear;  a  membrane  is  then  formed  about  the  chromatin  body, 
it  takes  on  a  fat-like  shine,  and  loses  its  power  to  take  stains  (methylene-blue  lib). 

The  bacteria  are  able  to  take  the  carbon  necessary  for  their  growth  from  most  of 
the  carbon  compounds  which  are  soluble  in  water.  They  can  al.so  derive  their  carixm 
from  dilute  solutions  of  substances  which  in  greater  concentration  are  injurious  to  them 
—as,  for  example,  from  benzoic  acid,  alcohol,  .salicylic  acid,  plienol.  etc. 

Their  nitrogen  is  derived  from  albuminous  matter;  further,  troin  those  comi)ounds 

designated  as  amins   (methyl-,  ethyl-,  propylamin),  amido-ariils  (asparagin,  leucin) 

and  amides  (oxamide,  urea),  as  well  as  from  the  amtnonia-sults  and  in  part  al.so  from 

i    nitrates.     The  albuminates,  previous  to  their  assimilation,  are  changed  into  i)ept()ne 

'    by  means  of  a  ferment  given  off  from  the  i)acteria.     Free  nitrogen  cannot  be  a.ssimi- 

(    lated  as  such.     Nitrogenous  and  non-nitrogenous  compounds  are  not  oidy  assimilable 

!    as  such,  but  also  in  coml)ination.     The  fission-fungi  are  able  to  take  nitrogen  from 

ammonia  and  nitric  aciil  only  in  the  presence  of  organic  carbon  compounds. 

Sulphur,  according  to  Xdgeli.  is  essential  to  the  schizomycetes.  aiul  they  take  it 
from  sulphates,  sulphites,  and  hyposulphites.  'J'he  otlier  mineral  suf)stances  nien- 
tioned  above  are  derived  from  various  salts.     If  in  the  case  of  an  abundance  of  nutrient 


554 


THE    PATHOGENIC    FISSION-FUNGI. 


material  there  is  too  little  water  present,  all  further  growth  ceases;  yet  many  of  the 
fission-fungi  are  able  to  dispense  with  water  temporarily.  Spores  suffer  little  from 
drying. 

"  Many  bacteria  are  very  sensitive  to  acids,  so  that  even  a  slight  degree  of  acidity 
hinders  their  growth  (for  example,  anthrax  bacilli  and  the  Friinkel-Weichselbaum 
pneumococcus).  Others  are  able  to  grow  with  a  moderate  amount  of  acid  in  the 
nutrient  fluid.  As  a  general  rule  they  are  especialh^  sensitive  to  mineral  acitls,  but  the 
])rosence  of  a  large  amount  of  citric,  butyric,  acetic  and  lactic  acids  hinders  also  their 
multiplication.  In  this  conncvjtion  belongs  the  fact  that  the  products  of  decomposi- 
tion caused  by  the  fermentative  action  of  the  fungi  are  at  a  certain  degree  of  concentra- 
tion harmful'to  the  development  of  the  fungus,  and  finally  stop  its  growth  entirely. 
Thus,  for  example,  in  butyric-acid  and  lactic-acid  fermentation  the  amount  of  butyric 
or  lactic  acid  gradually  formed  finally  checks  the  multiplication  of  the  fungus.  A 
similar  result  occurs  in  the  bacterial  putrefaction  of  albumin,  since  the  products  of  the 
same,  such  as  phenol,  indol,  skatol,  phenylacetic  acid,  phenylproprionic  acid,  etc., 
hinder  the  further  development  of  the  bacteria.  To  alkalies  the  fission-fungi  are  less 
sensitive,  and  many  can  bear  a  rather  high  degree  of  alkalinity  in  the  nutrient  fluid, 
but  there  also  exist  forms  which  do  not  thrive  in  alkaline  fluids  (acetic-acid  fungus). 

According  to  the  investigations  of  Pjeffer  and  Ali-Cohen,  many  motile  bacteria  show 
ctiemotactic  properties — that  is,  they  are  attracted  or  repelled  by  certain  chemical 
substances  dissolved  in  water.  Bacteria  swimming  about  in  fluids  collect,  therefore, 
at  places  where  there  are  chemical  substances  which  attract;  for  example,  typhoid- 
bacilli  and  cholera-spirilla  are  attracted  by  potato-juice  {Ali-Cohen).  Potassium 
salts,  peptone,  and  dextrin  likewise  attract,  but  the  individual  forms  of  bacteria  be- 
have very  differently  toward  these  substances  {Pfeffer).  Free  acids,  alkalies,  and 
alcohol  have  a  repelling  action. 


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Rieder.   Wirkung  d.  Rontgenstrahlen  auf  Bakterien.     Munch,  med.  Woch.,  1898. 
Romanowski :  Zur  Frage  der  Parasitologic  u.  Therapie  d.  Malaria,  1891. 
de  Rossi:  Metodo  sempl.  per  colorare  le  eilic  dei  batteri.     A.  per  le  Sc.  Med.,  xxiv., 

1900. 
Roux;  De  Taction  de  la  luraiere  et  de  I'air.     Ann.  de  I'lnst.  Past.,  i.,  1887. 
Salkowski:  Antiseptische  Wirkung  d.,  Chloroformwassers.     Deut.  med.  Woch.,  1888. 
Sames;  Bei  hoheren  Temperatureu  wachsende  Bakterien.     Zeitschr.  f.  Hyg.,  xxxiii., 

191)0  (Lit.). 
Sata:  Fettbilduug  durch  verschiedene  Bakterien.     Cbl.  f.  allg.  Path.,  1900. 
Schottelius:  Kernartige  Korper  im  Innern  von  Spaltpilzen.     Cbl.  f.  Bakt.,  iv.,  1888; 

Disinticirende  Wirkung  einiger  Theerproducte.     Miinch.  med.  Woch.,  1890. 
Sirotinin:  Entwickelungshemmende  Stoffwechselproducte  d.  Bakterien.     Zeitschr.  f. 

Hyg.,  iv.,  1888. 
Sjobring:  Feber  Kerne  u.  Theilungen  b.  d.  Bakterien.     Cbl.  f.  Bakt.,  xi.,  1892. 
Soyka  u.  Bandler:  Die  Entwickelung  von  patliogenen  Spaltpilzen  unter  wechselseiti- 

U'ciu  E:intluss  ilirer  ZersctziuigspnMlucte.     Fortschr.  d.  Med,,  vi.,  1888. 
Teuscher:  Beitr.  z.  Desinfection  niit  Wasserdampf.     Zeitschr.  f.  Hyg.,  ix.,  1890. 
Wag-ner;  Coli-  u.  Typhusbacillen  sind  einkernige  Zellen.     Cbl.  f.  Bakt.,  xxiii.,  1898. 
Wernich:  Desinfection.     Eulenburg's  Kcalcncyklop.,  1894  (Lit.). 
Wesbrook:  Effects  of  Sunlight  on  Tetanus  Cultures.     Journ.  of  Path.,  iii.,  1894. 
Zettnow:  Ronianowski's  Farbung  bei  Bakterien.     Zeitschr.  f.  Hyg.,  30  Bd.,  1899; 

Dent.  med.  Woch.,  1900. 
Ziemann:  Ucber  Mahiria  u.  andere  Blutparasiten,  1898. 

S  140.  The  growth  and  multiplication  of  the  fission=fungi  give 
rise  always  to  chemical  transformations  of  the   nutrient   material, 

which  ar«'  l)i()iij;lit  ;ibt)iit  in  part  through  the  intiueiice  ot"  fenncnts  pro- 
duced by  the  hactctla,  ami  in  part  directly  through  the  metabolic  processes 
OCCurr'uHj  iriihin  ike  cell.s  ilicinsrJrt's. 

Among  tlie  ferments  or  enzymes  are  to  be  mentioned  first  thej;/'o/^'- 
olytic  or  olbiDiiin-disfioIrinf/  eiizi/iiic.s  {iKieteriotrypsins)  which  bring  about  a 
solution  of  the  albuminous  bodies  and  cause  the  disintegration  of  the 
peptone-molecule.  Further,  bacteria  give  rise  to  diast (die  ferments  which 
convert  stai-ch  into  sugar,  also  to  inrertiuf/  fer mods vrhicli  transform  cane- 
sugar  ((li.sacchaiid  )  inlo  grape-sugar  (  monosaccharid). 

Tlie  chemical  results  of  bacterial  metabolism,  which  are  brought 
about    by  the  \  ital  activities  of  the  ti.ssion -fungi  aided  by  the  enzymes 


GEXEKAI^    .MOHPIIOLOOV    AM)     JilOI.OGY.  557 

l)roduced  by  them,  consist  in  tlie  iirst  place  of  ;i  deconiposilion  of  com- 
plex organic  componnds.  By  many  anthors  all  these  i)rocesses  are  desig- 
nated as  fermentations,  Mhile  others  (  Lehmann)  speak  of  iV'rmcntation 
only  when  a  tission-fnngns  breaks  down  a  given  food-material  with  es])c- 
cial  ease,  theivby  gi\  ing  rise  to  one  or  more  esjx^cial  ])roducts  in  marked 
quantity,  in  association  with  oi-  in  place  of  its  other  mt'tabolic  ])ro(lucls. 
Other  anthoi-s  still  narrow  the  term  fermentation  to  tlu^  decomposition  of 
carbohydi-ates. 

In  the  decompositions  caused  by  the  fission-fungi  very  different 
products  are  formed,  which  vary  according  to  the  composition  <tf  the 
nutrient  material  and  the  character  of  the  lissi<ui-fungus.  For  the  ])ro 
(luction  of  fermentation  a  proper  fermentable  nuiterial  is  necessary, 
^[any  fungi  are  able  to  cause  fermentation  in  the  ]uesence  as  well  as  in 
the  absence  of  oxygen,  while  to  some  of  them  a  lack  of  oxygen  is  neces- 
sary. 

Among  the  products  of  bacteria  of  especial  importance  to  the  ])hysi- 
cianare  those  which  have  a  poisonous  action  and  cause  tissue=changes, 
to  which  belong  pai'ticularly  those  substances  which  are  desci-ihed  as 
jytoma'ins,  foxiiis,  and  (endotoxins. 

The  ptomains  are  basic,  crystallizable,  nitrogenous  jn-oducts  of  the 
bacterial  decomposition  of  albumin;  they  are  '.\\so  known  i\s put nf active 
alkaloids  or  cadaveric  alkaJoids.  They  show  in  part  poisonous  properties. 
The l)est  known  are  sepsin,  putrescin  (dimethylethylendiamin),  cachuei-- 
in  (pentamethylendiamin),  collidin  (pyridine  deii\  ati\e),  peptotoxin, 
ueuridin,  neurin,  choliu,  gadinin,  and  substances  resembling  muscarin. 

The  true  toxins  are  specific  bacterial  poisons  produced  by  pathogenic 
bacteria  and  are  secreted  by  the  latter,  giving  rise  to  the  severe  symj)- 
toms  produced  in  diphtheria,  tetanus,  and  sausage  poisoning.  The  en- 
dotoxins are  substances  clinging  to  the  bacterial  cells  that  also  have  a 
poisonous  action.  In  the  bacterial  cell  there  occni-  also  the  bacterial 
proteins  which  give  rise  to  local  tissue-necrosis  and  inllammation.  The 
significance  of  these  substances  in  the  infectious  diseases  has  alieady  been 
mentioned  in  §  11. 

Among  other  decompositions  produced  by  bacteria  the  following  are  worthy  of 
note:  the  formation  of  lactic  acid,  formic  acid,  acetic  acid,  propionic  acid,  butyric  acid, 
often  also  the  formation  of  alcohol  and  carbonic  acid  from  sugar;  the  formation  of 
acids  (acetic,  butyric,  propionic,  valerianic,  succinic,  formic,  and  carbonic)  from 
alcohol  and  organic  acids;  the  formation  of  indol.  skatol,  phenol,  cresol.  pyrocatechin, 
hydrochinon,  hydroparacumaric  acid,  and  paroxyphenylacetic  acid  (ron  .\rnrki, 
SalkowsLi ,  Brieger),  and  finally  hydrogen  sulphide,  ammonia,  carbonic  acid,  and 
water  from  albumin;  the  formation  of  anunonium  carl)onate  from  urea:  the  trans- 
formation of  nitrous  and  nitric  acids  into  free  nitrogen;  the  reduction  of  nitrates  to 
nitrites  and  to  ammonia,  etc.  Finally,  there  are  also  bacteria  living  in  the  .soil— the 
nitro-bacteria — which  are  able  to  form  nitrous  and  nitric  acids  from  anunoniu  {Wino- 
gradsky).  •       ,  ,  , 

Along  with  the  nitrification  of  nitrogen  there  occurs  smuill.ineously  a  decom- 
position of  earthy  alkali  carbonates,  as  .shown  by  the  fact  that  the  nitrobacteria  arc 
able  in  the  presence  of  organic  carbon  compounds  to  derive  from  the  rnrbonatcs  the 
carbon  necessary  to  the  building-up  of  tlie  cells.  There  takes  place,  therefore,  through 
the  vital  activity  of  these  organisms,  a  synthesis  of  organic  material  out  of  inorganic 
substances. 

Under  the  influence  of  the  fi.ssion-fungi  there  are  formed  bitlrr.  sharp,  miuscating 
substances  (bitter  milk).  Further,  bacteria  occasionally  produce  jiigmcuts  of  a  red. 
yellow,  green,  blue,  or  violet  color.  For  examjjle.  Hacillus  pmdigiosns  produces  a 
blood-red  coating  upon  bread  (bleeding  bre;id);  bandages  and  pus  t;ike  on  a  bluish- 
green  color  as  the  result  of  the  presence  of  the  Bacillus  pyocyancus.  In  many  cultures 
there  is  also  formed  a  fluorescent  colorinsr-matter. 


558  THE    PATHOGEXIC    FISSIOX-FUNGI. 

The  fihnsphorescence  not  infrequently  seen  upon  decomposing  sea-fish  depends 
also  upon  Ixicterial  products  of  decomposition,  as  has  been  shou-n  by  PflUger,  and 
appears  when  there  is  an  active  multiplication  of  the  bacteria. 

Literature. 

{Chemical  Changes  Produced  by  Schizomycetes.) 

Baumann  u.  v.  Udranszky:  Vorkommen  von  Diaminen  (Ptomainen)  bei  Cystinurie. 

Zritschr.  f.  pliys.  Chcm.,  xiii.,  1889. 
Bocklisch.  Faulnissl)aseu  aus  Fischen.     Ber.  d.  Deut.  chem.  Ges..  xviii.,  1885. 
Brieger:   Uebcr  Ptomaine,  Berlin,  1885,  1886;  Berl.  klin.  Woch.,  1880;  Zusammenset- 

7,ung  des  Mytilotoxins,  nebst  einerUcbersicht  der  bisher  in  ibrcn  Hauptt-igcnscliaf- 

tcn  bekannten  Ptomaine  und  To.xine.     Virch.  Arch.,  115  Bd.,  1889;  Bakteriengifte. 

Zcitschr.  f.  Hyg.,  xix.,  1895. 
Buchner:  Activelosliche  Zellproductce.     Miinch.  med.  Woch.,  1897. 
Cahen:  Ueb.  d.  Reductionsvermogen  d.  Bakterien.     Zeitschr.  f.  Hyg.,  ii.,  1887. 
Duclaux:  Ferments  et  maladies,  Paris,  1892. 
Eijkman:  Enzyme  der  Bakterien.     Cbl.  f.  Bakt.,  xxix.,  1901. 
van  Ermengem:  Anaerob.  Bacillus  u.  seine  Bez.  z.  Botulismus.     Zeitschr.  f.  Hyg.,  26 

Bd.,  1897. 
Fermi:  Die  Leira  und  Fibrin  losenden  u.  die  diastatischen  Fermeute  der  Mikroorgan- 

ismeu.     Cbl.  f.  Bakt.,  vii.,  1890. 
Forster:  Ueb.  einige  Eigenschaften  leuchtender  Bakterien.     Cbl  f.  Bakt.,  ii.,  1887. 
Gamaleia:  Les  poisons  bacteriens,  Paris,  1892. 
Gautier:  Sur  les  alcalo'ides  derives  de  la  destruction  bacterienue  on  physiologique  des 

tissus  animaux,  ptomaines,  et  leucomai'nes.    Paris.  1886. 
Husemann:  Ptomaine.     Arch.  d.  Pharmacie,  1880-83. 
Ingenkamp:  Unsere  Kenntuisse  v.  Faulniss  u.  Githrung.    Zeitschr.  f.  klin.  Med.,  x., 

LSS.'). 
Krannhals:  Ueb.  Kephir  u.  lib.  den  Kephirpilz.     Deut.  Arch.  f.  klin.  Med.,  xxxv., 

18>4. 
Lassar:  Die]\Iikrokokken  der  Phosphorescenz.    Pfliiger's  Arch.,  xxi.,  1880. 
Llideritz:  Zur  Keuntn.  d.  auagroben  Bakt.     Zeitschr.  f.  Hyg.,  v.,  1888. 
Ludwig:  Die  bish.  Untcrs.  iiber  pathogene  Bakterien.     Cbl.  f.  Bakt.,  ii.,  1887. 
V.  Nencki:  Zersetzung  d.  Gelatine  u.  d.  Eiweisses  bei  d.  Faulniss  mit  Pankreas,  Bern, 

1874;  verschied.  Arb.  im  Jouru,  f.  prakt.  Chem.,  im,  .Tourn.  f.  phys.  Chem.  u.  in  d. 

Ber.  d.  Deutsch.  chem.  Ges.  a.  d.  J.   1876-81 ;  Die  Anaerobieu  u.  d.  Gahruugen. 

Arch.  f.  exp.  Path.,  xxi.,  1886. 
Oppenheimer:  Toxine  u.  Antitoxine.,  Jena,  1904. 
Pfliiger:  Pfliiger's  Arcii.,  1875;  Phophorescenz  der  lebendigen  Organismen.     Arch.  f. 

d.  ui's.  Phys.,  X..  1875;  Phosphorescenz  verwesender  Organismen.      lb.,  xi.,  1875. 
Podwyssozki:  Kephir,  Petersburg,  1894. 
Salkowski:  Zahlr.  Arb.  i.  d.  Ber.  d.  Deut.  chem.  Ges.;  Zeitschr.  f.  phys.  Chem.  aus 

dm  Ict/.tcn  Jahrzehnten. 
Vaughan  and  Novy :  Cellular  Toxins,  1902. 
"Winogradsky:  Kccli.  sur  les  organismes  de  la  nitrilication.     Ann.  de  I'lnst.  Pasteur, 

isiio.  is!)l. 
Wortmann:  Ueb.  d.  diastatische  Ferment  d.   Bakt.     Zeitschr.   f.   phys.  Chem.,  vi. ; 

Pllanzl.  Verdauungsprocesse.     Biol.  Cbl.,  iii. ;  Organismen  d.  Xitritication  u.  ihre 

l.hysiol.  Bedeutung,  Landwirthsch.  Jahrb.,  xx.,  1891;  ref.  Bakt.  Cbl.,  x.,  1891. 

See  also  ^   11. 


2.  General  CoNsiDER.iTioNS  Concerning  the  Pathogenic  Schizo- 
mycetes AND  their  Behavior  in  the  Human  Organism. 

§  150.  As  has  already  been  explained  in  §  11,  there  are  among  the 
schizomycetes  numerous  species  which  are  capable  of  causing-  disease- 
processes  in  the  human  organism,  and  are  therefore  called  pathogenic 
schizomycetes.  The  first  condition  of  such  action  is  evidently  that  the 
bacteria  concerned  must  possess  properties  enabling  them  to  multiply  in 
the  tissues  of  the  living  human  body.  They  must  therefore  find  in  the 
tissues  the  suitable  nutrient  material,  and  in  the  body-temi)erature  the 


PATllOCiKXKSIS.  550 

warmth  necessaiy  to  tlieir  growth.  Tho  tissues,  moreover,  imisi  imt 
Cont:iin  substances  Avliieli  are  a  liiiHlranee  to  tlieir  .urowtli  (d".  ij  .".1  i. 

If  pathogenic  fission-fungi  succeed  in  growing  in  tlje  tissues  of  the 
body,  if  infection  takes  phice  (cf.  §  11),  their  action  is  in  gcncial  char- 
acterized l>y  tlie  production,  ((f  the  point  of  muKipUcdt'Kni,  of  tissiir-<lr(/rnrr- 
(iti(»is.  necrosis,  inJlahunatioH,  and  iirir-f/rotr(li.s  of  fissKc,  \\hiU>  at  tlie  same 
time  the  toxins  i)roduced  by  them  cause  nuiniOstdtions  of  poisoninr/. 

In  indi\idual  cases  the  ])athoh)gical  i)rocesses  vaiy  greatly,  in  that 
the  distribution  of  the  bacteria  in  the  oigauism.  and  their  locnl  action, 
as^well  as  the  production  of  the  pitisons,  differ  gicatly  with  the  difreient 
forms  of  bacteria. 

With  many  the  local  action  upon  the  tissue  is  the  most  ]u-ominent 
cliaracteristic,  with  others  the  r/enrraf  intoxication.  ]\Iany  bacteria  confine 
tlicmscJrcs  to  the  region  in  irhich  tJici/  hare  (/ained  entrance  ;  otiiers  adrancc 
uninterniptetJIji  upon  the  surroiindinn  tissues  ;  othei's  still  ar«'  cai'ried  by  the 
blood  and  lymi)h  streams  and  lead  to  the  formation  of  metastatic  foci,  and, 
finally,  others  increase  irithin  the  blood. 

If  a  spread  of  the  bacteria  takes  place  througli  the  blood,  the  bacte- 
ria maij  pass  from  the  mother  to  the  fains  dui-ing  i)regnancy,  si  net;  the 
placenta  forms  no  certain  tilter  against  pathogenic  bacteria.  This  lias 
been  demonstrated,  for  example,  in  the  case  of  anthrax-bacilli.  l)acilli 
of  symptomatic  anthiax,  glandei'S-bacilli,  spirilla  of  iclapsing  fe\<'r, 
typlioid-bacilli,  the  pneumococcus,  and  the  tubercle  bacillus.  According 
to  observations  of  Malvoz,  l>ii-ch-lliischfeld,  and  Lai  is,  changes  in  the 
placenta,  such  as  ha-morrhages,  h)ss  of  epithelium,  and  alterations  of  the 
vessel-walls,  faAor  the  passage  of  bacteria.  ]Moreo\-er,  bactei'ia — as,  f<.)r 
example,  anthrax-bacilli — can  grow  through  the  tissue-si)aces.  In  gen- 
eral the  passage  of  bacteria  from  the  mother  to  the  fcetus  ])resui) poses 
that,  after  the  entrance  of  these  organisms  into  the  cii'cuhiting  blood  of 
the  mother,  the  latter  shall  remain  alive  at  least  long  enougli  to  allow  of 
the  passage  of  the  bacteria  into  the  fietus. 

The  bacteria  Avliich  succeed  in  multiplying  within  the  human  oigan- 
ism  die  out  again  in  many  cases  within  a  short  time;  and  the  disease  jtro- 
duced  by  them  may  proceed  to  recocery  (cf.  §  31),  Ne\ertheless,  it  not 
infre(piently  happens  that  they  are  preserved  for  a  longtime  within  tlie  hod//, 
and  either  excite  a  continuous  disease  process,  or  at  times  remain  in  a  con- 
dition of  inactivity,  so  that  no  pathological  pi'ocesses  aie  r<'coguizable 
until  after  alonger  or  shorter  period  if  latency,  an  act  ire  reproduction  again 
takes  place  and  manifestations  of  disease  show  theniselres  anew. 

Not  infie((uently  a  secondary  infection  associates  itself  with  an  infec- 
tion already  existing.  The  relation  between  the  two  infections  is  either 
that  the  second  infection  followsthe  lii-st  accidentally,  or  that  throiigli  the 
first  infection  the  soil  is  i)repared  for  the  second  ( cf.  S  H)- 

Finally,  there  not  infrequently  occur  double  infections,  in  that  two 
or  more  forms  of  bacteria  develop  coincident  1>  in  the  tissues,  and  pio- 
duce  their  characteristic  injui'ions  inllneiice  n|)on  the  latter. 

Each  i)athogenic  tission-fungus  has  a  specific  action  upon  the  tissues 
of  the  human  organism  ;  but,  ne\'ertheless,  dijferent  sjxcies  ma//  exert  a  simi- 
lar action.  For  example,  there  aie  \arious  bactei-ia  capable  of  producing 
suppuration.  Only  in  a  certain  proportion  of  cases  do  the  i)athological 
tissue-changes  show  .such  si^ecitic  characteristics  that  from  these  the  spe- 
cies of  the  pathogenic  fission-fungus  can  be  i-ecoguized  with  certainty. 

Furthei-,  it  has  l)eeu  demonstrated  that  pathogenic  properties  of 
bacteria  are  by  no  means  constant ;  that,  on  the  cont  iai.\ ,  their  viin- 


5G0  THE    PATHOGENIC    FISSION-FUNGI. 

lence  varies,  so  tliat  bacteria,  which  cause  severe— that  is,  fatal— infec- 
tious may  become  cbauged  (weakened)  through  external  influences,  so 
that  they  either  wholly  lose  their  power  of  causing  disease-processes  iu 
the  organism,  or  at  least  cause  only  mild  forms  of  disease.  This  pecu- 
liarity is  not  alone  of  theoretical  interest,  but  is  also  of  great  practical 
importance.  It  explains  to  a  certain  extent,  on  the  one  hand,  why  a 
certain  infection  does  not  always  run  the  same  course,  and,  moreover, 
why  along  with  severe  attacks  light  ones  also  occur.  On  the  other  hand, 
it  affords  us  the  possibility  of  obtainiug  material  for  inocuJation  from 
attenuated  cultures  of  bacteria,  by  means  of  which  mild  grades  of  infec- 
tion or  intoxication  can  be  i^roduced,  which  are  able  to  protect  the  organ- 
ism from  severe  infections  or  to  bring  about  the  cure  of  au  infection 
already  acquired  (cf.  §  32). 

Weakening  of  the  pathogenic  properties  of  a  f ission=fungus  can  be 
biought  about  tlirongh  the  suitable  action  upon  cultures  of  the  same,  by 
high  temperatures,  oxygen,  light,  or  chemical  antiseptic  substances,  as 
well  as  by  the  cultivation  of  the  fungus  in  the  body  of  a  less  susceptible 
animal.  In  some  forms  it  is  only  necessary  to  cultivate  the  bacteria  in 
question  for  sometime  upon  artificial  media  (diplococcusof  pneumonia), 
or  to  expose  the  culture  to  the  air  for  some  time  (bacillus  of  chicken- 
cholera),  iu  order  to  bring  about  an  attenuation.  If  it  is  desired  to  pre- 
serve the  virulence  of  the  pneumococcus  for  some  time,  it  is  necessary, 
from  time  to  time,  to  pass  the  bacteria  cultivated  upon  artificial  media 
through  ]-abbits,  which  are  very  susceptible.  The  glanders-bacilli,  tu- 
bercle-bacilli, and  the  cholera-spirilla  lose  virulence  when  cultivated 
uninterruptedly  upon  artificial  media  for  some  time.  The  streptococcus 
of  erysipelas  (Emmerich)  becomes  so  attenuated  through  continued  cul- 
tivation in  bouillon  or  nutrient  jelly  that  it  is  no  longer  capable  of  kill- 
ing even  mice. 

As  to  the  nature  of  the  attennation  of  virulence  of  bacteria  by  the 
methods  mentioned  above,  it  is  possible  to  give  only  hypotheses.  If  the 
bacteria  cultivated  for  a  long  time  upon  artificial  media  change  in  viru- 
lence, this  maj^  perhaps  be  explained  in  i^art  by  assuming  that  in  a  series 
of  generations  the  less  virulent  varieties,  which  surely  often  arise,  grad- 
ually gain  the  upper  hand.  For  the  attennation  of  virulence  by  heat, 
chemical  agents,  etc.,  such  an  explanation  is  not  adequate.  In  this  case 
there  is  very  probably  a  general  weakening  or  degeneration  of  the  proto- 
plasm, and  in  harmony  with  this  theory  is  the  fact  that  such  bacteria 
show  a  diminution  in  energy  of  growth. 

If  tlie  presence  of  bacteria  be  suspected  in  auj-  tissue-lluid  or  iu  the  tissue-paren- 
rliyin:i,  tlicir  demonstration  may  tirst  be  attempted  by  means  of  a  microscopical 
Investigation.  Occasionally  this  is  successful  by  the  mere  examination  of  a  drop  of 
the  suspected  tluid  or  of  a  smear-preparation  of  the  tissue- juice  diluted  with  salt-solu- 
tion or  distilled  water.  In  other  cases  it  is  necessary  to  employ  staininfi  metJwds,  in 
which  case  cover-glass  smears  of  the  fluid  are  made  and  allowed  to  dry.  The  smeared 
cf)ver-glass  is  then  fixed  by  passing  through  the  flame,  and  after  cooling  is  stained. 
For  this  purpose  methylene-blue  is  preferably  employed,  in  a  preparation  of  a  one- 
per-cent.  methylene-blue  solution  in  a  1-to- 10, 000  solution  of  caustic  potash.  Water 
solutions  of  fuchsin  and  iiictliyl-violet  are  also  frequently  used.  For  many  bacteria 
there  are  employed  especial  staining  methods,  in  which  ord'inarily  the  preparations  are 
heavily  overstained  witli  a  solution  of  gentian-violet  or  fuchsin  iuaniline  water,  or  with 
a  water  solution  of  methyl- violet,  the  excess  of  stain  tlien  being  removed  by  means  of 
weak  acids  or  l)y  iodine  and  alcohol  {Gra/i/'s  method).  In  this  way  it  is  often  brought 
about  that  the  l)acteria  alone  remain  stained,  often  certain  forms  of  "bacteria  onlj'. 

When  it  is  desired  to  demonstrate  the  presence  of  bacteria  in  tissues,  small  portions 
of  the  tissue  are  hardened  in  formalin  or  in  absolute  alcohol,  and  are  then  cut  into  the 
thinnest  jyomhlc  Ktctions,  tr/tich  are  stained  by  appropriate  methods.    Here  again  the 


rATllOCEXKSIS. 


561 


ontian-violct,  niotliyl- 
scopir  I'Xiiiniiiiilion;  if 
(•(tiulciiser   slioulil    l)o 


(IcIllOIl- 
ll'tllods 

liiiiiiiiir 
P 


nietlioiis  most  frctiucntly  employed  ure  those  ineiitioiied  altove: 
violet,  aud  fuehsin.  Good  objeetives  are  necessary  I'or  tlic  iniei 
possible,  oil-immersiou  lenses  aud  illumiuatiou  \vitli  siibstayi 
employed. 

If  tlirouiili   any   imtliod  the  presence  of  bacteria  in  the  tissue  lias  Ix 
strated,  theattcnijii  is  ne.xl  made  to  cultivate  iheni.      For  Ihis  purpose  ti 
developed   by    I\<>rl,  are  usually  emiiloyed.     Tiicse,  in   i)rincii)le,  consist  in 
first  a  fluid  containinij:  tlie  l)aclena,  by  means  of  scrapini,'  tlie  tissue  or  by  rubliinir 
pieces  of  tissue  in  sterilized  salt-solution.     This  lluid  is  tlieii  evenly  dislril)uted  i 
solution  of  gelatin  or  agar  which  lias  been  liquefied  by  warming;  and  the  mixture  is 
ilieu  poured  upon  horizontal  glass  plates,  solidifying  as  it  cools.'    Tiie  individual  bac- 
teria, or  spores,  thus  separated  from  each  other  develop  in  tin  firm  nutrient  medium. 

By  a  proper  application  of  this  metliod  there  are  obtained  in  the  layer  of  gelatin 
various  colonies  (Fig.  425),  which  dilTer  in  apjiearance  so  that  they  may  often  be  differ 
entiated  from  each  other  by  the  naked  eye  alone.  When  sutliciently  separated  from 
one  another,  the  individual  colonies  may  l)e  taken  uji  by  means  of  a  tine  jilatinum 
needle,  and  transferred  eitiier  to  a  boiled  potato,  or  !o  a  sterile  gelatin  plate,  or  streaked 
upon  the  surface  of  the  solidified  nutrient  fluid  in  a  test-tube.  Very  often  the  infected 
needle  is  stuck  into  the  solidified  transjiarent  medium  contained  in  a  test-tube. 

If  the  culture  on  the  gelatin  iilate  is  jnire,  and  if  the  entire  procedure  is  carried  out 
with  the  necessary  care  and  the  avoidance  of  contamination,  pure  cultures  may  be  ob- 
tained by  this  method.  In  stab-cultures,  as  well  as  in  smear-cultures  on  potatoes  or  any 
other  nutrient  medium,  special  peculiarities  often  show  ihemselves  which  make  it   i)oa- 


FlG.  42-'.— Gelatin  plate  coutalning  pellicle-like,  sinuate  cDloiiie-s  nf  small  liacilli,  and  small,  spherical,  white 
colonies  of  cocci.    Culture  made  from  the  exudate  of  a  purulent  peritonitis.    Reduced  one-Uilrd. 


sible  for  tlie  experienced  observer  to  recognize  the  form  of  bacteria.  At  times,  how- 
ever, it  is  necessary  to  make  a  thorough  microscopic  examination  of  the  colonies. 

It  is  evident  that  all  the  above  manipulations  must  be  carried  out  witii  care,  aud 
that  absolute  cleanliness  of  the  instruments  used — glass-plates  and  test-tubes— as  well 
as  perfect  sterilization  of  the  nutrient  medium  are  necessary.  The  proper  methods  of 
sterihzatiou  in  which  a  long-(;ontinued  heating  or  an  expo"sure  to  high  temperatures 
plays  an  important  role,  are  best  learned  in  properly  equipped  laboratories.  The  neces- 
sary guidance  is  furnished  in  the  various  books  on  bacteriological  methods  of  examina- 
tion, which  have  recently  ai)peared. 

An  infusion  of  meat  containing  peptone  aud  gelatin  is  commonly  emjiloyed  for 
making  plates.  It  consists  of  a  watery  infusion  of  choppecl  meat,  to  which  a  delinitc 
amount  of  peptone  and  salt  is  added.'  This  is  further  neutralized  with  carbonate  of 
soda,  and  cnf)Ugh  gelatin  is  added  to  give  a  solid  consistence  at  ordinary  temperatures. 
For  streak-  and  stab-cultures  this  same  gelatin  is  sometimes  used;  at  other  times  a 
jelly  made  of  a  mixture  of  a  watery  extract  of  meat,  i)eptoue,  and  agar-agar;  or  again 
blood-serum  which  has  been  coagufafed  by  warming. 

For  stab-cultures  the  jelly  is  allowed  to  solidify  within  tlie  test-tube  in  a  perpen- 
dicular position ;  for  streak-cultures  the  test-tube  is  kept  in  an  oblique  position  until 
the  jelly  is  set. 

Sterilized  bouillon  is  often  used  for  cultures.  The  inoculated  nutrient  media  are 
kept  either  at   rooni-tempcrature   or   at   higher   temperatures  in  an  incubating  oven 

3G 


562  THE    PATHOGENIC    FISSION-FUNGI. 

{'60^-40^  C).  Tlie  proper  nutrient  medium  to  be  used  in  individual  cases  must  be  deter- 
mined by  experiment.  Experience  has  shown  that  the  individual  bacteria  behave  very 
differently  in  tiiis  respect,  some  growing  best  upon  one,  others  upon  another  medium. 
To  the  nutrient  medium  there  are  often  added  with  advantage  such  substances  as  sugar, 
glycerin,  urine,  brain-substance,  etc. 

It  is  self-evident  tliat  the  processes  briefly  described  above  may  be  modified  accord- 
ing to  the  necessities  of  the  case.  For  example,  in  those  cases  in  which  it  is  necessary 
to  grow  tlie  bacteria  at  high  temperatures,  the  use  of  gelatin  should  be  avoided  and 
ao-u'r-agar  jilates  should  be  made  instead.  Occasionally  membranes  or  exudates  from 
nmcoiis  surfaces  (diphtheria)  or  small  bits  of  excised  tissue  are  placed  directly  into  the 
culture-medium.  When  it  is  desired  to  examine  the  cultures  directly  under  the  micro- 
scope, cultures  may  be  made  upon  glass-slides.  In  the  case  of  many  bacteria,  as 
cholera-spirilla,  the  use  of  hanging-drop  cultures  is  advised.  In  this  method  a  drop  of 
sterilized  bouillon  hangs  down  from  the  under  surface  of  a  cover-glass,  and  is  inocu- 
lated from  a  previously  cultivated  pure  culture  of  the  fungus.  The  cover-glass  is  tlien 
placed  over  the  excavation  in  a  hollow  ground-glass  slide.  Evaporation  is  prevented 
by  the  exclusion  of  the  outer  air  from  the  cavity  in  the  slide,  by  a  rim  of  oil  or  vaseline 
placed  beneath  the  edge  of  the  cover-glass.  By  this  method  the  multiplication  of  bac- 
teria can  be  observed  for  a  long  time. 

When  bacteria  are  sought  in  water,  a  definite  amount  of  the  suspected  water  is  dis- 
tributed in  gelatin,  and  jjlate-cultures  are  made.  E((rth  is  rubbed  up  with  sterilized 
salt-solution;  «//■  is  made  to  pass  in  definite  am.ount  through  a  sterilized  salt-solution; 
and  the  salt-solutions  thus  infected  are  then  mixed  with  gelatin,  and  from  this  gelatin 
plates  are  made. 

Ihe  culture  of  bacteria  on  a.u([  in  different  media,  accompanied  by  the  microscopic 
examination  of  the  different  stages  of  development,  serves  for  a  more  exact  characteriza- 
tt'i'/t.  (111(1  Ihcrdu/  for  the  diferentiatioii  of  the  species  of  the  bacteria  in  q/iesfio/i.  After  its 
jiropcrtics  1kiv('  ixiii  thoroughly  studied  in  this  way,  the  influence  of  the  bacterium 
upon  the  animal  organism  is  tested.  As  experimental  animals,  rabbits,  dogs,  guinea- 
pigs,  rats,  mice,  and  small  birds  are  most  frequently  employed.  The  bacteria  to  be 
tested  are  introduced,  sometimes  under  the  skin,  sometimes  directly  into  the  blood- 
current,  sometimes  by  inoculation  into  the  internal  organs,  sometimes  by  inhalation 
into  the  lungs,  or  sometimes  by  administration  with  the  food  into  the  intestinal  canal. 
Bacteria  can  be  regarded  as  pathogenic  for  a  given  animal  when  they  nuiltiply  within 
the  tissues  and  excite  disease  processes.  If  relatively  large  amounts  are  inoculated,  the 
animal  experimented  upon  may  die  under  certain  conditions,  even  if  the  bacteria  do 
not  increase  at  all  in  its  body,  since  the  poisonous  substances  formed  in  the  culture  and 
introduced  by  inoculation  often  suffice  to  kill  the  animal. 

Experience  has  taught  that  only  some  of  the  bacterial  infections  which  occur  in 
man,  when  inoculated  into  animals,  run  the  same  course  as  in  man,  and,  indeed,  only 
those  which  also  occur  otherwise  in  animals.  In  other  cases  the  pathogenic  fission- 
fungi  occurring  in  man  or  in  certain  animals  are,  it  is  true,  pathogenic  for  the  experi- 
mental animal,  but  the  pathological  process  shows  another  localization  and  another 
course.     In  a  third  case  the  experimental  animals  are  in  part  or  wholly  immune. 

Inversely,  fission-fungi  that  are  often  extremely  pathogenic  for  the  experimental 
animals  are  harmless  for  other  animals  or  for  man. 


Literature. 

{Methods  of  Badci-iolo(jic(d  Invest igai ion.  ) 

Abel:  Taschcnl)uch  f.  bakteriologische  Praktikanten,  Wi'irzburg,  1904. 

Fischer:   Vorlesim<>en  iiher  Bakterien,  Jena,  1903. 

Flligge:  Die  .MikroorganLsmen,  Leipzig,  ISSXi. 

Fraenkel,  C:   (irundi  iss  der  Bakterienkunde,  Berlin,  1S95. 

Friedberger:  Die  Methoden  der  Bakteriol.  Handb.  v.  Kolle  u.  Wassermann,  i., 
Jena,    1903. 

Gierke:  Techiiik  der  patholog.-anatom.  Untersuchungen,  Jena,  1904. 

Gunther:   i;iiifiihriiim  in  das  Studium  der  Bakteriologie,  Leipzig,  1902. 

Hueppe:    Die  .MctlKHlcn  der  I'.aktcricnforschung,  Wiesbaden,  1891. 

Matzuschita:   Baktci  idlcgische  Diagnostik,  Jena,  1902. 

Migula:    Baktcriologisehos  Praktikum,  Karlsruhe,  1892. 

Novy:   Laboratory  \\ork  in  Bakteriology,  1899. 

Nuniorc'U.s  articles  on  the  investigation  "^of  bacteria  are  found  in  the  Centralblatt  f. 
Y-'kteriologie.  Of  the  many  text-books  in  English  dealing  with  bacteriology  may 
oe  mentioned  those  by  Crookshank,  Sternberg,  Abbott,  Park,  McFarland,  Muir 
and  Ritchie. 


THE    COCCI. 


663 


II.  The    Different    Forms   of    Bacteria    and    the    Infectious    Diseases 
Caused   by  Them. 


I.  Tin-:   (\)t"t"i,   OK 


Sph.t: koi{ actek i a ,   a  n  i  > 
Caused  ey  Tiikm. 


Tin:  .Moui'.in    Tuocesses 


{(()   General  Comideratiotis  L'((/<inliii(/  l/ir  (\nri. 


§151.  The  cocci  or  coccaceae  (Zopf)  arc  bacteria  lliat  occur  exclu- 
sively iu  the  form  of  round  or  oval  or  lanceolate  cells.  In  their  niulti- 
l)lication  by  division  they  often  form  i)ecnliar  agj; reflations  of  cells, 
which  are  commonly  designated  by  special  names  according  to  the  char- 
acter of  the  different  forms  appearing.  Since  certain  forms  of  cocci  are 
especially  likely  to  develop  in  definitely  shaped  aggregations,  advantage 
has  been  taken  of  this  fact,  to  classify  them  in  difierent  species.  It 
should  be  noted,  however,  that  a  given  species  does  not  always  appeal-  in 
the  same  form,  but  may  vary  according  to  the  nutrient  conditions. 

Many  of  the  cocci  multiply  by  division  in  one  i>laiie  oidy — at  right 
angles  to  the  length  of  the  elongated  spherical  cell.     If  the  s])heres  re- 
sulting from  division  remain  together  for  some  time  in  the  form  of  double 
spheres,    and    if  this 
form     appears     with 
especial  frequency  in 
the  case   of  any  one 
species,    it  is   desig- 
nated as  a  diplococcus 


^4^j^?v/ 


« 


^ 

♦.*.;» 


m^ 


Fig.  426.— streptococcus  from  a  purulent  peritoneal  exudate  of  a  case  of  puer|)eral  peritonitis,    a. 
Single  cocci ;  /»,  diplococci ;  c,  streptococci  or  torula-cliains.     X  .5(XJ. 

Fig.  4?".— Colonies  of  micrococci  in  blood-capillaries  of  the  liver,  causinjr  metastatic  almcess-forniatlon. 
From  a  case  of  pyipinia.    Necrosis  of  liver-cells,    x  400. 

Fig.  428.— Cocci  grouped  In  tetrads  (merismopedia),  from  a  softening  infarct  of  the  lung.     X  500. 
Fig.  429.-Sarcina  ventriculi.     X  400. 


(Fig.  420, />).  If,  from  a  further  continued  division  of  the  cells  in  one 
plane,  rows  of  cocci  (torula  chains)  result,  these  aie  known  as  strepto- 
cocci (Fig.  426, c  ),  and  this  term  is  used  also  as  tlu^  name  for  a  group. 
If  the  division  of  the  cells  takes  place  irregularly,  and  tlu^  cells  ivmain 
together  in  small  collections  or  heajjs,  the  bacteria  are  usually  desig- 
nated  as    micrococci    fZopf)   (Fig.  427).      By  ()gst<»n    and    Kosenbach 


(lit 


;ilc  .so 
■ther 


the  name  staphylococcus  or  f/ra]>e-eorri(.s  lias  been  n.sed  to  i 
of  these  forms.  Largei- collections  of  cells,  which  arc  held 
a  gelatinous  substance  derived  from  thi;  cell-membranes 
designated  as  ^'oor/ZaYt  masses.  If  the  masses  of  cocci  ar( 
larger  collections  by  means  of  a  gelatinous  en\clope,  lliey  a 
as  aneococci  or  tuhe-cocci. 

To  those  cocci  which  remain   nnitetl  foi-  a  longtime  in  a  foincelled 
tab'et  (Fig.  428),  the  name  of  merismopedia,  tetracoccus  or  tablet-coccus 


il    into 
ken  of 


504  THE    PATHOGENIC    FISSION-FUNGI. 

was  applied  by  Zopf.  Others  class  such  bacteria  with  the  micrococci. 
The  cocci  that  go  by  the  name  sarcinae  are  characterized  by  division  in 
three  directions  of  space,  so  that  conii^ound  cubical  packets  of  spherical 
cells  are  formed  from  tetrads  (Fig.  429). 

The  cocci  not  infrequently  show  a  tremulous  molecular  motion  in 
fluids;  swarming  movements  have  not  been  observed  with  certainty. 
Spore-formation  has  not  been  demonstrated  in  the  majority  of  forms. 
According  to  Cienkowski,  Van  Tieghem,  and  Zopf,  the  Coccus  {leuconos- 
ioc)  mesentcrioides,  that  produces  a  frog-spawn-like  culture  on  sugar  or 
parsnips,  forms  arthrogeuic  spores,  in  that  some  particular  cell  in  a 
torula  chain  becomes  larger  and  glistening.  According  to  Prazmowsky 
the  Micrococcus  urea;  also  forms  spores. 

The  saprophytic  cocci  grow  upon  very  different  nutrient  substrata 
and  cause  by  their  growth  in  suitable  media  various  i^rocesses  of  de- 
composition. Many  also  form  pigments.  Micrococcus  nrcce  causes  a  fer- 
mentation in  urine  by  means  of  which  ammonium  carbonate  is  formed 
from  the  urea.  Micrococcus  viscosus  is  the  cause  of  the  slimy  fermenta- 
tion of  wine.  The  cause  of  the  j^^'^'-W^'orcsccncc  of  decomposing  meat  was 
found  by  Pfliiger  to  be  a  micrococcus  that  forms  slimy  coatings  on  the 
sui'face  of  the  meat. 

Of  the  pigment-producers  the  best  known  are  Micrococcus  luteus,  Mi- 
crococcus aurantiacus,  Sarcina  lutea,  Micrococcus  cyancus  and  Micrococcus 
violaceus,  which,  when  grown  upon  boiled  eggs  or  potatoes,  produce  yel- 
low, blue,  and  violet  pigment  respectively. 

Saprophytic  cocci  are  found  in  the  mouth  cavity  and  intestine,  as 
well  as  on  the  surface  of  the  skin,  and  occasionally  also  in  the  lungs. 
Micrococcus  hcematodes  (Babes)  is  said  to  be  the  cause  of  red  sweat,  and 
forms  red  zoogloea  masses. 

Sarcina  ventriculi  (Fig.  429)  occurs  not  infrequently  in  the  stomach 
of  man  and  animals,  especially  when  abnormal  fermentations  are  going 
on.  According  to  Falkenheim  the  stomach  sarcines  can  be  cultivated 
upon  gelatin,  and  form  in  this  medium  round,  yellow  colonies,  which 
contain  colorless  monococci,  diplococci,  and  tetrads,  but  never  cubical 
packets.  They  form  these,  however,  in  neutralized  hay-infusion,  and 
their  growth  causes  a  souring  of  the  infusion.  The  membrane  of  the 
sarciiue  is  said  to  consist  of  cellulose. 

Microcococcus  tetragenus  (merismopedia)  is  not  infrequently  found 
in  liuman  si)utum,  and  in  the  mouth  and  throat;  it  may  be  present 
furtlier  in  the  wall  of  tuberculoiis  cavities,  or  in  hsemorrhagic  or  gan- 
grenous foci  of  the  lungs.  It  forms  tetrads  (Fig.  428)  whose  cells  are 
held  together  by  a  gelatinous  membrane.  On  gelatin-iilates  it  forms 
i(»und  or  oval,  lemon-yellow  colonies.  It  is  pathogenic  for  white  mice 
and  guinea-pigs,  to  a  less  extent  for  rabbits,  and,  when  injected  subcuta- 
ncously,  excites  purulent  inflammations,  in  the  mouse  often  also  a  sep- 
1  ica'Hiia.  IntratiMcheal  injections  maj^  give  rise  to  inflammations  of  the 
r('S])irat<)ry  passages  and  the  lungs. 

The  pathogenic  cocci  cause  acute  inflammations  which  usually  heal 
after  the  deatii  of  the  bacteria;  but  it  not  infrequently  happens  that 
cocci  may  remain  in  the  body  for  a  long  time  and  give  rise  to  chronic 
l)rocesses. 


THE    rATlKXJKNIC    COCCl.  665 


Literature. 

{The  Cocci.) 

;:  Rothcr  Schwciss.     Riol.  Cbl.,  ii.,  1882. 
Bancel  ct  Hasson:  ,Siir  la  phosphorescence  de  la  viaiidc  ilc  Iiomanl.     ("oinpt.  rend.. 

t.  88,  1879. 
Bienstock:  Baktcrieii  d.  Daniies.     Fortsclir.  d.   :Med.,  i.  ;  Zcilschr.  f.  klin.  Med.,  vii., 

1884. 
Bosc  et  Galavielle:  Siir  le  micrococ.  tetrageiuis.     Arch,  de  ined.  ex  p..  IS'ii). 
Brieger:  IJaklerieii  des  Darmes.     Berl.  klin.  Woch.,  1884. 

Chauffard  et  Raymond:  Septicenue  tetrageuique.     Areli.  denied.  r\\\..  ISilC). 
Cohn;  Hcitriige  z.  Biologic  d.  Ptlanzen,  i.-iv. 
Eberth:  lilauer  Eiter.     Virch.  Arch.,  73  Bd.,  1878. 
Escherich:  Bakterien  d.  Darmes.     Fortschr.  d.  3Ied.,  iii.,  iss.l;  r.Iuiicii.  nied.  Woeli., 

188«. 
Falkenheim:  Ueber  Sarcine.     Arch.  f.  exp.  Path.,  xi.\.,  1885. 
Gessard:  De  la  pvocyanine  et  de  son  microbe.     These  de  Paris,  1882. 
Liicke:  Blauer  Eiter.     Arch.  f.  klin.  Chir.,  1892. 
Ludwig:  Micrococns  Ptliigeri  (Phosphoresceuz),  Iledwigia,  1884. 
Miller:  Die  ^likroorganismen  der  Mimdhohle,  Leipzig,  1892. 
Prazmowsky:  Ueber  Sporenbildung  bei  den  Bakterien.     Biol.  Cbl.,  viii.,  1888. 
Prove:  Micrococcus  ochroleucus.     Beitr.  z.  Biol.  d.  Pflanzen  v.  Cohn,  iv..  1S87. 
Schroter:  Pigmcntbildende  Bakterien.     Beitr.  z.  Biol.  d.  Ptlanzen,  v.,  Cohn,  i. 
Stubenrath:  Das  Genus  sarcina,  Mtinchen,  1897. 
Vignal:  Hech.  s.  I.  microorganismes  de  la  bouche.     Arch,  de  phys.,  viii.,  issii;  ]{rch. 

s.  1.  microorg.  des  matieres  fecales.     lb.,  x.,  1887. 

See  also  §  148. 

(h)  The  Pathogenic  Cocci. 

§  152.  The  Streptococcus  pyogenes  (Kosenbach)  is  a  coccus  which, 
in  multiplying:,  forms  (louble  spheres  and  ch<(in.s  of  spheres  (FU^.  42<))  of 
different  lengths,  containing  from  four  to  twelve  or  moi-e  cell^.  This 
chain-formation  comes  to  an  especially  full  develo])meiit  when  tiie  strep- 
tococcus is  growing  in  fluids — in  nutrient  bouillon  or  fluid  exii(lat«'s — but 
is  also  usually  seen  when  it  is  growing  within  the  tissues. 

The  cocci  stain  well  by  Gram's  method,  are  facidtative  auaeroln's, 
grow  best  at  37°  C,  and  form  small  whitish  colonics  on  gelatin  and  agar. 

Streptococcus  pyogenes  causes  in  man  inflammations,  irhich  usitalhi, 
though  not  always,  assume  a  purulent  character.  Occasionally  it  is  found 
also  upon  normal  mucous  mend)ranes,  for  exainph',  in  the  upper  aii-p;is- 
sage.s,  or  in  the  vagina  and  cervix  uteri;  it  may  tlier«'forc  be  ;i.ssnnied  in 
such  casesthat  its  virulence  is  very  slight,  or  that  the  mncons  membranes 
offer  a  succes.sful  resistance  to  its  entrance  into  theii-  tissnes. 

An  infection  with  streptococci  may  occur  either  in  healtli>  indi- 
viduals, or  in  those  who  have  received  some  injury,  or  tinally  as  an  ac 
companiment  and  secpiela  of  other  infections,  i)articularly  of  scarlet 
fever,  smallpox,  diphtheria,  and  pulmonary  tidierculosis. 

If  tlui  streptococcus  multiplies  upon  the  surface  of  mucous  nifiu/nauts 
—for  example,  of  the  resi)iratory  tract  (Fig.  4;{0)— it  excites  an  injlam- 
uiaiion,  wliich  may  bear  the  character  of  a  <hs(/uaniat  i  re  or  jfu  rnlcnf  catarrh 
(c),  or  of:  ii  croupous  exudation  (d).  If  it  penetrates  into  the  connective 
tissues  of  the  submucosa,  it  causes  most  frecpiently  inllammations  which 
2iTQ phlegmonous  in  character — i.e.,  amore  or  less  <iuickly  spreading,  .sero- 
purulent,  or  purulent,  or  fibrinoi)urulent,  or  serolibrinons  inilamnni- 
tiou,  which  may  at  certain  points  lead  to  sui)pnration   and  al»scess-for- 


566 


THE    PATHOGEXIC    FISSION-FUNGI. 


mation.     In  the  exudate  the  cocci  may  be  found  in  part  free  (Fig.  431, 
c),  or  in  part  inclosed  within  cells  (b). 


a</ 


o  ^^^^^^..^;^^ 


"^W^^"^ 


.■$P^^  b 


Fig.  430.— Streptococcus  tracheitis  In  scarlet  fever  (alcohol,  carmine,  methyl-violet,  iodine),  a.  Con- 
nective tissue;  l>,  desquamated  epithelium;  c,  membrane  composed  of  cells  and  streptococci:  tf,  flbrin- 
threads.    X  300. 

The  mult ijilicaf ion  of  streptococci  in  the  stratum  germinativum  of  the  skin 
leads  to  the  necrosis  of  epithelium  and  the  formation  of  jmrulent  vesicles 
or  blebs. 

If  the  streptococcus  spreads 
in    the    corium,    into    which    it  -  r         "x  -•' :  ^ 

penetrates  especially  in  the  case 
of  small  wounds  of  the  skin,  it 
utilizes  the  lymph-spaces  and 
lymph-vessels  (Figs.  432,  a;  433, 
h,  i;  434,  c)  as  pathways  and 
as  places  for  the  develoj)ment  of 
colonies,  causing  a  more  or  less 
severe  inflammation,  which  is 
characterized  macroscopically  by 
an  advancing  redness  and  swell- 
ing of  the  skin  known  as  er^ij- 
sipeJas.  To  the  external  appear- 
ances there  corresponds  a  more  or  less  severe  serous  and  cellular  in- 
filtration (Figs.  432,  d,  e,  f;  433,  m;  436,  c),  and  often  also  a  tibrino- 
cellular  exudation  (Fig.  433,  ««,).     The  infection  of  the  lymph- vessels 

in  erysipelas    involves   at 
^  y  times  chiefly  the  superficial 

layers  of  the  cutis  (Fig. 
433),  at  other  times  the 
deeper  layers  (Fig.  434, 
c).  In  the  latter  case  the 
erysipelatous  process  be- 
comes phlegmonous  in  i 
„     .oo    o,     .  ,  ,•   ,  s  ■     ,      ,      V,         character,  so  that  between 

Fig.  432.— .sfrfjiforoffx.s- ci-i/.-ipr/rtM.s  (a)insidea  lymph-  -i        ,  i 

vessel  (/().  in  pjirt  coinposfd  nf  thickly  crowded  spheres,  in  the  twO    prOCCSSCS  a   Sharp 

p;irt  of  tonil;i-.li;iiiis  (al.olK.l,  L'.'ntiaii-violet):  c,  neighbor-  hnrrlf^r    1  i  n  P     nnnot,     he 

licodof  the  l.viiii.h-v.ss.l.  with  pale,  non-staining  nuclei ;  d,  OOraCl-Hne     CaunOL     ue 

vein;  «?,  perivenous  cellular  inllllratiou  of  tissue;  /,  accumu-  draWU.       At  the  Same  timO 
liition  of  cells  in  the  lymph-vessel.    Section  of  rabbit's  ear  .,,     ,i         •_<.-•  j?    xt, 

two  days  after  inoculation  with  erysipelas-cocci.    X225.  With  the    imeCtlOn    01    the 


FIG.  431.— Streptococcus  pyogenes  from  a  phlegmon- 
ous focus  of  the  stomach  (alcohol,  carmine,  methyl- 
violet,  iodine) .  rt,  Leucocytes  ;  /),  leucocytes  containing 
streptococci ;  c,  free  streptococci.    X  500. 


STKEl'TdCOCCI. 


5G7 


deeper  layers  streptococci  may  spread  on  the  surface  of  llic  cpitlMliiini 
^that  is,  beneath  the  liorny  layer  (Fjo;.  4.'U,  i/),  and  ciiiisc  a  Iddsni- 
iug  of  the  epithelial  cells  and  a  dcstinamat ion  of  Ihc  luirny  layer  (  f ). 


is^^^^»---^-~-_.  :'-'--^-v-?Sj;^^~;ft^v    ^ 


Fig.  ^T:!  — Swtion  of  the  skin  in  crysiiiclas  bulldsuiii  (alnilml.  alnni-canniinO.  (/.  KpidiTiiiis;  b. 
corium  ;  c  Vfside;  (J,  covering  of  vcsiclt- ;  <.  r|iitlu'Jial  rt-lts  rdniaiiiintr  vai-uolcs  ;  I',  swollen  c.-lis  with 
swollen  nucli'i:  </,  0,,  eavity  caused  by  the  hiiiirfactimi  of  i-pitliclial  crlls.  ami  (■(mlaniiti!.'  fratrnu'nts  of 
epitheliuTii  and  jnis-corpuscles ;  /i,  lymph-vessel,  partly  llllcd  with  stn'ptuciH-ci ;  /.  lymph-vessel  tilled  full  of 
Streptococci;  /f,  colony  of  streptococci  in  the  tissue;  /,  ?i.  necrotic  tissue;  »;i,  cellular,  hi,,  llhrlniprellular 
Infiltration  ;  n,  flbrinoceilular  exudate  in  the  vesicle.    X  GO. 


:^' 


1f$ 


0 


Fig.  434.— Erysipelas  of  the  head  In  a  child  of  one  month  of  a<fe  (bacterial  stainlnpr.  cunulne) .  a.  Cutis 
with  hair-follicles;  h,  suhcutis;  c,  Ivmph-vessel  with  strepto<-occi  and  inflamed  surroiindiiiK  area;  if,  rete 
Malpighii ;  e,  f,  horny  layer  ;  y,  streptococci  lyin^  upon  the  rete  MalpiKlili.     X  4.5. 


568 


THE    PATHOGENIC    FISSIOX-FUXGI. 


Ill  cases  of  severe  infection  wifh  very  virulent  streptococci  tlie  pro- 
cess may  go  on  to  liquefaction  of  the  epithelium  (Fig.  433,  e,  f,  g, 
g),  and  to  the  formation  of  vesiclt^s  (('.  erysipelas  bullosum),    or  to  ne- 


m.- 


Fig.  435.— BeRinninff  streptococcus  phlegmon  on  the  trunk,  after  phlegmon  of  the  arm  (formalin,  car- 
mine, methyl-violet),  a,  h.  Skin  ;  c,  streptococci  in  the  subcutaneous  connective  tissue ;  (7,  beginning  col- 
lection of  leucocytes.    X  15. 

crosis  and  gangrene  of  the  corium  {J,  ?„  erysipelas  gaugrienosum),  or  to 
suppuration  of  the  tissue. 

In  the  subcutaneous  tissue  the  spread  and  multiplication  of  the  cocci 
(Fig.  435,  c )  lead  to  a  progressive  seropuruleut  (fZ)  and  fibrinopurulent 
inflammation,  often  with  subsequent  tissue-suppuration.  Such  forms  of 
infection  are  known  as  phlegmons. 

If  the  muscles  become  involved  in  a  phlegmonous  process,  the  strei^tococci 
increase  and  spread  (Fig.  436,  a)  chiefly  in  the  connective  tissue  of  the 
perimysium  internum,  but  may  penetrate  also  into  the  sarcolemma -tubes. 
Here  also  the  consequences  of  the  infection  are  more  or  less  severe  inflam- 
mations leading  to  suppuration. 

Bronchogenous  infection  of  the  lungs  causes  purulent,  or  croupous,  or 
ha-morrhagic  exudations  into  the  pulmonary  alveoli. 

Should  bone  become  involved  from  the  skin  or  from  a  mucous  mem- 
brane— as,  for,eiami)le,  from  the  middle  ear — the  cocci  may  increase  in 
very  large  nuilibers  in  the  marrow  tissue  (Fig.  437,  a,  b),  and  here  give 
ri.se  in  the  first  place  to  tissue-uecrosis,  and  later  to  a  purideut  inflam- 
mation of  the  neighboring  tissues. 


STKEPTOCOCCI. 


5G9 


-b 


-^^^i^mmm^ 


Fig.  436.— Streptococcus   phlegmon   in    muscle.     (Alcohol,  Weiprert's   siiiiii.1      <u    Miis.st's   of 
itreptococci;    h,  leucocj'te  infiltration;    c,  transverse  section  of  muscle-fibres.     X  100. 


M 


^^ 


FIG.  43r.-Streptocti(cus  infection  of  the  petrous  portion  of  the  temporal  bone,  from  u  ililld  of  elRlil 
months  of  age  (fonnalin,  nitiic-acid  decalciacation,  carmine,  methyl-violet).  <(.  Medullary  spaces  i-om- 
pletely  tilled  with  streptococci;  )>,  beginning  invasion  by  strepto<-oc<-l ;  c.  Inme  iiiarniw;  ./.  imiHTuUe  >if 
bone.    X  3(X). 


570 


THE    PATHOGENIC    FISSION-FUNGI 


A  streptococcus  infection  may  terminate,  either  sooner  or  later,  in 
that  the  opposing  forces  of  the  organism  restrict  the  further  spread  of 
the  bacteria,  and  destroy  them.  Not  infrequently,  however,  the  infec- 
tion prr)gresses  up  to  the  time  of  death. 

If  the  streptococci  break  into  the  lymph-  and  blood-vessels,  vietas- 
tases  are  often  formed,  and  distant  organs  are  in  this  way  involved. 
Infection  of  the  lungs  leads  easily  to  infection  of  the  'pleura.  Infection 
of  the  female  genital  tract,  which  easily  takes  place  during  delivery  and 
the  puerperium,  leads  very  often  to  a  spread  of  the  infection  to  the  peri- 
toneum by  means  of  the  lymphatics.  Infection  of  the  serous  membranes 
leads  usually  to  a  seropurulent,  or  fibrinopurulent  exudation,  the  strepto- 
cocci developing  luxuriantly  in  the  free  exudate,  and  forming  long 
chains.  In  infection  of  the  blood,  the  streptococci  do  not  increase  in  the 
circulating  blood,  but  at  the  jioints  where  they  come  to  rest ;  in  the  small 
capillaries  of  the  lungs,  heart,  liver,  kidneys,  spleen,  bone-marrow,  joints, 
etc.,  or  even  on  the  valves  of  the  heart.  At  the  ijoint  of  increase  there 
is  likewise  produced  an  inflammation,  which  in  general  bears  the  same 
character  as  the  primary  inflammation,  but  is  not  infrequently  less  severe 
and  more  circumscribed. 

Hcematogenous  streptococcus-infection  of  the  lung  leads  to  the  formation 
of  inflammatory  foci  (Fig.   438,  a),  wiiich  for  the  greater  part  show  a 


:h 


Fig.  43B.— Metastatic  baematogenous  streptococcus  pneumonia,  after  angina  (alcohol,  alum-carmine, 
methyl-violet,  iodine),  a,  Pneumonic  focus  with  (blue)  streptococci ;  b,  slightly  inflamed  lung  tissue  about 
ihe  focus.     X  «0. 

central  suppuration.  Collections  of  streptococci  on  the  surface  of  the 
endocardium  of  the  valves  or  of  the  heart  wall  (Fig.  439,  a)  lead  to  a 
superficial  necrosis  and  further  to  the  formation  of  coagula  (&),  collec- 
tions of  leucocytes  (&i)  and  proliferations  of  granulation  tissue  {c,  d). 
A  deeper  infection  with  the  streptococci  causes  an  extensive  necrosis  of 
the  tissue  accompanied  by  an  inflammation  of  the  surrounding  tissues. 


STliKPTOCOCCI. 


571 


If  streptococci  are  carried  by  the  bloodstream  into  tlie  coronary  arteries, 
there  are  i)rodnced  in  tlie  heart-muscle  inllammatory  loci,  which  are 
usually  purulent  in  character. 


Fig.  439.— Endocarditis  of  the  wall  of  the  left  auricle,  due  to  streptococci  (alcohol,  methyl-violet,  car- 
mine), a,  Masses  of  cocci;  b,  bj,  leucocytes  and  coagula;  c,  area  of  proliferation;  d,  inflamed  endo- 
cardium.   X  100. 


•"ii^Hi 


■'    ■  •    .    '•"■AT*'..  ■■..    -      "-^.v,      l*"- J     "".• 

■-■■■■■  •:;:^-^#?'=^^*^-^*s 


>;,^  •••»>■.  ■•:..:  ... .  ._ 


im-^ 


Tub.  440.— Erythema  multiforme,  due  to  streptococxus  infection,  arlslnj?  In  the  middle  ear  (Flff.  4^57), 
from  a  child  eiRht  months  old.  Section  through  a  red  spot  in  the  skin  of  the  Imck  of  the  foot  (alcohol, 
methyl-violet,  carmine),    a,  Coriura ;  h,  subcutaneous  tissue  ;  c,  capillaries  Ulled  with  streplwciK'cl.     X  46. 


572 


THE    PATHOGENIC    FISSIOX-FUXGI. 


If  the  cocci  pass  to  a  blood-vessel  of  the  skin  or  subcutaueons  tissue, 
they  may  increase  in  the  same  to  such  an  extent  that  they  form  perfect 
casts  of  the  capillaries  (Fig.  440,  c).  As  the  result  of  the  surrounding 
hyperiemia  there  are  produced  in  the  skin  red  spots  aud  swellings,  and 
eventually  purulent  foci.  In  the  Mdneys,  in  whose  vessels  there  often 
occurs  an  extraordinary  multiplication  of  streptococci  (Fig.  441,  o,  h), 


^|^\>: 


"m 


'h^x^^^-'"*^^ 


Fig.  441.— Extreme  streptococcus  infection  of  the  kidney  fgrayish  areas),  arising  after  streptococcus 
angina  (alcohol,  AVeigerfs  stainj.  a.  Cocci  in  the  intertubular,  h,  in  the  glomeruiar  capillaries  ;  c,  urinary 
tubules ;  d,  flbrin  in  the  urinary  tubules.    X  280. 


there  arise  in  the  first  jDlace  grayish -yellow  circumscribed  areas  of  dis 
coloration,  which  are  dependent  upon  the  collection  of  bacteria,  the  local 
antemia,  tissue- necro.sis,  and  often  a  beginning  serofibrinous  exudatioi 
(d).  Later,  yellow  discolorations  and  softening  of  tissue  appear,  cone 
spouding  to  suppuration.  Similar  changes  may  be  demonstrated  also  ir 
other  organs. 

The  danger  of  a  streptococcus  infection  depends  j^artlj"  upon  the  severt 
progressive  loc(d  changes  aud  the  formation  of  metastases,  and  j^artlj'  upor 
the  accompanying  intoxication,  which  finds  expression  in  the  fever  anc 
the  severe  general  symptoms.  If  the  symptoms  of  intoxication  are  very 
prominent  the  condition  is  designated  septicaemia.  A  predominance  ol 
meta.static  suppuration  leads  to  the  form  of  disease  designated  as  pyae 
mia.  A  coml^ination  of  both  conditions  is  known  as  septicopyaemia  oi 
pyosepthasmia  (of.  ^  11). 

The  course  of  a  streptococcus  infection,  as  well  as  the  mode  of  en 
trance  of  the  cocci  into  the  body,  can  usually  be  recognized,  since  th« 
infection  ordinarily  starts  in  the  injured  outer  skin  or  from  deeply  pene 


STHKPTOCOCCI.  573 

ti-itiiig:  wounds,  from  tlio  imieosa  of  tlio  uiipin-  dijrestive  and  rospiraloiy 
tracts,  or  from  tlu\tiviii1al  a])paratus  as  the  result  of  chanjivs  due  to  (-liild- 
birtli.  Cryptogenic  infection  is,  however,  not  rare;  in  sucli  eases  llu' 
first  synii)toms  reeoiiiii/ahle  or  at  least  noticed  clinically  aiv  those  de- 
l)endeiit  ujx)!!  the  disease  of  an  internal  ory;an,  so  that  it  appeals  as  if 
the  infection  Mas  ])iimai y  in  this  ori;an. 

The  indi\idual  foci  of  disease  in  sti'eptococcns  infection  may  jiresenl 
very  different  degrees  of  severity  of  inflammation  ;  and  this  is  (h'pendent 
])artly  upon  the  virulence  of  the  bacteria,  i)artly  upon  the  in;ii\  idual 
ditferences  of  the  infected  persons,  partly  upon  the  seat  of  the  infection, 
and  ])artly  upon  the  influence  of  precediniioraccom])anyin.<,^  ]>atholof;i('al 
conditions.  As  re<iards  this  last  factor  it  may  be  note(l  thai  many  infec- 
tious diseases  (diphthei-ia,  scarlatina,  smallpox,  t nl)ercnIosis,  tyjdioid 
fever,  influenza)  which  lower  the  body  resistance  increase  tin-  predis- 
position to  streptococcus  infection.  In  the  case  of  the  <ii'o\vth  of  strep- 
tococci upon  the  surface  of  the  endocardium,  the  inflammation  often 
bears  a  very  pronounced  proliferative  character  (Fig.  4.'}0,  d,  r).  In 
hfematogenous  streptococcus-dermatitis  (Fig.  440)  the  process  may  cease 
with  the  formation  of  red  spots.  Phlegmons,  wliich  usually  run  a  rapid 
course  and  lead  in  a  short  time  to  tissue-necrosis  and  sui)puration,  may 
also  have  a  very  chronic  course,  particularly  in  the  neck,  and  are  then 
characterized  by  a  progressive  swelling  and  induration  of  the  affected 
area,  so  that  the  affection  may  be  designated  a  '' irooih'ti  jt/ilrf/mon" 
(Reclus).  Fever  may  be  wholly  absent.  The  process  consists  of  a  pro- 
gressive proliferation  of  granulation  tissue  and  a  new-formation  of  con- 
nective tissue  due  to  streptococci  (or  staphylococci),  while  sui)i)uratiou 
is  absent  or  confined  to  circumscribed  areas. 

The  biological  characteristics  of  the  Streptococcus  pyogenes  are  very  variable,  and 
this  is  well  shown  both  in  its  behavior  as  a  disease-producing  agent  and  in  the  cultures 
of  streptococci  taken  from  different  cases.  Consequently  an  effort  has  been  made  to 
divide  the  streptococci  into  different  species,  and  in  particular  has  the  streptococcus 
which  causes  erysipelas  been  regarded  as  a  distinct  form — the  Streptococcus  er!/si))elatis. 
Further,  according  to  the  jilace  in  which  the  streptococcus  was  found,  it  was  formerly 
customary  to  speak  of  a  Stre]>tococcus  piierpcralis  {Arloiiuj),  Str.  articulorum  (Fliigye). 
Str.  scarlatinosus  (Klein);  or,  according  to  the  manner  of  growth,  of  a  .S^-.  lorrgns  and 
Str.  brevis,  etc.  {von  Lingelsheim).  These  characteristics  are,  however,  not  sufficient  to 
form  a  basis  for  the  separation  of  the  streptococci  into  different  species  ;  ami  it  appears 
more  correct,  or  at  least  more  expedient,  to  consider  all  the  chain-forming  strepococci 
as  one  species,  which  appears  in  many  varieties.  According  to  Howard  and  Perkins 
{J(ur.  of  Med.  Research,  1901)  there  is  a  small  group  of  pathogenic  capsulated  strepto- 
cocci characterized  by  the  viscidity  of  their  growth  and  by  the  formation  of  gelatin- 
ous exudations  in  animals.     For  this  group  they  propose  the  name  of  Streptococcus 


In  diphtheria  and  scarlet  fever,  streptococcus  infections  of  the  throat  and  air-pas*- 
sages  are  extremely  common,  particularly  in  the  case  of  the  first -named,  so  tliat  niany 
authors  {Baumyartcn.  Dalimer)  are  inclined  to  assign  to  the  stre[)tococcus  a  co-ordinate 
position  with  the  diphtheria-])acillus  in  the  causation  of  dii)htheria — the  dii)htheria- 
bacilli  predominating  in  the  lighter  forms  of  infection,  the  streptococci  in  the  more 
severe.  Pure  streptococcus  infections  maj'  present  the  same  picture  as  tliat  produced 
by  the  LoeJJler's  bacillus.  If  both  forms  of  bacteria  are  present,  their  effects  nmy  l)e 
combined;  perhaps  also  the  presence  of  streptococci  increases  the  virulence  of  tlie 
diphtheria-bacilli. 

The  Streptococcus  pyogenes  is  especially  pathogenic  for  mice  and  rabbits  (much 
less  so  for  dogs  and  rats);  but  its  virulence  varies  greatly,  and  rapidlv  decreases  in 
cultures  grown  on  ordinary  media.  Its  virulence  is  retained  for  a  relatively  long  time 
(Murmorek)  in  cultures  of  the  cocci  in  liuiiKin- or  in  liorse-serum  (serum  two  p:irls. 
bouillon  one  part),  or  in  a  mixture  of  Ijouiilon  and  ascitic  fhiid. 

The  nature  of  the  poisons  produced  by  streptococci  is  not  known.  It  has 
been  definitelv  determined  that  filtered  cultures  sterilized  at  0.";-7()°  ('.  contain  poisons; 


574  THE    PATHOGENIC    FISSION-FUNGI. 

but  it  is  not  yet  known  whether  this  poison,  like  the  toxin  of  the  diphtheria-bacilltis, 
produces  an  antitoxin  in  the  organism  and  therefore  should  be  reaardcd  as  a  true  toxin. 

According  to  Simon  there  can  be  distinguished  an  intracellular  weakly  virulent 
poison  and  a  toxin  excreted  by  the  streptococcus.     The  latter,  however,  is  produced  ■ 
only  under  certain  conditions  as,  for  example,  under  the  influence  of  the  bactericidal  ' 
juices  of  the  animal  body.     Under  certain  conditions  the  streptococcus  can  also  pro-ii 
duce  ha^molvsin. 

Numerous  investigators  {Neufdd,  Rimpaii,  Tavel,  Menzer,  Aro7ison,  Marmorek, 
Moser,  and  others)  have  attempted  to  immunize  animals  against  streptococci  and  to 
produce  an  antistreptococcus  serum,  and  the  sera  thus  obtained  have  been  used  in  the 
treatment  of  streptococcus  affections  in  man.  At  the  present  time  it  is  not  possible 
to  judge  as  to  the  therapeutic  value  of  these  piocedures.  One  serum  obtained  from 
immunized  horses,  according  to  the  method  of  Dr.  Aronson,  is  manufactured  in  theij 
chemical  works  at  Actien  (C.  Schering).  According  to  Neufeld  and  Rimpau,  the  serum 
acts  upon  the  bacteria,  changing  them  so  that  they  are  taken  up  by  the  cells. 

A  number  of  writers  regard  a  small  micrococcus  (Diplococcus  rheutnat icus)  as  the 
cause  of  rheumatic  fever  (see  article  by  Poynton,  Osier's  "Modern  Medicine,"  vol.  ii.). 
Cole  and  others  have  shown  that  various  streptococci  produce  experimental  endocarditis 
and  arthritis,  and  they,  therefore,  hold  that  there  is  no  specific  variety  for  this  affec- 
tion. 

Literature. 

(Strejitococcus  Pyogenes. ) 

Babes:  Sur  les  streptocoques.     Ann.  de  I'lnst.  d.  path,  de  Bucarest,  vi.,  1898. 

Bender:   Ueber  den  Erysipelcoccus.     Cbl.  f.  Bakt.,  iv.,  1888  (Lit.). 

Bernard:  Epidemies  de  streptococcic.     Rev.  de  med.,  1901. 

Bonome  at  Bombicci :  Proteine  degli  strep tococchi.     Rif.  Med.,  1899. 

Bordet:   .Serum  antistreptoroccique.     Ann.  de  I'lnst.  Pasteur,  1897. 

Brunner:   Die  Bcgriffe  Pyiimie  u.  Septhiimie,  Frau.cnfeld,  1899. 

Bumm:  Die  puerperalc  Wundinfection.     Cbl.  f.  Bakt.,  ii.,  1887. 

Chiari:  Holzphlegmone.     Beitr.  z.  Dermat.,  Festschr.  f.  Neumann,  Wien,  1900. 

Dahmer:   Streptokokken  bei  Diphtherie.     Arb.  her.  v.  Baumgarten,  ii.,  1896. 

Dennig:  Septische  Infection.     Mimch.  med.  Woch.,  1897. 

Denys:  Trav.  exec.  s\ir  le  strentocoque  pyog.     Cbl.  f.  Bakt.,  xxiv.,  1898. 

V.  Dungern:    Mischinfection  bei  Diphtherie.     Beitr.  v.  Ziegler,  xxi.,  1897. 

Escherich:  Erfolge  der  Serumbehandlung  bei  Scharlach.     Wien.  klin.  Woch.,  1903. 

Eehleisen:  Deutsch.  Zeitschr.  f.  Chir.,  xvi.;  Die  Aetiologie  des  Erysipels,  Berlin,  1883. 

Erankel,  E.:   Identitat  d.  Streptococcus    pyog.    u.    Streptoc.  erysipelatis.     Cbl.  f. 

Bakt.,  vi.,   1889. 
Guarnieri:  Contrib.  alio  studio  dello  streptococco  dell'  eresipela.     Arch.  p.  le    Sc. 

Med.,  xi.,  1887. 
Hajek:  Ueb.  d.  atiol.  Verhaltniss  d.  Erysipels  zur  Phlegmone.     Wien.  Med.   Jahrb., 

1887. 
Hoffa:  Ervsipelkokken  b.  einer  Kniegelenksentziindimg  nach  Erysipel.     F.  d.  Med., 
iv.,    1880. 

Homen:  Die  Wirkung  d.  Streptokokken  u.  ihre  Toxine.     Beitr.  v.  Ziegler,  xxv.,  1899. 

Howard  and  Perkins:   Streptococcus  mucosus.     Jour,  of  Med.  Res.,  1901. 

Janowski:   Die  Unsachen  der  Eiterung.     Beitr.  v.  Ziegler,  xv.,  1894  (Lit.). 

Jochmann:  Bakterienbefunde  bei  Scharlach,  Breslau,  1904. 

Jordan:    Die  .U'tiologie  des  Erysipels.     Arch.  f.  klin.  Chir.,  42  Bd.,  1891. 

V.  Kahlden;  \'erhaltn.  d.  Bakteriolog.  z.  Chirurg.     Cbl.  f.  Bakt.,  i.,    18S7;    Sepsis.! 
i;ulciihurg's  Pvoalencyklop.,  1899;   Septikamie.     Cbl.  f.  a.  P..  1902. 

Koch.:  V\'undinf('c(ionskrankheiten,  Leipzig,  1878. 

Koch  u.  Petruschky:    Erysipelimpfungen.     Zeit.  f.  Hyg.,  xxiii.,  189G. 

Krause:    llolzart.  llntziind.  d.  Bindogewclies.     Cbl.  f.  Chir.,  1899. 

Kurth:   rntcM-sclioidung  der  Streptokokken.     Arb.  a.  d.  K.  Cesundheitsamt,  vii.,  1891, 

Kusnetzoff:    lI<)lzi)hl('gmone.     Arch.  f.  klin.  Chir.,  58  Bd.,  1899. 

Laitinen:  Sircptococcustoxin.     Cl)l.  f.  allg.  Path.,  vii.,  1896. 

Lemoine.  Angines  non  diphtheriijues.     Ann.  de  I'lnst.  Pastern",  ix.,  1895. 

Lenhartz:    Die  septischen  Erkrankungen,  Wien,  1903. 

V.  Lingelsheim:  Eigenschaften  versch.  Streptokokken.    Zeit.  f.  Hyg.,x.,  1891;  Strep-; 
tokokken.     Ilandb.  d.  path.  Org.,  iii.,  .Jena,  1903. 

Eongcope:   Streptococcus  mucosus  (Howard).     Jour,  of  Med.  Res.,  1902. 

Eubai'sch:   Streptokokkengruppe.     Ergebn.  d.  allg.  Path.,  iii.,  1897. 

de  Marbaix:  VA.  sur  la  virulence  des  streptocoques.     La  Cellule,  viii.,  1892. 


DIPLOCOCCrS    PNEUMOXI,T<..  575 

Marmorek:  Versuch  cinor  Thoorie  dor  septischon  Krankhcitcn,  Stuttcjart,  1S9  I. 
Menzer:    Das  Antistreptokokkeiisoruni.      I).  iiumI.  Wodi.,  l<K);i. 

Neufeld:    Inmumitat  u.  AL-.irhniiuition  ht-i  Strcptokokkcii.     Z.  f.  liyp..  -M  H.I..    I'.to:',. 
Neufeld  u.  Rimpau:   AntikorpiT.  d.  Streptokokkeniiiiimmoscruins."    J),  incd.  WOc-li., 

1904. 
V.  Noorden:    Streptokokkeu  iin  Blut  boi  Krysipolas.     Miincli.  mod.  Wucli.,  1SS7. 
Pasquale:  Veii^k'icli.  Unters.  iihcr  Streptokokken.     Beitr.  v.  Ziegler,  xii.,  IS'.Ki. 
Pawlowsky:  Aetiokigie  der  acuten  Peritonitis.   Cbl.  f.  Chir.,  1SS7;   l'el)er  die  Mikro- 

orjianisiuen  ck>s  Krysipels.     Berk  klin.  Woch.,  18SS. 
Petruschky:    I'eher  die  Specifitat  des  Erysipel-Streptococcus.     Zcit.  f.  llv;,'..  x.xiii., 

lS9t). 
Recliis:   Plik'siinone  ligneux  du  cou.     Rev.  de  Cliir.,  ISOCk 

Rog-er:    Coiitr.  a  I'et.  exp.  du  streptococpie  de  I'erysipele.     Rev.  de  meek,  1S92,  1890. 
Rosenbach:    Die  Mikroorganismeii  der  Wundinfectionskrankheiten,  W-'esbaden,  1884. 
Simon:   C.ifte  der  Slrcptokokken.     Clik  f.  Bakt.  Orfr.,  xxxv.,  1902. 
Singer:    Aetiok:>cie  u.  Klinik  d.  acuten  (lelenkrheuniati.snius,  Wien,  1897. 
Tavel:   Polyvalentes  Streptokokkenseruin.     D.  nied.  Woch.,  190;k 
Vossius:   .Streptokokkenembolie  em  Autre.     Zeit.  f.  CJebh.,  xviii.,  1S90. 
Weaver:    The  \'itahty  of  Bacteria  from  the  Throats  of  Scarlet-Fever  Patients,  with 

Si^ecial  Study  of  Streptococci.     Jour,  of  Med.  Res.,  HtOli. 
Weiss:   Aetiologie  d.  Otitis  Media  im  Siiuglingsaltcr.     Beitr.  v.  Ziegk-r,  xxvii.,  1900. 

§  158.  The  Diplococcus  pneumonise  (Fijinkcl,  \\'('icliscll)auiii  i,  or 
Streptococcus  lanceolatus  ( (ninialeiu),  or  Diplococcus  lanceolatus  i  I'(»a. 
Uunluni-Ulfivdiizzi),  and  also  known  as  tlie  riwionococcn.s,  is  a  i>atlioj;«'ni(' 
Streptococcus  of  very  frequent  occurrence.  It  forms  spherical,  oval,  and 
lanceolate  cocci  (Fig.  442,  a),  which  in  the  human  body  are  usually  sur- 
rounded by  a  transparent  cai^sule,  and  are  grouped  together  in  pairs  (b, 
d),  or  more  rarely  iu  chains  of  such  pairs  (c),  or  in  large  colonies  ((/). 

The  Diplococcus  pneumonine  stains  well  with  fuchsin  and  with  gentian 
violet,  aud  by  these  stains  the  capsule  maybe  demons!  laled  in  smeai- 

preparations.     The    cocci    are  also    stained    l)y 

Gram's  method. 

The   cocci    are   facultative   anaerobes.     They 

will  not  grow  upon  gelatin  at  ordinary  room- 
&  ®  (^  ^  ^~®^  temperature,  but  do  so  upon  slightly  alkalint^ 
^n^fi  V  n  "^^  blood-serum-gelatin,  upon  agar  and  in  bouillon, 
^\*     ///    ^Sis       at  a  temperature  above  22°  C,  and  best  at   the 

temperature  of  the  boih'.  They  form  upon  the 
m^^i^l^^^Z:  surface  of  the  medium"  a  delicate,  IranslucMit, 
SaTcl'rb.eTo^rwi(i  A-listening  culture,  which  sngge.st.s  the  dewlikr 
a Keiatiiioiis capsule ;  c,cimin  deposit  01  luoisture  upou  a  co\  er-gUiss  ( I'  rankel  )  ; 
onyXS^'x  m*' '''  '"'■      and  consists  of  diplococci  and  chain-cocci  without 

capsules.  The  growth  is,  however,  scanty;  and 
easily  dies  out.     Upon  potatoes  the  cultures  do  not  thrive. 

The  Diplococcus  pneumonije  is  in  a  great  number  of  cas<'s  (according 
to  Weichselbaum  in  seventy-one  per  cent.)  the  cause  of  liir  allVdion  ol 
the  lung  known  as  crovpoiifi p)ieiiinoiii<i,  in  wliich  the  lung  is  the  .seal  ol'  an 
acute  intiammation  wliich  is  ushered  in  l>y  a  (-((ngesl  iv<'  hypfia-mia  (  Fig. 
443,  a ).  Ill  the  cour.se  of  the  disea.sc;  the  alveoli  over  large  areas  of  the 
lung  become  filled  with  a  coagulated  exudate  consisting  of  desipiamated 
epithelium,  leucocytes,  red  blood-cells,  serous  lliiid  and  librin  (  Fig.  2<»0- 
Iu  the  normal  course  of  thedisea.se  the  exudate  becomes  li<|iieli«Ml  and 
absorbed.  As  has  been  sliown  by  numercms  observations,  the  Dijdococ- 
cus  pneumoniae  may  also  cause  in  the  lungs  other  inllanimaloiy  pi-oc('S.ses 
bearing  the  chaiacter  of  a  catarrhal  or  croupous  broiulioitiirmiionia. 
During  the  course  of  the  disease  the  cocci  are  found  especially  in  Ihe 
inflamed  areas,  in  the  greatest  nuiiii)eis  at  the  beginning  of  the  inllam- 
mation;  they  lie  in  pait  free  in  the  alveoli  ^^/>)  and  in  part  clinging  to 


576 


THE   PATHOGENIC   FISSION-FUNGI. 


cells  (d).  Tliey  are  found  also  in  parts  of  the  lung  bordering;  upon  the 
inflamed  area,  in  the  pleura,  and  under  certain  conditions  also  in  the  peri- 
cardium, peritoneum,  meninges,  accessory  nasal  cavities,  cellular  tissue 
of  the  neck,  in  the  mediastinum,  sulnnucosa  of  the  soft  palate  and 
pharynx,  in  the  conjunctiva,  and  the  skin.  In  all  these  places  they  may 
give  rise  to  inflammatory  changes.  At  times  they  may  be  demonstrated 
in  the  juice  of  the  spleen,  and  in  the  blood,  and  in  pregnant  women  may 
pass  into  the  ftetus  (Viti).  Under  certain  circumstances  they  may  be 
wideh/  distributed  througlwtd  the  hodt/;  and  may  cause,  in  the  meninges, 
pleurte,  x^ericardium,  and  peritoneum,  librinous,  serofibi-inous,  and 
at  times  seropurulent  and  fibrinopurulent  inflammations,  without  giv- 
ing rise  to  a  pneumonia.     Further,  they  may  cause  inflammations  of 


Fig.  443.— Diplococcus  pneumonia  in  early  stage  (formalin,  fiiclisjn).    a.  HvpiTipinic  vosspls;  7>.  (iiplococci; 
c,  cellular  exudate ;  d,  swollen  epithelial  cells  covfred  w  itli  (■<ir<l.      ■.  M\. 

the  conjunctiva,  middle  ear,  endocardium,  kidneys,  joints,  tubes,  endo- 
metrium, ])arotid,  thyroid,  bone-marrow,  and  periosteum,  and  these  in- 
flammations juay  lead  to  suppuration.  In  many  cases  the  mouth  and 
nasopharynx  ai)pear  to  be  the  avenue  of  entrance — in  these  regions  the 
cocci  are  not  infrequently  found,  even  in  healthy  individuals.  Corre- 
spondingly, in  cerebral  and  cerebrospinal  meningitis  (  Weichselbaum)  the 
maxillary  cavities,  tympanic  cavity,  and  the  ethmoid  labyrinth  often 
contain  exudates  with  diplococci.  They  are  found  in  the  exudates  in  all 
the  forms  above  mentioned ;  and  the  gelatinous  capsule  nuiy  present  a 
very  variable  thickness. 

When  inoculated  into  rabbits,  guinea-pi2;s,  and  mice,  the  Diplococcus  pneumoniae 
increases  in  the  form  of  encapsulated  cocci,  particularly  in  the  blood  and  serous  cavities, 
and  may  cause  pneumonia  with  bloody  serous  exudate.     ^Vhen  injected  beneath  the 


PNEU-MOCOCCl'S    AM)    MENINGOCOCCUS.  5/7 

skin  of  the  rabbit's  ear  (Xcufeld)  they  also  produce  erysipelatous  inflainniatioiis. 
Rabbits  are  especially  susceptilile,  as  they  die  with  symptoms  of  septiciemia  in  from 
thirty-six  to  forty-eight  hours  after  subcutaneous  inoculation.  The  injection  of 
j)ure  cultvu'es  into  the  pleural  cavity  of  ral)bits  gives  rise  to  a  |)leuritis  as  well  as  a 
spleni/.ation  of  the  lung,  in  which  the  paicnchyma  of  the  organ  is  filled  with  a  hiemor- 
rliacic  serous  exudate. 

According  to  .1.  Frunkel  the  cocci  verj'-  easily  lose  tlicir  virulence,  jiarticularly 
when  cultivated  upon  milk;  and  if  it  is  desired  to  retain  their  virulence  they  must, 
from  time  to  time,  be  ])assed  through  susceptible  animals.  Cultivation  of  the  cocci  at 
42°  C.  for  one  to  two  days  destroys  their  virulence. 

'There  still  exist  different  views  as  to  the  role  which  the  Diplococcus  vneumoniiv 
phn/s  in  meningitis.  According  to  the  investigations  of  Wcirltselbauin,  Jaec/er,  Foa, 
Alhrccht  and  Ghon,  Councilman.  Malhn-i/  and  U ';(';////,  ami  others,  it  may  lie  regariled  as 
definitely  demonstrated  that  the  Diplococcus  pncinnonur  can  aluo  cause  mcnlnffitls,  and 
that  there  exists  also  a  coccus,  the  Diplococcus  intracellularis  meningitidis 
[Welchselbaiim),  which  is  different  from  the  pneumococcus  ami  is  to  l>e  reganlcd  as  the 
cause  of  epidemic  cerebrosplnol  menincjitis.  According  to  dacijir,  tliis  organism  does 
not  grow  like  the  streptococci,  but  forms  hea[)s  like  the  staphylococci.  Albrccht, 
Ghon.  and  Welchselbaum  point  out  its  great  similarity  to  the  gonococcus.  They  propose 
to  call  it  in  the  future  the  Micrococcus  meningitidis  cerebrospinalis.  It  is  found 
in  the  nasal  secretions  of  cases  of  epidemic  Uicningitis  and  also  in  that  of  individuals 
corning  into  contact  with  such  cases.  In  the  inflammatory  cereiirospinal  exudate  it  is 
found  particularly  in  the  polyniiclear  leucocytes.  The  essential  pathological  lesions  are 
inflammatory  changes  in  the  membranes  of  the  cord  and  brain,  and  in  the  tissue  of  the 
brain,  cord,  and  nerves.  Flexner  and  Jobllng  (Jour.  Amcr.  Med.  Assoc,  July, 
190S)  re]iort  most  encoiu'aging  results  in  the  treatment  of  epidemic  meningitis  with 
a  .serum  pi-epared  in  the  horse  liy  inoculation  of  Diploaiccits  Intracellularis. 

Pneumotoxin  is  formed  by  the  pneiunococci  most  al)undantly  in  the  human  and 
animal  organism,  but  only  sparsely  in  ordinary  nutritive  media  (Isaejf).  It  is  doubtful 
whether  bactericidal  antibodies  or  antitoxins  arise  during  the  course  of  the  disease. 
It  is  therefore  probable  that  the  pneumotoxin  does  not  belong  to  the  true  toxins. 
Animals  may  be  Immunized  in  various  ways  against  pneumococci,  and  the  serum 
of  an  immunized  animal  may  be  used  also  as  a  healing  serum.  The  results  of  treat- 
ment in  man  are  still  doubtful.  Difficulties  arise  through  the  fact  that  jineunionia 
can  be  caused  also  by  various  other  bacteria  (pneumo-bacilli,  i)us  cocci,  influenza- 
bacilli,  etc.).     (See  r.  Marikovsky  and  Oppenhelmer,  I.  c.) 

Literature. 

(PneionocoecH.s  ait<l  Jlmiiif/oeorcus. ) 

Albrecht  u.  Ghon:  Meningococcus  intracellularis.  Cbl.  f.  Bakt.,  Orig.,  xxxiii.,  1903. 
Banti:  Contrib.  alio  studio  degli  pneumococchi.     Lo  Sperimentale,  ISSfi:    Sull'  eti- 

ologia  della  pneumonite  acuta.     lb.,  1890;   Aetiologie  der  Endocarditis.     Deut.. 

med.  Woch.,  1888;   Localisazzioni  extrapolmonari  del  diplococco  lanceolato.   Arch. 

di  Anat.,  v.,  Firenze,  1891. 
Councilman,    Mallory,  and  Wright:    Epidemic  Cerebrospinal  Meningitis,  Boston. 

1898. 
Emmerich:  Infection  u.  Imnnmisirung  bei  crou]).  rneuiiiDuic.     Zcit.  f.  llyg.,xvii, 

1894. 
Faulhaber:    Bakterien  in  d.  Nieren  l)ei  acut.  Infectionskrankliciten.     Beit.  v.  Ziegler, 

X..   1891. 
Flexner:  Antimeningitis  .serum.  Jour,  of  Exper.  Me(l,.  19()S. 
Foa:   Sulla  infez.  del.  diplococco  lanceolato.     Arch.  p.  le  Sc.  Med.,  xvii.;  Zeit.  f.  llyg., 

xvi.,  189:i. 
Foau.  Bordoni-TJffreduzzi:   Bakterienbefvmde  bei  Meningitis  cerebrospinalis.    Deut. 

med.   Woch..   ]S8(3,    Aetiologie  d.  Meningitis  cerebrospinalis  ej)idemica.     Zeit.  f. 

Hvti.,  iv.,  18S8. 
Frankel,  A.  :   Verb.  d.  med.  Congresses,  "Wiesbaden,  1884.   Zeit.  f.  klin.  Med.,  x.,  xi.; 

Deut.  med.  Woch.,  1886. 
Gabbi:    SuU'  artrite  sperimentale  da  viro  pneumonico.     I.o  Sperimentale.  l.S9(). 
Gamalea'i:  Sur  I'etiologie  de  la  i)nemjionie  fii)rineuse.     Ann.  de  I'lnst.  Pasteur,  ii.,  188S. 
Haegler:   Die  pyogenen  Eigenschaften  von  Pneumokokken.     Fortschr.  d.  .Med.,  viii., 

1890. 
Hauser.  Pneumoniekokken  bei  Meningitis  cerebrospinalis.     Miinch.  nied,  \\()ch.,1888. 
Herrick:  Pneumococcic  Arthritis.     Amer.  Jour,  of  Med.  Sc,  1902. 

37 


578 


THE    PATHOGENIC    FISSION-FUNGI. 


Jager:   Aetiol.  d.  ^leningitis  cerebrospin.  epidemica.     Zeit.  f.  Hyg.,  xix.,  1896;  Deut. 

med.  Woch.,  1899;    Die  Cerebrospinalmeningitis  als  Heeresseuche,  Berlin,  1901; 

Meningococcus   intra cellularis.     Cbl.    f.    Bakt.    Oriei:.,   xxxiii.,    1903;     Spezifische 

Ajrdutination  der  .Meningokokken.  Z.  f.  Hyg.,  44  Bd.,  1903.  ' 
Janowsky:  Trsachen  der  Eiterung.  Beitr.  v.  Ziegler,  xv.,  1894. 
Koch:    :\Iittlieil.  a.  d.  K.  Geaundheitsamte,  Berlin,  1881. 

Kruse  u.  Pansini:   Unters.  lib.  Diplococcus  pneum.     Zeit.  f.  Hyg.,  xi.,  1892. 
Lengemann:  Verh.  d.  Leukocyten  bei  Pneumokokkeninfektion.     B.v.  Ziegler,  xxix., 

1901. 
Macaigne  et  Chipault:  Arthrites  a  pneumocoques.     Revue  de  med.,  1891. 
V,    Marikovsky :    Die  Serumtherapie  der  Pneumonie.     Cbl.  f.  Bakt.  Ref.,  xxxiv.  190^ 

(Lit.). 
Netter :  Rech.  bacteriologiques  sur  les  otites  moyennes  aigues.     Cl)l.  f.  Bakt..  v.,  18<S9; 

Le  pneumocoque.     Arch,  de  med.  exp.,  ii.,  1890. 
Neiifeld:  Erzeugung  v.  Erysipel  am  Kaninchenohr   (lurch   Pneumokokken.     Zeit.  f. 

Hyg.,  36  Bd.,  1901. 
Nikiforoff:  Ueb.  e.  dem  Pneumococcus  ahnlichen  Mikroorganisnius.     Zeit.   f.    Hyg., 

viii.,  1890. 
Oppenheimer:   Toxine  u.  Antitoxine,  Jena,  1904. 

Ortmann :  Aetioiogie  d.  acuten  Cerebrospinalmeningitis.    Arch,  f .  e.xp.  Path. ,  xxiv.,  1888. 
Ortmann  u.  Samter:  Localisation  d.  Diplococcus    pneumoniae.     Virch.    Arch.,   120 

Bd..  1890. 
Schabad:  Allgemeine  Pneimiokokkeninfection.     CI5I.  f.  Bakt.,  xix.,  1896  CLit."). 


Fig.  444.— Multiple  ahsf«sses  of  the  skin,  due  to  staphylococci  (alcohol,  <;niniiii',  diain 
of  three  week.s.    a.  Epithelium;  b,  coriuiti ;  c,  hair-follicle;  (I,  c,  purulent  foci  with  - 


tliod).    Child 
X  40. 


Thue:  Pleuritis  u.  Pericarditis  bei  der  crouposen  Pneumonie.     Cbl.  f.  Bakt.,  v., .1889. 

Tizzoni  e  Panichi:  Vaccinazione  contra  il  Pneumococco.    Bologna  R.  Accad.,  ,1903. 

Wandel:    Pseumokokkenlokalisationen.     D.  A.  f.  klin.  Med.,  78  Bd.,  1&03. 

"Weichselbaum :  Aetioiogie  der  acuten  Lungen-  und  Rippenfellentziindungen.  Med. 
Jahrb.,  Wien,  1886;  Histor.  Bericht  iib.  die  Aetioiogie  der  acuten  Lungen-  und 
Rippenfellentzundungen.  Cbl.  f.  Bakt.,  i.,  1887;  Aetioiogie  d.  acuten  Meningitis 
cerebrospinalis.  Fortschr.  d.  Med.,  v.,  1887;  Aetioiogie  u.  path.  Anatomie  der 
Endocarditis.  Beitr.  v.  Ziegler,  iv.,  1888:  Seltenere  Localisation  des  pneu- 
monischen  Virus.  Wien.  klin.  Woch.,  1888;  Der  Diplococcus  jjneumoniffl  als 
Ursachc  der  ])rim:iren  acuten  Peritonitis.  Cbl.  f.  Bakt.,  v.,  1889;  Diplococcus 
IHieum.  u.  Meningokokken.     Handb.  d.  path.  Mikroorg.,  iii.,  1903. 

"Williamson:  Verh.  d.  Pneuniokokkenerkrankung  der  Kaninchen.  Beitr.  x.  Ziegler, 
xxix.,   1901. 

Zau^l:  Acute  Mittelohrentziindimg.     Prag.  med.  Woch.,  1889. 

^  154.  T]m  Staphylococcus  pyogenes  aureus  (Koseubaeh)  or  Micro- 
coccus pyogenes  (Lcluiianii)  consists  of  spliorifal  cells  occuiTiug  singly 


STAPHYLOCOCCI  S. 


.)7«t 


lion  foi- 

iiiiiii' .urniM'-liko  cliish 

IS  mikI 

led  by  \ 

irioiis  iiniliiH'  dyes,  ;u 

.1   mIso 

<Ml]1;iii\( 

Miiacrolx'S,  Itiil    i;ro\s 

licllcr 

or  in  ]>airs.  niid  by  tlieir  iniiltipli 
swaiins.      Tlie  cocci  aiv  easily  si; 
by  Griinrs  iiiclhod.     Tliey  are 
wiuMi  sii])plicd  Avith  oxyuvii. 

The  staphyloeoccns  llirives  on  all  cuUure-niedia,  even  al  ordinary 
rooiu-tenipeialnres,  Uioui;h  belter  at  37"  C.  It  forms  Avliilc  colonies, 
which  inoduce  pii;ineiit  in  those  ])ails  exi)osed  to  the  air  and  become 
oraiiL^c-yellow.  Th«^  i)i.t;iiieiit  rorniatioii  is  most  marked  on  ai;ar  and 
potatoes.  CJelatin  is  slowly  li([Ueiied.  In  the  ])resence  of  j;rape  snjiar 
it  forms  lactic  acid,  acetic  acid,  and  valerianic  acid.  In  bonilion-cnlt 
iires  tliere  are  produced  poisons  of  very  violent  action.  'I'he  Staphylo- 
coccus pyogenes  is  one  of  the  most  frecjuently  occurring  palhogenic  bac- 
teria, and  is,  \vith  the  Streptococcus  i)yogenes,  the  most  common  cause  of 
suppuration.  Both  forms  of  cocci  are  theiefore  designated  pus-cocci, 
in  the  uanower  sense  of  the  term.  It  is  widely  distributed  thioiighout 
the  external  world,  and  has  beeu  demonstrated  in  milk,  wash-water,  and 
waste- water,  as  well  as  iu  the  air  of  operating-rooms  and  sick-cliamlM>is. 


;-.Y) 


Fig.  445.-Miliary  puruleut  nephritis,  caused  by  stiiphylococci,  primary  fiH'iis  in  skin  ifnniiiriil..si.s>  (aln 
hoi,  inetliyl-violet, carmine).    «, Normal  kldnc^y  tissue ;  /*,  collections  of  cfHTi ;  c,  ptinilent  focus.     <4d. 


Increasing  in  the  tissues  of  the  liumaii  body  (Figs.  444-440)  it  causes 
Ussue-def/enerations  and  <is'.s-we-«cY'ro.sY'.s- followed  l)y  ittjUttnmaliou  (I^'igs.  444. 
d,  e;  445,  h,  c ;  446,  c,  d),  which  is  usually  puruleut  in  chardcUr,  but  not 
infrequently  is  less  severe — that  is,  it  dors  not  lend  to  ti.ssuf-.si())pi(r<itioii. 

The  SKjypu rations  ])rodu(;ed  by  staphylococci  ai-e  usually  rirfuuisrriltrd 
(Figs.  444,  445),  and  show  a  less  tendency  to  involve  rapidly  the  sur- 
rounding tissue  than  do  the  suppurations  caused  by  streploc<tcci.  In  the 
skin  they  give  rise  iu  particular  to  the  forms  of  iiillaimnaliou  known  as 


5S0 


THE   PATHOGEXIC    FISSIOX-FUXGI, 


acne,  eczema,  furuncle,  aud  cutaneous  aud  subcutaneous  ahscesses.  In  the 
osseous  system  thej^  are  the  most  frequent  cause  of  the  hematogenous 
purulent  diseases  of  the  bone  marrow  and  periosteum  known  as  septic 
o.sfro)n!/f'Iifis  (Fig.  446)  and  jyeriostUis.  They  not  infrequently  cause  ^w>-?^- 
Jent  iujtannnations  of  the  liver,  Junr/s,  pleura,  peritoneum,  brain,  meninges, 
muscle,  mj/ocardium,  spleen,  hidneijs,  joints,  etc.  ;  and  are  often  the  cause  of 
severe,  iu  part  purulent,  inf animations  of  the  endocardium.  Since  the 
\  irulence  of  the  staphylococci  varies,  they  can  also  produce,  in  all  the 
regions  named,  lighter  transitory  inflammations  which  heal  with  or  without 
scar-formation. 

The  portal  of  entrance  of  staphylococci  is  often  easily  recognizable 
(especially  in  the  case  of  wounds),  and  the  same  is  true  of  the  path  of 


Fig.  446. — Staphylococcus  osteomyelitis  of  calcaneus.     (Alcohol, 
l'ral)eculae   of  bone;    b,  fatty  marrow;   c,  purulent  area;    d,  cocci. 


methvl    violet,    carmine.);) 

C    100."  |! 

the  metastasis  to  the  internal  organs,  whereby  inflammations  of  the  tymjyh-i 
vessels  (lymph  an  go  it  is)  and  of  the  blood -vessels  (phlebitis,  arteritis)  make 
their  ;)pi)oaraiu'i'.  Cryptogenic  infections  aie,  however,  of  not  infre- 
(|uent  occurrence,  so  that  the  hrst  recognizable  localization  of  the  infec- 
tion appears  in  the  endocardium,  myocardium,  or  bone-marrow.  The 
spread  of  sta])hylococci  through  the  blood-stream  leads  to  multiple  locali- 
zation with  abscess  formation,  and  this  condition  is  designated  pyasmia,! 
as  in  the  case  of  the  similar  condition  caused  by  the  streptococcus.  The 
com]dication  of  a  stai)hylococcus  infection  with  severe  symptoms  of 
intoxication  is  also  known  as  septicaemia  ;  and  the  combination  of  a 
stai)liylococcus-pv?emia  with  septicnemia  is  also  known  assepticopyasmia 
(cf.  ij  11). 

The  Staphylococcus  pyogenes  aureus  is  also  pathogenic  for  animals:  horse, 
dog,  cattle,   goat,  sheep,  rabbit,  guinea-pig,  and  mouse,  particularly  fori 


STATl  1  WAXJOCCA  S.  581 

the  first-named,  less  so  for  the  last.  In  these  animals  it  canses  suppu- 
ration. The  staphylococens  los«'s  its  virnleuee  t'asily  in  cultuics.  'Ilu- 
inoculation  of  cultures  of  hi.^li  \  irukMice  into  susccpt il)l('  miinials  causes 
a  gchilinous  anlema. 

Closely  related  to  the  Staphylococcus  l)yo^('Iles  aniens  aic  the  Staphy- 
lococcus pyogenes  albus  ( I^.senbach  i  and  tiie  Staphylococcus  pyogenes 
citreus  (  Passet ) ;  these  forms  jn-ohably  icpicsent  modilied  \  :iiielies  of 
the  aureus.  The  albus  forms  whit isii,  Uw  rilnx.s  Icnuni  yellow  colonies. 
These  bacteria  occur  in  the  same  legions  and  ]»ro(luce  the  same  effects  as 
the  anreus,  but  are  more  rare  than  the  last  nanu'd. 

The  Staphylocoecns  pyog:enes  aureus  usually  occurs  alone  in  the  pus- 
foci,  bnt  not  infrequently  there  may  be  associated  with  it  otiier  pus- 
cocci  or  even  bacilli,  as,  lor  example,  the  Bacterium  coli  commune,  or 
the  typhoid-bacillns. 

The  staphylococcus  forms  a  hsemolysin  and  a  leukocidin  (Van  drr  Veltir,  Xeisi^rr, 
and  Wechsbera)  which  destroys  the  leucocytes  of  rabbits,  and  also  poisons  wliich  have 
a  degenerative  action  vipon  the  tissues.  The  bodies  of  dead  staphylococci  cause  iii- 
•  flammaticn  \\  hen  injected  into  the  tissues.  Staphylolysin  and  hannolysin  and  leukoci- 
din form  in  the  organism  antistaphylolysin  and  antUeukocidin  and  therefore  belong  to 
the  toxins. 

A  serum  produced  by  pathogenic  staphylococci  will  agglutinate  both  the  homol- 
ogous strain  as  well  as  the  majority  of  other  pathogenic  strains  {Kloppstock  and  Bockcn- 
heimer). 

Literature. 

{Staph  i/Joeoccus  Pyoyenrs  An  mis.) 

Babes:  Bakt.  Unters.  iib.  septische  Processe  im  Kindesalter,  Leipzis,  1SS9. 
Bockhart:  Aetiol.  d.  Impetigo,  d.  Furunkels  u.  d.  Sykosis.     Monatsh.  f.  pr.  Dermat., 

1887. 
Bonome:   Staphylocoques  pyogenes.     Arch.  ital.  de  Biol.,  viii.,  1887. 
de  Christmas:   Rech.  exper.  sur  la  suppuration.     Ann.  de  ITnst.  Pasteur,  ii.,  1888. 
Dennig:    Ueber  septische  Erkrankungen,  lieipzig,  1891. 
Escherich:  Staphylokokken  in  Hautabscessen  v.  Sauglingen.     Miinch.  moil.  Woch.. 

1886. 
Garre:   Zur  Aetiologie  der  acuten  eiterigen  Entziindung.     Fortschr.  d.  .Med.,  ill.,  188,"). 
Hessler:   Die  otogene  Pyamie,  Jena,  1896. 
Hohnfeldt:  Histogenese  d.  durch  Staphylococcus  hervorger.  Abscesse.     Pelt  r.  v.  Zieg- 

ler,  iii.,  1888. 
Janowski:   Die  Ursachen  der  Eiterung.     Beitr.  v.  Ziegler,  xv..  1894  (Lit.). 
Jiirgensen:    Kryptogenetische  Septikopyiimie.     Lebrb.  d.  spec.  Patii..  Leipzig,  IS!) J. 
V.  Kahlden:   Sepsis.     Kulenburg's  Realencykloji.,  1899. 
Kloppstock  u.   Bockenheimer:  Agglutination     der   Staphylokokken.     A.     f.    kiin. 

Chir.,  72  Bd..  1904. 
Koch:   Die  Wundinfectionskrankheiten,  Leipzig,  1878. 

Kocher:   Osteomyelitis,  Periostitis.  Strumitis.     Langenlieck's  Arch.,  wiii.,  1879. 
Kraske:  Aetiologie  d.  acuten  Osteomyelitis.     Verb.  d.  XV.  Chir.-Coiigr.,  Berlin,  I.SSC). 
Krause:    Mikrokokken  der  infectio.sen  Osteomyelitis.     Fort.schr.  d.  .Med.,  ii..  issj. 
Lenhartz:   Die  septischen  Erkrankuniren,  Wien,  1904. 
Lubbert:   Der  St;iphylococcus  pyogenes  aureus,  Wiirzl)iirg,  ISSCi. 
Neisser  u.  Lipstein:'  Die   Staphylokokken.     llandh.  d.    patli.  .Mikroorg.,  iii.,  Jena, 

1903   (Lit.). 
Neumann:  Micrococcus  jiyoe.  tenuis  u.  Pneunioniecoccus.     ('l)l.  f.  Pakt.,  vii.,  1.S90. 
Ogston:    .Micnjcoccus  Poisoning.     Journ.  of  Anat.  and  Phys.,  xvi.,  xvii,,  1.SS2. 
Oppenheimer:    Staphylolysin  u.  J.eukocidin.     JIandb.  d.  p.ath.   Mikroorg.,  iii.,   190.!. 
Petruschky:    Infection  mit  pyogeiien  Kokken.     Zeit.  f,  Ilyg.,  xvii.,  1S!M. 
Ribbert:    Experiment.  Myo-  vi.  Endocarditis.     Fort.schr.  d.  .Med.,  iv.,  JSSC;    Vcrl:iuf 

der  durch  Staphylococcus  in  d,  Jlaut  y.  Kaninchen  liervonrerMfenen  Ijitziindiin- 

gen.     Deut.  ined.  Woch.,  1889;    Die  patholog.  Anat.  u.  die  lleihiiig  der  durch  d. 

Staphylococcus  pyog.  aureus  hervorger.  Veriinderungen,  Bonn,  1891. 


582 


THE    PATHOGEXIC    FISSION-FUNGI. 


Rodet  et  Courmont:  Subst.  toxiques  elali.  par  le   staphyloc.  pyog.     Rev.  dp  mt'd., 

xiii..  lS(t:3. 
Rosenbach:    Mikroorganismen  d.  Wundinfectionskrankh.,  "Wiesbaden,  1.SS4. 
Sahli:     Aeticl.   d.   Gelenkrheumatismus   (Staph,   eitreus).     Corr.   f.   Schweiz.  A<:'rate, 

Scholtz:    Paras.  Natur  d.  Ekzems.     Deut.  med.  Woch.,  ]9'J0. 
Singer:   Aelioiogie  u.  klin.  d.  aciiten  Gelenkrheumatisirms,  Wien,  1897. 
Steinhaus:    Aetiologie  d.  Eiterung.     Zeit.  f.  Hyg.,  v.,  1888. 

Struck  11.  Becker:    Mikrok.  d.  infectiosen  Osteomyelitis.     Deut.   med.  Wocli.,  1S83. 
Ullmann:   Fundorte  d.  Staphylokokken.     Zeitschr.  f.  Hyg.,  iv.,  1888. 
Wyssokowitsch  u.  Orth:   Beitr.  z.  I.ehre  v.  d.  Endocarditis.  Virch.  Arch.,  103  Bd., 
ISSG. 

§  155.  The  iVlicrococcus  Gonorrhoeas  or  Qonococcus  (Fig.  447)  is  a 
coccus  first  described  by  Xeisser  in  the  year  1879,  It  is  constantly  pres- 
ent in  the  discharges  oi"  the  purulent  catarrh,  know^n  as  gonorrhoea,  of 
the  male  and  female  urethra,  and  female  genital  caual  (especially  of  the 
cervix),  as  well  as  in  the  secretions  of 
gonorrhoeal  ophthalmia.  It  is  regarded 
as  the  cause  of  gonorrhoea  as  well  as  of 
the  blennorrhcea  of  the  eye.  Besides  the 
specific  cocci,  other  cocci  may  also  be 
present  in  the  gonorrhoeal  secretions,  some 
of  them  closely  resembling  the  gonococcus ; 
the  pus-cocci  may  also  be  present. 

The  gonococcus  may  be  cultivated 
njton  coagulated  human  blood -serum, 
blood -serum  gelatin,  on  human  blood-ser- 
uin-agar,  on  urine-agar ;  and  forms  on  the 
surface  of  the  nutrient  medium  a  thin 
grayish-yellow  layer  having  a  smooth  sur- 
face. It  dies  out  easily,  and  grows  only 
at   highei-  temperatures.     Wassermann  iccommeiKl 


FIG.  447. 
c.retifin  fi( 
(metliylcii 
single  t("i 
with,  c,  pi 
700. 


the  iiietbral  se- 
uf  ironorrhuM 
((,   Mucus  witl, 


iltnie-medium 


Fig.  m-Urethntis  frononlK.i.-a.  Cross-section  tliroiisrli  the  iniicous  membrane  whicli  had  beei 
thrown  into  folds  (Mullers  lluid,  lueiuiUo.xylin.  eosin).  o,  Noruial  connective  tissue;  h,  c,  intiammatory 
inflltrated,  proliferatiiif.^  connective  tissue  of  the  mucosa;  (/,  inlUtrated  and  desquamating  epithelium ;  e 
desquamated  epithelial  cells  and  pus-corpuscles.     X  KKI. 


c()\(K"()ccT's.  5.sr5 

s\viiics'-soruiuiintroso-a.uar;    M'citlicim.  i'  (..  ;>  ]):iits  of  :i  meat  boiiilloti 
]»optoiie-aiiai-  with  1  ])ail  of  st'iiini. 

TIic  ('(41  of  the  jioiiococcus  coiitMins  a  puisoii  (  Wasscnnaiiii  i  wliicli. 
when  injected  into  the  tissues,  excites  intlamniat  ion. 

Animals  are  ininuine  :iiiainst  inoculations  willi  tlie-unocuceus.  lOlfmis 
inadt^to  inoculate  lunuan  hein.us  with  aitilicially  culti\ale(l  <i()n<>c(icci  liave 
I  »eeu  successful  in  lu'oducin.ua  ])urulent  catanhof  the  inoenlaled  mucous 
membraue. 

lu  the  purulent  secretion  of  tiie  nincdns  niemiirane  infected  .\  :i  li  m.,,,. 
orrhcea  the  coccus  usually  forms  clumps,  and  for  the  i^reater  part  appears 
in  the  form  of  diplococci,  the  op{)()sinj;-  sr.rfaces  of  which  ai'e  llalteued 
(Fig.  447);  but  occurs  also  in  i)ait  free  (r/),  and  in  part  inclosed  within 
cells  (b).  It  stains  easily  with  aniline  d_\cs,  but  is  decolori/rd  1>\  (irain'> 
jnethod. 

The  gouococcus  penetrates  into  the  epithelial  layer  dl  the  alVecled 
liuieous  membraue,  aud  lies  partly  between  aud  i)artly  in  the  epithelial 
cells,  aud  iu  leucocytes.  Only  the  uppermost  layeis  of  the  connect i\«' 
tissue  are  infiltrated.  The  infiltration  is  most  marked  iu  the  case  of 
cylindrical  epithelium,  Avhile  iu  the  regions  covered  by  S(pianu)us  e])ithe- 
lium  (fossa  navicularis,  \agina)  the  cocci  lie  moie  sniierlicially.  'I'he\ 
cause  infiammatious  which  bear  the  character  of  jmndnif  <-(il<irrlis,  and 
are  associated  Avitli  a  cellular  iidiltration  of  the  tissue  of  tlie  mucosa 
(Fig.  448,  h,  c,  d)  and  with  epithelial  des(piamati()n.  'I'he  jnale  and 
female  urethra  aud  the  adjoining  parts  of  the  genital  glands  and  ducts, 
and  the  urinary  passages  form  the  chief  seats  of  locali/.at  ion.  Accoi-ding 
to  Scholz  there  occurs,  after  a  three-weeks'  duration  of  the  disease  in 
the  male  urethra,  a  metaplasia  of  cylindrical  cells  into  slratifu'd  s(|uam- 
ous  cells,  and  the  secretion  decreases  after  this  time.  To  what  extent 
the  deeper  inflammations  sofrecpiently  acc()mi»anyingor  following  gonor- 
rhcea  (peri-urethral  abscesses,  i)rostatitis,  e]ti(lid\  niitis,  Ncsiculitis,  cysti- 
titis,  inflammation  of  the  ducts  of  liartholin's  glands,  salpingitis,  ovai- 
itis,  pelvic  peritonitis,  arthritis,  etc.)  are  to  be  referred  to  the  spread  of 
the  gouococcus  or  to  what  extent  to  secondary  infections  by  the  pus-cocci 
is  yet  a  disputed  question.  According  to  the  investigations  made  u]>  to 
the  i)resent  time  there  can  be  no  doubt  that  the  gouococcus  may  become 
widely  si)read  over  the  surface  of  the  muc(uis  membiaues.  It  has  l)een 
many  times  demonstrated  in  the  blood  (Krause),  iu  the  inllamed  epididy- 
mis, tubes,  ovari(^s,  joints,  cardiac  vahcs,  tendon-sheaths,  Itnrsa-.  in  ])eri 
and  parametritic  foci  of  iidlammation,  and  in  ])eri-uret  liial  aliscesses. 
In  these  cases  it  has  been  regarded  as  the  cause  of  the  inllammation,  yet 
tin;  processes  which  lead  to  supj)Ui'ation,  and  even  the  metastases  in  dis 
taut  organs,  ap]>ear  to  l)emore  fieiiuently  dependent  upon  the  presence  of 
l>us-cocci. 

(ion(n-rhceal  infection  is  at  the  l)egiiniing  an  acute  process,  but  ma\ 
become  chroinc,  and  is  cured  only  Avith  great  dillicnlty;  since  the  gon«. 
cocci  can  maintain  themselves  here  and  thoc  in  the  nrethra.  tid»es.  etc.. 
for  yeai-s,  and  cnntiniH'  to  canse  inllai alimi. 

The  ironococcus  produces  u  ijoi.scjii  wliicli  rciiiaiiis  csseiitiiiliy  liniii.tl  ti>  tlic  cell 
and  only  slightly  passes  over  into  the  culture  tluid.  Tlie  existence  of  i\  poison  produc- 
ing an  antitoxin  has  not  yet  l)een  (lenionstrateil.  The  ix'st  of  tlie  fluid  cnltnre  inodiii 
is  the  one  advised  by  Wertheini,  consistin>r  of  2  to  :^  parts  meat  bouillon  with  one  part  ot 
blood  ssrum  (ascitic  or  pleuritic  fluid,  etc.). 

Cole  and  Meakins  (,/.  //.  //os/^  Bidl.,  11(07;  obtained  proniisiiiR  results  in  the 
treatment  of  gonorrhceal  arthritis  by  bacterial  inoculation.  Irmx  <.h»ir.  Infcrt.  Jh's^ 
1908)  also  obtained  favorable  results  in  the  similar  treatment  of  ponococcus  arthritic. 


584  THE    PATHOGENIC    FISSION-FUNGI. 

He  also  found  that  the  injection  of  dead  gonococci  into  individuals  suffering  from 
chronic  gonococcus  infections  gave  a  "  gonococcus-reaction  "  which  may  be  of  assist- 
ance in  diagnosis. 

Literature. 

(Gonococcus.) 

Bockhart:  Aetlologie    u.    Pathologie    d.     Harnrohrentrippers.     Vierteljahrsschr.     f. 

Derm.,  1883;  Secundiire  Infection  (Mischiufection)   b.    Tripper.     Monatsschr.    f. 

prakt.  Derm.,  1887. 
Brose:  Diffuse  Gonorrhoeal  Peritonitis.     Berl.  klin.  Woch.,  1896. 

Bumm:  Dor  Mikroorganismus  d.  gonorrhoischen  Schleimhauterkrankungen,  Wiesbad- 
en, 1886. 
de  Christmas  :  Le  gonocoque  et  sa  toxine.     Ann.  de  I'lnst.  Past.,  1897,  1900. 
Gushing.  Gonococcus  peritonitis.     Bull,  of  the  J.  Hopkins  Hosp.,  1899. 
Finger:  Die  Blennorrhoe  d.  Sexualorgane  u.  ihre  Complicationen,  Leipzig,  1896;  Die 

Syphilis  und  die  venerischen  Krankheiten,  Wien,  1901. 
Fritsch:  Die  gonorrhoischen  Krkrankungen  d.  weibl.  Sexualorgane,  Berlin,  1892. 
Ghon  u    Schlagenhaufer:  Zur  Biol.  d.  Gonococcus.     Wien.  klin.  Woch.,  1898. 
Haab,  0.:  Der  Micrococcus  der  Blennorrh.  ueonat.     Horuer'sche  Festschr.,  1881. 
Hartdegen:  Der  Gonococcus  Neisser  u.  s.  Bez,  zur  Gonorrhoe.     Cbl.  f.  Bakt.,  i.,  1SS7 

(Lit.). 
Heiman:   Studies  on  the  Gonococcus,  i.,  ii.,  iii.,  series.     Studies  from  Dept.  of  Path,  of 

Columbia  University. 
Jadassohn:   Path.  Anat.  d.  gonorrh.  Processes.     Verb.  d.  derm.  Congr.,  1894. 
Krause:    Die  Mikrokokken  der  Blennorhoea  neonatorum.     Cbl.  f.  Augenheilk.,  1882; 

Gonokokken.sepsis  u.  Nachweis  d.  Kokken  im  Blute.     Berl.  klin.  Woch.,  1904. 
Lang:   Der  venerische  Katarrh,  Wiesbaden,  1893. 

Lartigau:   Gonorrhoeal  Ulcerative  Endocarditis.     Amer.  Jour,  of  Med.  Sc,  1901. 
Martin:  Rech.  s.  I'inflamm.  metastat.  suppur.  a  la  suite  de  lagonorrhee,  Geneve,  1882. 
Neisser:  Cbl.  f.  d.  med.  Wiss.,  1879;   Deut.  med.  Woch.,  1882;  Bresl.  arztl.  Zeitschr. 

1886;  Bedeut.  d.  Gonokokken  f.  d.  Diagnose.     Arch.  f.  Derm.,  xxi.  Bd.,  Ergan- 

zungsh.,  1889.., 
Neisser  u.  Scholtz:  Gonorrhoe.     Handb.  d.  path.  Mikroorg.,  iii.,  Jena,  1903. 
Nobl:   Pathol,  d.  blennor.  u.  vener.  Lymphgefasserkrankungen,  Wien,  1901. 
Oppenheimer :    (Gonokokkengift)  Toxine  u.  Antitoxine,  Jena,  1904. 
Pelizari:   Gonokokken  in  periurethralen  Ab.scessen.     Cbl.  f.  allg.  Path.,  i.,  1890. 
Proschaska:  Die  gonorrhoische  Allgemeininfektion.     Virch.  Arch.,  164  Bd.,  1901. 
Schaffer:  (Jonokokken.     Ergebn.  d.  allg.  Path.,  iii.,  1897  (Lit.),  u.  vii.,  1902  (Lit.). 
Scholz:   Zur  Biologic  d.  Gonococcus.     Arch.  f.  Derm.,  49  Bd.,  1899. 
See:    Le  gonococpie,  Paris,  1897. 

Steinschneider:    Kultur  der  Gonokokken.     Berl.  klin.  Woch.,  1893. 
Thayer  u.  Blumer:    Endocardile  blennorhagique.     Arch,  de  med.  exp..  1895. 
Thayer  and  Lazear:    Gonorrhoeal   Septicaemia  and  L^lcerative  Endocarditis,  with  Ob- 
enervations  upon  the  Cardiac  Complications  of  Gonorrhoea.     Jour,  of  Exp.  Med., 

1899  (Lit.). 
Touton:   Ueber  Folliculitis  praeputialis  et  paraurethralis  gonorrhoicn.     Vierteljschr.  f. 

Derm.,  xxv.,  1889;   Der  Gonococcus  u.  s.  Bez.  z.  Blennorrhoe.     Berl.  klin.  Woch., 

1894. 
Wassermann:    Gonokokkenkultur  u.  Gonokokkengift.     Berl.  klin.  Wocli..  1S97. 
Wertheim:    Die  ascendirende  Gonorrhoe  beim  Weibe.     Arch.  f.   (Ivti.,   42  Bd.,   1892. 
V.  Zeissl:   Lehrb.  d.  veneri.schen  Krankheiten,  Stuttgart,  1902. 

i^  !.")(;.  Cocci  liave  been  demonstrated  with  certainty  as  the  cause  of 
disease  in  animals  in  tlie  case  of  a  Lirge  nnmber  of  infections  diseases, 
and  ai-e  regarded  with  probabilil y  :is  the  canse  in  tlie  case  of  others.  As 
has  already  been  stated,  the  Streptococcus  pyogenes,  the  Diplococcus 
pneumoniae,  and  the  Hicrococcus  pyogenes  aureus,  citreus,  and  albus 
are  also  ])athogenic  foi-  different  animals,  and  the  la.st-named  in  particn- 
lar  often  canse  spontaneons — not  cansed  by  inocnlation — snpi)nrative 
inflammations  in  animals.  The  disease  occnrring-  in  colts  and  calves 
known  as  staggers,  characterized  by  inflammations  of  the  joints,  is  a 
staphyloeoccns  and  streptococcus  infection  occnrring  through  the  navel, 


PATIKHIKXrC    COCCT.  535 

niul  belongs  to  tlio  group  of  soptieopvivmic  processes.  ^Nforcover,  disenscs 
luive  also  been  i>roduee(l  experimentally  in  animals  by  dilTcrent  cocci 
which  were  not  pathogenic  for  man.  Furtlier,  in  nnmy  sjionlancons  dis- 
eases of  animals  cocci,  that  are  j^robably  to  be  regarded  as  the  cause, 
Inive  been  demonstrated. 

(1)  According  to  .S-A///r("  Dcr  Sticiitococcusdcr  Druse  dcr  Pfcnlc,"  ,l;r//.  f.  ?r/.v.v.  ir, 
prakt.  TInerluilk.,  xiv.,  ISSS;  Zat.f.  Umiuni.  iii.),  .S^//^/iiiid,/(7/.v('//  ("  Die  Actioloi,Mcd<T 
DrvLse,''  DfHd^rh.  '/aH.J'.  Thirmud.,  xiii.).  and  /'w/'n  ("  Die  .Mikrokokkcn  dcr  Dnisc  dcr 
Pferde,"  Fortschr.  a.  Med.,  vi.)  the  strangles  of  horses  is  au  infectious  disease,  in  wiiicii 
the  mucous  membrane  of  the  upper  respiratory  tract  is  the  seat  of  a  nuicopuruieni 
iuflammation,  iu  Avhich,  moreover,  the  lympli-giands  pertaining  to  the  region  become 
swollen  and  iu  part  suppurate;  and  is  caused  "by  a  r/«;///-/o;'////w/7  twr//«,  which  can  l)e 
cultivated,  and,  when  inoculated  into  horses  {Sc/iiitz)  again  produces  the  disease. 

(3)  According  to  Schiltz  ("'Die  Ursachen  der  Brustseuche  des  Pferdes,"  .1/r//./.  vr/x- 
sensch.  u.  prakt.  Thierheilk.,  1887;  Virch.  Arch.,  107  Bd.,  1887)  the  epidemic  liii,f/-di.'<- 
ease  of  horses  (infectious  pneumonia)  is  caused  by  au  oval  coccti.<i,  which  forms  pairs  and 
chains,  and  is  not  ideutical  with  the  Diplococcus  pneumoniie  (Friinkel)  or  the  Bacillus 
pneumonia'  (Friedliinder),  and  therefore  not  identical  with  the  bacterium  described  l>y 
Perroncito  {Arch.  ital.  cle  biol.,  vii.,  1886)  as  occurring  in  the  pneumonia  of  horses,  anil 
held  by  him  to  be  identical  with  the  Diiiiococeus  imeumonite. 

(3)  According  to  Poels  and  Nolcn  ( Fort.'ich.dcr  }[pd.,iy.,  1886),  monococci  and  diplo- 
cocci,  which  in  part  possess  a  gelatinous  caitsule,  are  found  constantly  in  the  lungs  and 
in  the  pleural  exudate  in  the  contagious  pleuroiinciimonia  of  cattle.  On  gelatin  and  agar- 
agar  they  form  chiefly  white  colonies  which  later  become  cream-oolored.  Pvn-e  cultures 
injected  into  the  lungs  of  rabbits,  guinea-pigs,  dogs,  and  cattle  give  rise  to  pneumonic 
changes.  According  to  F/'(>(/6e;'^(r  and  /'>o/mer("Spe/..  Patliologie."  Stuttgart,  1896), 
the  infective  material  is  not  knowii  with  certainty. 

(4)  In  the  vdder-iyiflammations  of  the  domestic  animals,  which  occur  sometimes 
sporadically,  sometimes  epidemically,  different  micrococci  and  streptococci  have  been  de- 
scribed, and  designated  by  various  names  (Hcsa  and  Bergeand,  "Contag.  Euterentziin- 
dung.  gelber  Gait  genannt."  Schweiz.  Arch./.  Thierheilk.,  30  Bd.,  1888;  Frank,  "Euter- 
entziindungen,"  Dtsch.  Zeil.  f.  Thiermed.,  ii.,  1876;  Kitt,  "Euterentziuulung,"  "Lehrl). 
d.  path.  anat.  Diagnostik,"  Stuttgart,  1894;  Jensen,  "Mastitis,"  Ergebn.  d.  allg.  Pallt., 
iv.,  1899). 

(5)  According  to  Johns  ("Seuchenart.  Cerebrospinahucningitis  d.  Pferde,"  Dlsch. 
Zeitschr.  f.  Thiermed.,  xxii.,  1887),  the  cerebrospinal  meningitis,  which  occurs  epidemi- 
cally in  horses  is  caused  by  the  Diplococcus  intracellularis  meningitidis  {Weichselbaum, 
§    153). 

(6)  Babes  found  in  the  hsemoglobinuria  of  cattle,  which  occurs  as  an  epidemic 
disease  in  Roumania,  a  coccus  similar  to  the  gonococcus,  which  he  regards  as  the  cause 
of  the  disease  ("Sur  I'hemoglobinurie  bacterienne  du  boeuf,"  Comjit.  rend,  de  I'Acail.  dcs 
Sciences  de  Paris,  cvii.,  1888;  Virch.  Arch.,  115  Bd.,  Annal.  de  riustitut  de  palhol.  <i 
Bucarest,  1890). 

(7)  .\ccording  to  Rivolta  and  Johne  (Dlsch.  Zeitschr./.  Thiermed..  xii.;  "Hericht 
ijber  das  Veterinarwesen  im  Konigr.  Sachsen  f.  d.  J.  1885")  and  Pabe  (Dtsch.  Zeitschr. 
f.  Thiermed.,  xii.),  there  occurs  in  horses  a  peculiar  tumor-like  growtli  of  coimective  tis- 
sue, designatetl  by  Johne  as  mycofibroma  or  mycodesmoid,  which  is  caused  l)y  a  micrococ- 
cus that  grows  in  animal  tissues' in  round  or  grape-like  colonies  wiiich  (piickly  become 
surrounded  by  a  hyaline  capsule,  and  are  therefore  to  be  reckoned  as  a.sYv>rorr('  (M icro- 
rorcus  ascoformans).     Bollinger  and  Glage  designate  the  Cf)ccus    as  Bolrifomi/ccs.  Bahe. 

|^  .M icrococcn^'i  botrj/ogene.^.  Kitt  as  Botryococcus  ascojonnons.  The  growths  consist  (tf 
loimective  tissue,  reseml)ling  those  of  actinomycosis,  and  enck)se  small  suppurating 
I'lci  of  granulation  tissue  wliieh  contain  the  fungi.  'I'hej'  appear  to  devi'lop  most 
trequently  in  the  spermatic  cord  after  castration,  l)Ut  (.ccur  also  on  other  parts  of  the 
l>o(iy,  particularly  in  the  skin  (Kilt,  "Der  .Mi(ioid(<iH  ;i>coformans  uud  das  MycoH- 
l)rom  des  Pferdes,"  CM.  /.  Bakt.,  iii.,  ISSS;  Srhn,;,l<,nuhl.  '•  Botryomyeosis,"  Chi.  /. 
Bakt.,\xW.,  1898  [Lit.];  dlagc:  "  Botrvomvkos.-."  "  liaiHll..  .1.  palliog.  Mikroorg.,"  iii., 
Jena,  1003). 

(8)  According  to  r::berth  (Virch.  Arch.,  80  B.l.i  and  .U.  Wolff  (Virch.  Arch.,  92 
Bd.),many  of  the  gray  parrots  brought  to  K)iroi)e  (P.-iltonis  erithacits)d\v  of  a  .strei)to- 
coccus  myco.sis.  The  micrococci  are  found  in  almost  all  the  organs.  l)Ut  especially  in 
the  capillaries  of  the  liver  and  their  neighborhood,  where  they  cause  necrosis  of  the 
liver-cells,  but  no  suppuration. 

(9)  According  to  0.s;ertoi7('-Handb.d.pathog.Mikroorg.,'  u.),  the  infective  vaginal 
catarrh  of  cattle  is  caused  by  a  streptococcus. 


586  THE    PATH(3GENIC    FiSSIOX-Fl  XGI. 

2.    The  Bacilli    and    the    Poltmoephof.s    Bacteria,    axd    the 
Pathological  Processes  Produced  by  The:\[. 

(«)  General  Considerations  Regarding  BaeiJIi  and  the  Polipnorphons  Bacteria,.. 

§  157.  Under  the  desiguatiou  bacilli  or  bacillaceae  (A.  Fischer)  or  i 
Bacteriacew  (Zopf)  may  be  classed  all  those  Ijucteria  Avhich  occur  iu  the  | 
form  of  strai.uht  rods  or  rods  which  are  slightly  bent  in  one  plane.  By 
inauy  authors  (Colin,  Hiippe,  Lehmanii)  the  bacillacese  are  divided  into 
two  groups:  bacterium  and  bacillus,  the  latter  being  characterized  by 
the  production  of  endogenous  spores,  while  spore-formatiou  is  lacking 
iu  the  former. 

The  bacilli  multii)ly  by  division.  The  rods  grow  in  length,  and  di- 
vide into  ai)proximately  equal  parts  through  the  formation  of  a  trans- 
verse partition-wall.  If  the  division  of  one  of  the  elongating  bacilli  is 
delayed,  or  if  the  separation  of  the  indi^  idual  rods  from  one  another 
is  not  distinctly  recognizable,  there  arise  long,  unbranched  rods  or  threads 
(Fig.  450,  h).  If  the  divided  rods  remain  attached  to  each  other,  there 
are  formed  chains  of  rods  (Figs.  449,  e:  450,   <■).      In   many  forms  of 


1' IG.  449.  FIG.  ir,0. 

Fig.  449.— Bacillus  subtilis  in  various  stages  of  development  (Prazmowski).  a.  Single  rods;  h,  rods 
with  flagella ;  c,  chain  of  rods ;  t?,  single  cells  with  spores ;  e,  chain  of  rods  with  spores ;  f  '  — ^,  germination 
of  a  spoi-e.    X  mi 

Fig.  4r)n.— Clostridium  butyricum  (Prazmowskii.  a.  Short  mils :  ?>,  Idiig  rmls  :  c,  chain  of  rods  ;  d,  cells 
with  spores  ;  c  '— ",  germination  of  a  spore.    X  8(KJ. 

l>acilli  llicciids  of  the  individual  rods  are  liliinl,  in  others  rounded  or 
]M. luted. 

In  many  bacilli,  resting  as  well  as  swarming  stages  are  observed. 
I'lagella  serve  as  the  organs  of  motion  (Fig.  449,  h);  they  are  situated 
sometimes  at  the  ends,  sometimes  on  the  sides,  of  the  rods,  and  ma>  occur 
in  large  numbers.  In  many  bacilli  an  endogenous  spore=formation  is 
observed  (Figs.  449,  d,  e ;  450,  d),  the  spores  lying  sometimes  in  the 
middle,  sometimes  at  one  end,  of  the  cell.  Not  infrequently  the  spores 
ap|)car  within  jointed  threads.  The  germination  of  spores  results  iu  the 
loiiiialion  of  new  rods  (Figs.  449,  /'',  450  e'''). 

Duiing  s[)ore-formation  the  rods  usually  do  not  change  their  shape: 
1o  any  marked  extent.  In  other  cases  they  as.sume  a  spindle-,  club-,  or 
l»eai'-shape  (Fig.  450,  d),  and  these  changes  have  been  taken  as  the  basis 
loi- the  establishment  of  an  especial  group,  etostridiunt.  On  the  other 
hand,  nunu'rous  authors  class  these  forms  with  the  bacilli. 

Tlie  polymorphous  bacteria  are  distinguished  from  the  bacilli  by  the 
fact  that  tliey  foi  in,  besides  rods,  also  long  threads,  in  part  with  false  or 


SAPHOlMlVriC    HACII.LI.  587 

truebraiu'liiiij;-;  and  in  individual  cases  a  basal  non-prolift'ralinfi:<'nd  and 
an  apical  piolifcratin^ii-  end  may  be  distin.unislic<l.  In  liiis  cafc<;orv 
may  be  ])laced  tlie  fnnjii  desiiiuated  Slnjitollnix,  Chulotlnix,  Ii/(/f/iat<K(, 
and  Crniot/n-i.v.  Tliey  are  liere  i)laced  with  the  bacilli,  becmist',  on  tin- 
one  hand,  their  botanical  jxtsition  is  not  (lelini1«-ly  determined,  while,  on 
tli<'  other,  in  so  far  as  they  are  ])atli(»,ii('iiic.  they  confoiin  most  closely  to 
the  bacilli  in  their  biolo^ie:ll  inopert ies  (r/".  dipht heiia-bacilli,  tiibeiVh'- 
bacilli,  and  actinomyces). 

Tlie  saprophytic  bacilli  i»rodnce  many  forms  ol' fmnnihilion  by  their 
growth  ill  initiient  fluids;  many  also  f(»rm  7>//////r/*^s.  .\.  sharp  line  can- 
not be  draMu  between  the  saprophytic  bacilli  and  the  pathoj-enic  forms, 
since  some  saphropliytes  (I'rotrit.s  viilgcnis,  Barifhis  ]>i/()(-i/<nirii.s,  J>.  trtani, 
B.  mlrmafis  i/(r<////;//)  occasionally  develoj)  also  in  theliuman  oi'jianism. 
Some  also  form /o.r///.s  (/>.  hi>iiilhiuH,B. pyociidjinis)  Mhich  wlien  taken  into 
the  oriianisni  ])roduce  intoxication. 

Bacillus  botulinus  (Van  Ermengem)  is  an  obligate  anai-robic  bacillus 
which  develoiJS  occasionally  in  sausage,  particularly  in.  lilood  and  liver 
sausages,  also  in  smoked  meat,  canned  meats,  game  pies,  salted  fish,  and 
also  in  preserved  fruits  and  vegetables.  The  liacillus  is  (Van  Ermen- 
gem) 4-6  //.  long,  0.9-1.2  ,a  broad,  and  possesses  4-S  periplu'rally  arranged 
Hagella.  It  stains  according  to  Gram.  In  the  ordinary  nutritive  media 
it  grows  best  nnder  anaerobic  conditions  at  a  temju'ratnie  of  1S°-L'.">°  ('., 
and  forms  endogenous  spores.     Acids  easily  inhibit  its  growth. 

When  growing  in  the  foods  mentioned  abo\e,  it  produces  a  true  toxin 
which  is  very  jioisonous  for  experimental  animals,  and  causes  the  forma- 
tion of  an  antitoxin.  The  poison  is  rendered  inactive  by  heating  to  80° 
V:,  but  is  not  changed  by  the  digestive  juices.  The  consumption  of  foo<l 
in  which  the  bacillus  has  already  formed  its  toxins  lea<ls,  therefore,  t(> 
intoxication.  On  the  other  hand,  the  bacillus  does  not  develop  in  the 
luiman  organism,  its  growth  being  hindered  by  the  high  body  t«Mni>era- 
ture.     The  bacillus  should  be  classed  then  as  a  ioxicojicnic  ,s(i/)roj)/ii/lr. 

The  disease  known  asbotulismus  or  allantiasis  or  ichthyoismus  comes 
on  about  twenty-four  to  thirty-six  hours  after  the  taking  of  the  food, 
and  is  characterized  essentially  by  nerxous  dist  urbances  of  cential  origin, 
secretory  disturbances,  motor  paralysis  (i)aralysis  of  accommodation, 
mydriasis,  i)tosis,  and  donble  vision),  dryness  and  redness  of  the  mucous 
membiane  of  mouth  and  pharynx,  aphonia,  dyspliagia,  etc.  ronsti]>a- 
tion  and  retention  of  ni-ine  frecjuently  take  ])lace,  or  thei-e  may  ])e  diai- 
rhoea  and  vomiting.  Death  often  results  after  a  short  time  through 
bulbar  paralysis. 

.Vs  Proteus  vulgaris,  Hausei-  has  described  a  bacillus  {lUiclirimn  rul- 
f/are  of  Lehmann)  which  is  very  fre(jneiitly  ])resent  in  d«'conii)osi'ig  ani- 
mal substances  and  in  human  cadavers,  and  in  gangivnous  ulcers,  and 
causes  putrid  decomposition.  It  forms  rods  of  varying  length,  and  i>i'o 
duces  substances  i)oison()us  for  animals.  According  to  observations  b\ 
numerous  authors,  it  is'^not  infrequently  found  in  liuman  iissKts,  chirlly  in 
association  with  other  bacteria,  streptococci,  ])neuino<'ocei,  <li|»litlieria 
bacilli;  and  by  its  presence  aggravates  the  course;  of  the  infection  and 
causes  2>»//vV7  f^/VY'o>//y>o.s77/o// of  tlu;  ])us  and  the  necrotic;  tissue.  In  rare 
cases  it  may  oIoih;  without  the  association  of  other  bacteria,  aitisr  iiifhtni- 
mathns,  particularly  of  the  urinary  bladder  (ri/.sfiti.s).  Several  cases  of 
hcemon-}i((f/ir  ctitrriti.s  have  also  been  described,  in  which  a  form  of  ]>rolcus 
was  regarded  as  the  causal  agent.  Further,  prot<Mis  has  also  been  found 
in  iuHammations  of  the  female  genital  tract,  scrims  membraiu'S,  and  liver 


588  THE    PATHOGENIC    FISSION-FUNGI. 

(infections  ioterns),  and  has  been  considered  to  be  the  canse  of  the  given 
iuflamniation.  Proteus  mnst  therefore  be  chissed  with  the  panmtic  or 
ixithogemc  hactrria.  Its  i)athogenic  activity  rests  chiefly  npon  tlie  forma- 
tion of  poisonous  snbstances.     (Literatuie  given  by  Meyerhof,  1.  c). 

The  pathogenic  bacilli  and  polymorphous  bacteria  canse  partly 
acute  and  partly  chronic  affections,  the  former  terminating  either  in 
death  or  in  iienling  after  the  destruction  of  the  bacteria.  It  also  hap- 
pens iu  the  acute  diseases  that  the  bacteria  may  remain  in  the  body  for 
a  long  time.  The  chronic  affections  are  characterized  by  the  persistence 
and  multiplication  of  the  bacteria  within  the  body,  so  that  the  disease 
assumes  a  progressive  character,  and  sometimes  slowly,  sometimes  rapidly, 
new  regions  are  in  turn  Invaded  by  the  bacteria  and  suffer  pathological 
changes. 

Bacillus  subtilis  is  a  fission-fungus  whose  spores  are  widely  distributed  in  the 
ground,  hay  (hay-bacillus),  and  in  the  air.  When  cultivated  upon  potato  or  upon 
the  dung  of  herbivorous  animals,  it  forms  whitish-yellow  colonies;  upon  liquids  it 
forms  thin  and  thick  pellicles.     It  requires  oxygen  for  its  development. 

The  fully  developed  rods  (Fig.  449,  a)  are  6  /«  long.  The  snake-like  motions 
occurring  at  times  are  produced  by  means  of  numerous  lateral  and  terminal  flagella. 
Through  the  growth  of  the  rods  undivided  threads  are  formed  which  after  division 
form  chains  of  rods.  The  separate  cells  may  develop  in  their  interior  glistening, 
.sharply  contoured  spores  ((/,  e),  which  lie  either  in  the  middle  or  nearer  to  one  end  of 
the  cell.  Later  the  cells  in  which  the  spores  have  been  formed  die.  During  germina- 
tion the  spores  become  pale  (Fig.  449/,  '-=),  lose  their  glistening  appearance  and  their 
sharp  contour.  A  shadow  then  appears  at  each  pole,  while  the  spore  begins  a  tremu- 
lous motion.  After  a  time  the  contents  of  the  spore  project  from  the  membrane  of 
the  spore  in  the  form  of  a  germinal  utricle,  which  later  becomes  elongated,  divides, 
and  produces  swarming  rods. 

The  Bacillus  butyricus  (Bacillus  amylobader  of  Van  Tieghem,  Vlbrion  butyrique 
of  Pasteur,  Clostridium  butyricum  of  Prazmowski)  consists  of  rods  of  3  to  10 ,«  in 
length,  and  also  forms  threads  and  chains  of  rods.  During  spore-formation  the  cells 
become  spindle-,  club-,  or  tadpole-shaped  (Fig.  450,  d),  and  then  produce  one  to  two 
glistening  spores.  In  germination,  after  the  absorption  of  the  spore-membrane  a 
germinal  utricle  appears  at  one  of  the  two  poles  (Fig.  450,  e^-~);  this  becomes  elon- 
gated, and  produces  new  rods  by  segmentation. 

The  Bacillus  butyricus  does  not  need  oxygen  for  its  development;  it  produces 
butyric-acid  fermentation  with  evolution  of  carbonic  acid,  in  solutions  of  starch, 
dextrin,  sugar  or  glycerin.  In  media  containing  starch,  glycerin,  or  cellulose  the 
bacilli  are  colored  lilue  with  iodine. 

Bacillus  prodigiosus  grows  upon  potatoes  and  bread,  as  well  as  upon  agar- 
agar,  and  upon  nutrient  gelatin,  liquefying  the  latter.  It  forms  a  red  coloring  matter 
which  is  soluble  in  alcohol.  The  pigment  is  formed  only  in  the  presence  of  oxygen: 
in  the  growth  in  milk  the  coloring-matter  is  contained  in  the  fat-droplets.  The  bacilli 
themselves  are  always  coloi-less. 

Bacillus  fluoriescens  liquefaciens  forms  whitish  cultures  in  gelatin,  in  the 
neighborhood  of  which  the  gelatin  is  liquefied,  while  in  the  remote  surrounding 
portions  it  grathially  takes  on  a  greenish-yellow  fluorescence. 

Bacillus  cyaiiogenes  (Xeelsen,  Hucppe),  when  cultivated  in  steriUzed  milk, 
causes  a  slate-gray  color  that  changes  through  the  addition  of  acid  to  an  intense  blue. 
In  unsterilizecl  nulk,  in  which  lactic-acid  bacteria  develop  at  the  same  time,  a  blue 
color  appears  without  the  addition  of  acid.  On  potatoes  it  forms  yellowish,  slimy 
cultures,  in  the  neighborhood  of  which  the  substance  ot  the  potato  is  colored  grayish- 
blue  (FliKiqc). 

Bacillus  acidi  lactici  ferments  milk-sugar  into  lactic  acid  and  coagulates  casein. 
In  gelatin  it  produces  white  cultures. 

Bacillus  caucasicus  (Dispora  caucasica)  forms  one  of  the  constituents  of  the 
fungus-conglomerate  known  as  kephir-ferment,  which  is  used  by  the  inhabitants  of 
the  Caucasus  in  the  i)reparation,  from  cow's  milk,  of  the  alcoholic  drink  called  kephir. 
The  kephir-ferment  consists  of  small  granules  containing  yeast-cells  and  bacilli.  The 
latter  at  times  show  movements,  and  form  a  round  spore  at  the  end  of  each  rod.  As 
the  result  of  their  growth  in  milk  the  milk-sugar  is  probably  converted  into  glucosft. 
while  the  yeast-cells  produce  alcoholic  fermentation. 


ANTHRAX.  5.S9 

Bacillus  pyocyaneus  occurs  oconsionnlly  in  hamlnRcs  upon  sui>|)iimtiii,<i  wouikIs 
and  causes  a  iiirenisli-hlue  discoloration  of  tiic  same.  Tiic  coloriufi-iiiaf icr  called 
pijocyanin  is  soluble  in  chloroform  and  crysfalli/A's  from  tlie  solution  in  lonu'  l)lue 
needles.  In  addition  it  forms  also  a  colorinji  matter  solul)le  in  water  which  produces 
a  greenish  fluorescence  of  the  nutrient  gelatin.     (S^ee  §  lG;i.) 

Literature. 

{Saprophjitir   [jii    Pari    Pdl/iot/ciiic]    liadl/i.) 

Babes:  Rech.  sur  les  bacilles  du  i)us  vert.     Ann.  dc  I'lnst.  de  path,  dc  Boucarest    i 

1S90.  '    ■' 

Banti:    Sopra  quatri  nuove  specie  di  Protei  o  Bacilli  capsulati.  Firenzc,  1888. 
Bordoni-TJffreduzzi :    Proteus  hominis  capsulatus.     Zeitschr.  f.   Hyg..  iii.,  1888. 
Bunge:  ( ieisselfragende  Bakterien.     Fortschr.  d.  Med.,  .\ii.,    1894;"  t^ijorenbihiuiur 

lU.,  xiii.,  1S95. 
Carbone:   I'eber  die  von  Proteus  vulgaris  erzeugten  Gifte.     ("bl.  f.  Bakt.,  viii.,  1890. 
van  Ermengem:  Bacillus  botulinus.     Z.  f.  Hvg.,  26  Bd.,  189V,u.  Handb  d.   path 

Mikroorg..  ii..  Jena,  1903  (Lit.). 
Ernst:    Bacillus  des  blauen  Eiters.     Zeitschr.  f.  Hyg.,  ii..  1887. 
Foa  ft  Bonoine:  Maladies  causees  par  Proteus.     Arch.  ital.  de  Biol.,  vii.,  1887. 
Frankel:  Ueber  GaspUegmone,  Leipzig,  1893. 
Frick:   Griines  Sputum  u.  griinen  Farbstoff  produc.  Bacillen.     \'irch.  Arch.,  IKi  Bd.. 

1S89. 
Gessard:   Rech.  sur  le  microbe  pyocyanique.     Ann.  de  I'lnst.  Pasteur,  1890. 
Goebel:   Bacillus  d.  Schaumorgane.     Cbl.  f.  allg.  Path.,  vi.,  189o. 
Grethe:   Keimung  d.  Bakteriensporen.     Fortschr.  d.  Med.,  xv.,  1897. 
Hauser:    Feb.  Fiiulnissbakterien  u.  deren  Beziehung  z.  Septikiimie,  Leipzii;-,  188.").  . 
Helm:   Versuclie  liber  blaue  Milch.     Arb.  a.  d.  K.  desuiullieitsamte,  v.,  1890. 
Jaeger:   Die  Aetiologie  des  infectiosen  fieberhaften  Ikterus.     Zeitschr.  f.  ilvi:.,  xii., 

1892. 
Jakowsky:  Bakterien  des  blauen   Eiters   (B.  pvocyaneus).     Zeitsclu-.   f.  Ilvg.,  xv., 

1893. 
Krause:    Zur  Kenntn.  d.  Bac.  pyocyaneus.     Cbl.  f.  Bakt.,  xxvii.,  1900. 
Lartigau:   Bacillus  pyocyaneus  as  a  Pathological  Factor.     Piiil.  Med.  Jour.,  1898. 
Ledderhose:   Ueber  den  blauen  Eiter.     Deut.  Zeitschr.  f.  Chir.,  xxviii.,  1888. 
Levy;   Die  Aktinomycesgruppe.     Cbl.  f.  Bakt.,  xxvi.,  1899  (Lit."). 
Meyerhof:   Biologische  u.  thierpathogene  Eigenschaft  des  Bacillus  proteus  (Hauser), 

mit  einer  Zusammenfassung  d.  wichtigsten  Literatur  iiber  Proteus.     Cbl.  f.  Bakt.. 

xxiv.,  1898. 
Prazmowski:   Unters.  iiber  d.  Entwickelungsgeschichte  einigei    Bakteiien,    Leipzii;. 

1 880. 
Perkins:   Report  of  Nine  Cases  of  Infection  with  P.acillns  I^■(l(■v;ln(■M^.   .loui-.  of   Alcd. 

Research.  1901. 
Schimmelbuscli:    Griiner  Eiter  u.  d.  Bac.  iiyocyaneus.     S.iiinnl.  Idiii.  N'orl  r.,  Xo.  (■)2, 

is'j:!. 

•■*  (/>)   T/ic  Pafhoffenic  Bacilli  <iii<J  PDhiiDotjihons  lUtrtn-iit. 

S  158.  The  Bacillus  anthracis  (Jjortrridir  <li(  r/i((ihoii)  is  tlic  rmisc  of 
anthrax,  a  disease  oeeuiiinj;  ehietly  in  cattle  and  slieep,  and  occasionally 
transmitted  to  man.  It  is  a  lission-funjius  which,  ^vllen  inoculated  into 
a  sn.sce])til)le  animal,  may  increase  witliin  the  ti.ssues  as  well  as  in  tlie 
blood. 

The  anthrax=bacilli  (Fi<;-.  l.-)!)  are  8  to  10  //  lonj;  and  1  t..  !.".//. 
hroad.  In  tlie  blood  of  animals  affected  with  anthi-a.x  they  occur  eiliier 
singly  or  in  thread-likejointed  bands  of  two  to  ten  lods,  who.se  ends  ar«' lor 
the  greater  part  sliarply  cut  across  (Fig.s.  4.")1,  4.")2)  more  iar<']y  slightly 
concave  or  even  slightly  convex  (.Tohne).  Ac<'ording  to  Piane.se.  Seia 
tini,  Giinther,  and  Johne  they  possess  a  gelatinous  capsule  wliich  is  Im'sI 
brought  out  by  the  staining  of  dried  jui-paral ions  with  metliylene  l)]ne. 
They  can  be   cultivated   upon    blood-serum-gelatin,    in    Ixmillnn,    njxin 


590 


thp:  pathogenic  Fissiox-rrNGi. 


Fig.  451.— Section  from  a  liver  whose  capillaries 
contain  numerous  anthrax-bacilli  and  scattered 
leucocytes  (alcohol,  gentian-violet,  vesuvin).  X 
300. 


slices  of  potiitoes  and  turnips,  in  infusions  of  peas  and  mashed  grain  of 
various  liinds,  etc.,  in  the  presence  of  oxygen  (according  to  Klett  also 
in  an  atmosphere  of  nitrogen)  ;  and  grow  most  rapidly  at  a  temperature 
of  from  30°  to  40"  C.  At  temperatures  below  15°  and  above  48°  C. 
development  is  imijossible. 

Under  suitable  conditions  of  growth  the  rods  increase  in  length,  and 
may  within  a  few  hours  form  non-encapsulated  threads  of  considerable 

length.  These  consist  of  sliort  seg- 
ments whose  outlines  may  be  made 
visible  by  treatment  with  iodine  or 
by  stains  (Fig.  452).  -Ten  hours 
later  the  clear  contents  of  the 
threads  become  granular,  and  at 
regular  intervals  there  become  ap- 
parent dull-shining  bodies,  which 
after  a  few  hours  enlarge  into 
strongly  refractive  spores  (Fig. 
452).  Later  llio  threads  disinte- 
grate and  the  spores  become  free. 
If  the  bacilli  or  the  spores  gain 
entrance  into  the  blood,  they  in- 
crease and  form  rods  as  described 
above,  which  stain  with  different 
aniline  dyes,  and  also  by  Gram's 
method.  Sections  of  hardened 
tissue  sliow  that  they  are  present 
in  large  numbers  in  the  capillaries  (Fig.  451),  ijarticularly  in  the  spleen, 
liver,  lungs,  and  kidneys.  The  neighboring  parenchyma  for  the 
greater  part  appears  unchanged ;  still  the  local  proliferation  of  the  ba- 
cilli can  also  cause  tissue-degeneration,  necrosis,  and  haemoi-i'hagic  in- 
flammation. If  an  infection  of  the  blood  takes  place  during  i^reg- 
nancy  the  infection  may  pass  over  to  the  foetus. 
Anthrax-bacilli  or  their  spores  may  gain 
entrance  into  the  skin  of  man  thi-ongh  small 
wounds,  an  event  which  is  particularly  likely  to 
happen  in  the  case  of  individuals  who  butcher, 
or  shear,  or  prepare  the  skins  of  animals  affected 
with  anthrax;  or  occasionally  the  infection  may 
be  transmitted  by  means  of  tJie  sting  of  a  fly 
which  has  taken  up  blood  from  an  animal  in- 
fected with  anthrax.  There  develops  at  the 
place  of  infection  a  somewhat  elevated  pustule 
(Fig.  453)  from  G  mm.  to  several  centimeti'es  in 
diameter,  having  an  arched  or  flattened  surface, 
and  of  a  red  or  at  times  a  more  yellowish  color. 
This  is  often  after  a  time  covered  with  vesicles, 
or  after  the    loss  of  the  epithelium    becomes 

moist,  so  that  through  the  drying  of  the  oozing,  often  bloody  exudate, 
a  scab  is  formed  (Fig.  453,  g'). 

The  centre  may  become  depressed  through  the  formation  of  a  central 
scab,  so  that  the  edges  form  a  wall  about  the  latter.  The  neighborhood 
of  the  pustule  is  sometimes  but  slightly  changed,  at  other  times  reddened 
and  swoll(;n,  and  may  be  set  with  small  yellow  or  bluish-red  vesick-s. 
If  the  process  remains  local,  the  gangrenous  pustule  may  be  thrown  off. 
Infection  of  the  blood  is  fatal.     In  rare  cases  the  infection  from  the 


Fig.  452.  —Spore  -  containing 
anthrax-bacilli  and  free  spores, 
rover-glass  preparation  from  a 
culture  of  the  bacilli  crown  in 
the  incubator  upon  pota,to,  and 
stained  with  fuchsin  and  nieth- 
ylene-blue.    X  800. 


AXTHHAX. 


591 


j      beginnino:  may  show  itself  as  an  exlensivo,  iiilcnsc,  (odoinatous  swclliiiu 
of  the  tissue  Avithoiit  tlie  fonnation  of  a  circumsciil)o(l  elevaliou. 

In  the  region  of  a  fully  th'veloped  anthra\-i)ustuU>  (Fig.   -ioli),  ilie 
wrinm  (d,  d,)  and  tlie  pai)illary  body  (r)  are  iulill rated  with  a  sei-oci'llnlar 

e 


.rfjS^ 


J^l 


Fig.  453.— Section  from  an  antbrax-puslule  ten  days  old,  taken  from  the  arm  of  a  man  falcohol. 
Gram's  method,  vesuvin).  a,  Epidermis ;  b,  eorium  ;  c,  papillary  body  oedematously  swollen  and  intlltrated 
with  exudate  and  bacilli:  d,  outer  layer  of  eorium,  intlltrated"  with  cells;  d,,  the  same,  ((intaininir  alsfj 
bacilU;  e,  deep  layers  of  the  eorium  inllltrated  by  cords  of  eells:  /,  dermal  tissue  intlUratvd  Willi  liacilli 
and  cells;  <j,  bloody  exudate  containing  bacilli,  lvin<?  uixm  the  surface;  /i,  liuir-fcillicle ;  /,  swcat-jrland. 
X33. 


exudate  as  well  as  by  bacilli.  The  bacilli  lie  particularly  in  the  outer 
portions  of  the  eorium  (dj  and  in  the  papillaiy  l)ody  (c),  but  may  also 
penetrate  into  the  deeper  layers  of  the  eorium  (/).  In  the  neighborhood 
of  the  papillary  body  (c)  the  exudate  is  sanguineous.  A'^esicles  tilled 
with  bloody  fluidresult  if  the  exudate  extendsup  to  the  epithelial  covjm' 
ing,  and  if  the  deeper  portions  of  the  latter  become  litpietied,  thereby 
permitting  the  lifting-up  of  the  superficial  layeis  by  tin'  exuded  lluid. 
If  the  upper  layers  of  the  skin  are  also  lost,  the  bloody  liuid  (•ontainin;- 
the  bacilli  (g)  appears  upon  the  surface. 

The  cellular  infiltration  has  its  seat  chiefly  in  the  eorium  {<!,  d^,  <■), 
and  the  impression  is  obtained  as  if  the  great  massing  of  cells  foiined  ;t 
certain 
of  the  b: 

for  the  greater  part  to  the  polynuclear  leuco-  '^  ,XV"^i.  A  '\  ^'^  ^^ 
cytes  (Fig.  4.54).  The  bacilli  lie  sometimes  ''  v)  ,\^J  \_  ^*l 
in,  sometimes  between  the  cells.  1^     ^    ^  \ 

If  an  infection  with  anthrax-spores  takes  '' 
place  in  the  intestinal  canal,  an  event  which 
occurs  most  frequently  in  the  small  intestine, 
less  often  in  the  stomach  and  huge  intestine, 
there  develop  dark-red  or  brownish-red  luem- 
orrhagic  foci,  the  size  of  a  lentil  or  bean  or 


'kk^y^- 


Fl(i.  4.'>4.— Portion  of  thcnnthnix 
pustule  fntm  the  arm  <KI^'.  4&i), 
coMtalnlnjf  bacilli.     >,  :«•. 


592  THE    PATHOGENIC    FISSION-FUNGI. 

larger,  with  a  grayish-yellow  or  greenish-yellow,  discolored  slough  iii 
the  centre.  In  other  cases  the  crests  of  the  folds  of  the  mucosa  are 
swollen  and  hieniorrhagic,  and  show  evidences  of  sloughing  in  the  most 
prominent  paj'ts.  The  mucosa  and  submucosa  are  iufiltrated  with  blood 
iu  the  region  of  the  foci ;  the  surrounding  tissues  are  cedematous  and 
hypera?mic.  Bacilli  are  found  in  the  tissues  both  in  and  about  the  foci, 
particularly  in  the  blood-  and  lymph-vessels,  and  they  may  also  be 
demonstrated  in  the  neighboring  iymph-glands. 

Primary  lung  infection  may  also  occur  in  man  as  the  result  of  the 
iidialation  of  anthrax-spores,  pi-oving  fatal  in  from  two  to  seven  days, 
individuals  who  have  to  handle  the  hair  of  animals  that  have  died  of 
anthrax  are  especially  exposed  to  infection ;  and  the  disease  known  as  rag- 
sorter^s  disease,  which  occurs  in  men  and  women  employed  in  the  sorting 
of  rags  in  paper-factories,  is  in  a  part  of  the  cases  nothing  more  than  an 
anthrax  infection.  The  spores  taken  into  the  lungs  in  the  respired  air 
develop  in  the  bronchi  (rarely  in  nose  [E5sel] )  and  alveoli,  in  the  lymph- 
spaces  of  the  lungs  and  pleura  and  in  the  bronchial  glands,  and  penetrate 
also  into  the  A^essels.  Their  growth  causes  intiammatory  hsemorrhagic 
processes  in  the  lungs,  as  well  as  serous  hfcniorrhagic  exudations  into  the 
pleural  cavity  and  the  mediastinal  tissue,  and  swellings  of  the  lymph- 
glands.  It  may  also  lead  to  the  production  of  necrotic  foci  in  the  lungs 
and  in  the  bronchial  and  tracheal  mucosa. 

Mice,  rabbits,  sheep,  horses,  and  sparrows  are  very  susceptible  to  an- 
thrax ;  white  rats,  dogs,  and  Algerian  sheep  are  less  susceptible  or  im- 
mune. Cattle  are  easily  infected  through  the  taking  in  of  the  spores 
from  the  alimentary  canal,  but  are  less  susceptible  to  inoculation.  Forma- 
tion of  spores  does  not  take  place  in  the  tissues  and  in  the  blood. 

According  to  Brefeld,  Prazmowski,  Klein,  and  others,  the  spore  consists  of  a 
protoplasmic  centre,  which  is  enclosed  by  a  double  membrane,  the  exosporiimi  and  the 
endosporium.  During  germination  the  former  is  ruptured,  the  latter  becomes  the 
membrane  of  the  embryo.     The  liberated  embryo  multiplies  by  division. 

Swarming  movements  are  not  seen  throughout  the  entire  jjeriod  of  development; 
the  bacilli  are  always  motionless. 

The  bacilli  of  anthrax  are  easily  killed  by  high  temperatures,  drying,  and  through 
the  decomposition  of  the  nutrient  fluid.     The  spores,  on  the  other  hand,  are  veiy  re-  I 
sistant,  and  are  tlierefore  usually  the  medium  of  the  spread  of  the  disease.  ! 

The  colonies  upon  gelatin  show  a  wavy,  irregularly  shaped  margin,  and  consist  of  i 
many  interlacing  strands  of  threads,  which  later  grow  out  of  the  culture  in  all  dirof- 
tions.     The  gelatin  is  liquefied   im.mediately  about  the  culture.     On  potato  the  bacil- 
lus forms  grayish-white,  slightly  granular  colonies  having  a  sharply  outlined  bordtr. 
On  blood-serum  it  forms  a  white  coating. 

Stab-cultures  in  gelatin  are  white  and  during  the  process  of  growth  they  radiate 
at  right  angles  from  the  line  of  inoculation  out  into  the  gelatin,  particularly  near  tlic 
surface.     After  liquefaction  of  the  gelatin  they  sink  to  the  bottom. 

A  marked  attenuation  of  anthrax-bacilli  may  be  produced  by  keeping  the  bacilli 
for  ten  minutes  at  a  temperature  of  55°  C.  (Tous.<<aint)  or  for  fifteen  minutes  at  52°  (  .. 
or  for  twenty  minutes  at  50°  (1.  (Chnuveau),  or  fin-tlier  through  the  influence  of  oxygen  , 
under  high  pressure  (Chauveuii).     The  bacilli  attenuated  by  exposure  for  a  short  time  . 
to  high  temperatures  (iui(;kly  regain  their  virulence;  those  attenuated  at  lower  tern    , 
l)eratures  remain  weaivcned  for  inaiiv  ueiicrations. 

The  addition  of  carbolic  acid  to'the  nutrient  fluid  in  a  proportion  of  1:G00  permits 
tlie  furtlier  developnicnt  of  antluax  l)acilli,  but  destroys  their  virulence  within  twenty- 
nine  days  {Vhdinheiiaitd,  Roiu).  Ijikewise,  an  attenuation  may  be  produced  by  the 
aildition"  of  potassium  biciiromate  (1 :  2,000-1 : 5,000).  The  addition  of  carbolic  acid  up 
to  1:  800  hinders  al  tiie  same  time  the  formation  of  spores. 

Through  cultivation  of  the  bacilli  at  42-43"  C.  {Ihvssaint,  Pasteur,  Koch)  their  J 
virulence  may  be  so  weakened  that  they  no  longer  kill  first  sheep,  then  rabbits  and  j 
guinea-pigs,  and  finally  mice.  If  the  temperature  is  kept  in  the  neighborhood  of  43°  C.  \ 
this  result  may  l)e  obtained  in  six  days;  at  42°  C.  it  may  require  about  thirty  days  to 


i 


ANTHRAX.  rM\ 

decrease  tlie  virulence  to  tliis  extent  (K<>rh).  l?y  fust  inoculating  with  bacilli  wliicli 
kill  mice  but  are  harmless  for  guinea-pigs,  and  afterward  inoculating  with  bacilli  wiiicli 
kill  guinea-pigs  but  not  strong  rabbits,  an  ininiiniily  against  anthrax  may  be  obtained 
in  sheep  and  cattle  but  not  in  the  case  of  mice,  guin"capigs,  and  rabbits.  Such  protec- 
tive inoculations  are,  however,  not  of  ]>ractical  value,  since,  in  order  to  jirotect  against 
natural  infection  with  spores  from  the  intestinal  canal,  sucii  virulent  inoculalion-mate- 
rial  must  be  used  that  a  large  i)er  cent,  of  sheep  (ten  to  litteen  per  cent.)  die  from  the 
inoculations.  Further,  the  protection  alTorded  by  the  inocidations  is  of  very  sliort 
duration,  and  the  inoculation  must  be  repeated  within  a  year's  time. 

According  to  observations  by  7A"/.r  and  ClKniihirli'ind  anthrax  l)acilli  which  are 
cultivated  in  bouillon  to -which  a  small  amount  of  potassium  bichromate  (1 : 'J. tKIO)  or 
carbolic  acid  (1  to  2: 1,000)  has  been  added,  permanently  lose  their  power  of  spore-forma- 
tion wliile  retaining  their  virulence. 

According  to  Koch,  anthrax-bacilli  may  be  cultivated  in  tlie  presence  of  abundance 
of  water  upon  potatoes  and  in  an  alkaline  or  neutral  hay -infusion,  cold  infusions  of  pea- 
straw,  on  mashed  barley  and  mashed  wheat,  in  the  juice  of  turnips,  on  maize,  legumi- 
nous seeds,  and  numerous  dead  plants.  Consequently  they  are  ai)le  to  grow  and 
develop  outside  of  the  animal  bodj^ — for  example,  in  marshy  regions  and  on  river-banks 
{R.  Koch).  The  entrance  into  the  animal  body  is  to  be  regarded  as  an  accidental  excur- 
sion of  ectogenic  bacilli.  According  to  Soijka  the  development  of  s|)ores  takes  place 
very  quickly  in  a  moist  medium  containing  the  necessjiry  nutrient  material  at  tempera- 
tures above  15°  C.  According  to  Kitt  the  dung  of  cattle  forms  a  nutrient  substratum 
for  the  bacilli. 

True  toxins  or  endotoxins  have  not  yet  been  demonstrated  in  the  ca.se  of  anthrax 
bacilli. 

Literature. 

(Bacillus  A  nth  racis. ) 

Bail:    Xatiirl.  u.  kimstl.  Milzbrandimmunitiit.     Cbl.  f.  Bakt.  Orig.,  xxxiii.,  1903. 
Behring:   Beitrage  zur  Aetiologie  des  Milzbrandes.     Zeitschr.  f.  Hyg.,  vi.,  vii.,  18S9. 
V.  Behring  ii.  Mach:    Bez.  der  Bacillen  zu  endothel.  Zellen.     D.  med.  Woch.,  1904. 
Bleuler:   Hautmilzbrand:   Correspbl.  f.  Schweizer  Aerzte,  1SS4. 
Blumer:   Anthrax  Septicaemia.     Bull,  of  Johns  Hopkins  Hosp.,  vi.,  1895. 
Brauell:   Unters.  betreffend  den  Milzbrand.     Virch.  Arch.,  11  Bd.,  1857. 
Buisson:   Charbon  intestinal  chez  rhomme.     Arch,  de  med.  exp.,  i.,  1889. 
Conradi:  Toxinbildung  bei  Milzbrandbakterien.     Z.  f.  Hyg.,  37  Bd.,  1899. 
Czaplewski:  Unters.  lib.  d.  Immiuiitat  d.  Tauben  gegen  Milzbrand.     Zeit.  f.  Hyg., 

xii.,  1893. 
Davaine:    Compt.  rend,  de  I'Acad.  des  sciences,  1863,  1864,  1865,  1868,  1870,  1873. 

Republished  in  L'oeuvre  de  C.  J.  Davaine,  Paris.  ISSO. 
Dittrich:  Prim.  Milzbrandinfection  des  .Magendarmkanales.     Wien.  klin.  Woch.,  1891. 
Eppinger:   Die  Hadernkrankheit,  Jena,  1S94. 

Frank:    Milzbrandimpfung.     Zeitschr.  f.  Thiermed.,  vii.,  Suppl.,  1884. 
Hoffa:  Die  Xatur  des  Milzbrandgiftes,  Wiesbaden,  1886;    Zur  Lehre  d.  Sepsis   u.   d. 

Milzbrandes.     Lan-eubeck's  Arch.,  39  Bd.,  1889. 
Jacobi:   \wr  FiiUe  v.  Milzl)rand  btini  Menschen.     Zeitschr.  f.  klin.  Med.,  17  Bd.,  1890. 
Johne:    Morphologic  der  Milzbrandl)acillen.     Deut.  Zeit.schr.  f.  Thiermed.,  xix.,  1S93. 
Klett:    Sporenbildung  d.  Milzbrandb.  bei  Anaerobiose.     Zeit.  f.   Hyg.,   35  Bd..   1900. 
Koch,  R.:  Beitr.  z.  Biol.  d.  Pfl.  v.  F.  Cohn,  2  Bd.,  p.  272.     .Mittheil.  a.  d.  K.  Gesund- 

heitsamte,  Berlin.  1881.  1884;  Ueber  die  Milzbrandimpfung.  1.SS2. 
Koch,  W.:   Milzbrand  und  Rauschbrand.     Deut.  Chir.,  9  Lief.,  1886. 
Krumbholz:  Darmmilzbrand.     Beitr.  v.  Ziegler,  xvi.,  1894. 
Kurloflf:    Im  Laboratorium  acquirirte  Milzbrandinfection.     Deut.  .\r(h.    f.   kl.  Med., 

xliv.,  1889. 
Lewin:   Milzbrand  beim  Menschen.     Cbl.  f.  Bakt.,  xvi.,  1894. 
Lodge:    La  maladie  des  trieurs  de  laine.     Arch,  de  med.  exp.,  ISOO. 
Lubarsch:   Milzbrand.      Krgel)ii.  d.  allg.  Path.,  v.,  1900. 
Melnikow:    Kunstliclie  Iinmuuitatd.  Kaninchen  geg.  Milzbrand.     Zcit.  f.  Hyg.,  xxv., 

1897. 
Muller:    Der  Milzbrand  der  Ratten.     Fort.schr.   d.  ^h•<l.,  1893;    Aeusserer  .Md/.brand 

des  Men.schen.     Deut.  med.  Woch.,  1894  (Lit.). 
Oppenheimer:   Toxine  u.  Antitoxine.     Jena,  1904,  \).  l.')4. 

Palm:    Histologic  des  iius.seren  Milzi)ramlcarbunkels.     Beitr.  v.  Ziegler,  ii.,   l.S,S8. 
Paltauf:   Aetiologie  d.  Hadernkrankheit.     Wien.  klin.  Woch..  ISSS. 
Parmier:    La  toxine  cliarbonneuse.     Ann.  de  I'lnst.  Pasteur,  IS'.)."). 


594 


THE    PATIIOGIIXIC    FISSTOX-P^UXGI. 


Pasteur:    T.u  vaccination  charbonneuse,  Paris,  1883. 

Pawlowsky:    Verhalten  d.  Milzbrandbacillen  im  Organismus.    Vircli.  Arcli.,  lOS  B<1., 

1SS7. 
Physalix:   Nouv.  rech.  sur  la  maladie  charbonneuse.     Arch,  denied,  exj).,  ill.,  IMtl. 
Pianese:    La  capsula  del  B.  anthracis.     Giorn.  dell'  Assoc,  di  Xat.,  1891. 
Pollender:   Casper's  Vierteljahrsschr.  f.  ger.  u.  off.  Med.,  S  Bd.,  18.)o. 
Preisz:    Studien  iiber  den  Alilzbrandbacillus.     Cbl.  f.  Bakt.  Orig.,  xxxv.,  1904. 
Reinbach:    Zur  Aetiologie  d.  Liuigengangran.     Cbl.  f.  allg.  Path.,  v.,  1894. 
Roloff:    Der  Milzbrand,  Berlin,  1883. 

Roux:    Hactoridie  charbonneuse  asporogene.     Aim.  de  I'lnst.  Pasteur,  iv.,  1888. 
Sobernheim:  Milzbrand.     Handb.  d.  path.  Mikroorg.,  ii.,  1903. 
Stravis:    Cas  de  charbon  mortel.     Arch,  de  pliys.,  i.,  1883;    Contrib.  a  I'anat.  pathol. 

dc  la  pustule  maligne.     Ann.  de  I'lnst.  Pasteur,  i.,  1887. 
Toepper:    Die  neueren  Erfahrungen  id),  d.  Aetiol.  des  Milzbrandes,  .lena.  1S83. 
Toussaint:    Rech.  experimentales  sur  la  maladie  charbonneuse,  Paris,  1889. 
Wagner:    Le  charbon  des  poules.     Ann.  de  I'lnst.  Pasteur,  iv.,  1890. 
Werigo:    Developp.  du  charbon  chez  le  lapin.     Ann.  de  I'lnst.  Pasteur,  1894. 
Zdrkendorfer :   Damimilzbrand.     Prag.  meil.  Woch.,  1894. 


J^  l.yj.  The  Bacillus  typhi  abdominalis  (Fig.  455),  or  the  Barten'um 
ti/phi,  is  a  lissioii  fungus  which  occurs  chiefly  iu  the  form  of  phinip  rods 
2  to  o  //  loug',haviug  rounded  ends,  and  in  cultui'es  growing  also  iu  pseudo- 
threads.     It  is  regarded  as  the  cause  of  ti/phoid  fever.     Wheu  examined 


FIG.  455. 
Fig.  455.— 'l'yplii)iU-l)a<;'iUi  from 
Fig.  45fi.-T.vpli()i(i-b 


)uie  L-ulture.    i^treak-ini 
ith  tIaL'Plla.     i  After  Biinpre.) 


Fic.  4:)t). 
ulioii  imetliylc 


ali\  e  in  cultures  it  sliows  llveh/  independent  nu>i:enienf,s  wliich  are  accom- 
plisiied  by  means  of  tlagelhx  (Fig.  45G)  attach«Hl  to  the  sides  of  the  rods 
as  well  as  to  their  ends.  The  flagella.  may  be  demonstrated  by  proper 
staining-methods. 

The  bacilli  gain  entrance  into  the  human  onjunisni  througli  the  drinking- 
water  and  food;  though  infection  through  tlie lungs  is  not  to  l)e excluded. 
According  to  the  results  of  anatomical  investigations,  they  develoj)  i)ar- 
licularly  in  the  intestinal  wall,  in  the  ^oVdarji  and  (if/niin(ded  follieles  of  (lie 
.sin(dl  and  laif/e  inte.siinrs,  as  well  as  in  the  me.smterie  /i/nij>li-!/l(inds  and  iu 
I  he  spleen.  In  the  lirst  -named  ])lace  they  cause  an  inpanunatori/  injill ration 
of  the  mucosa  and  smhmueosa  (Fig.  457,  «,,  />,)  which  is  extraordinarilj'^ 
rich  in  cells  and  api)ears  in  the  form  of  flat  or  somewhat  rounded  eleva- 
1  ions  projecting  above  tlie  inner  .sui-face  of  the  intestines.  An  exudation  of 
libiin  in  the  form  of  thi'eads  jnay  take  place  Ix 


on  the  free  surface  and 


TVIMIOII)     KKVKK.  .")<l") 

in  the  deeper  layers.  Oocasionally  cellular  intlaniiiiaioi y  loci  of  limilcd 
extent  also  occur  ill  the  muscularis  (r,,  </,)  and  llic  scrdsn  (<).  A  pail 
of  the  intiltrated  tissue  usually  sl»»u,ulis  and  islhcn  cnst  uiT.  snilml  ulcers 
are  foi'iiied.  In  other  parts  tlie  iiitil1ra1i<.n  iiia\  in-  aitsoihed  and  the 
swel  1  i iig  d i sa ppea r. 

The  sirrlliiiff  of  the  li/iiiph -(/!<(  nils,  Avliich  is  likewise  caused  l.y  :)ii  accu- 
mulation of  cells  and  lluid,  and  occasicnially  <»r  liltrin,  cuds  eillicr  in 
healing  throuoh  the  absorjition  of  the  infiltrite  or  may  also  lead  lo  a. 
partial  necrosis  of  tissue.  In  the  .spleni  the  pulp  iu  |»ai-ticular  swells. 
while  its  vessels  are  greatly  dilated  with  blood,  aud  ilu-  pareitcliyuia  lalci- 
becomes  crowded  full  of  cells  and  tluid. 

The  haoiJli  are  usnaJIji  distrihiilrtl  f/noiif/lioiil  ol/irr  jtmls  -,/'  Ihc  hn«/i/. 
and  it  is  probable  that  tlie  iuHaiuiiiatcuy  exudations  iu  Ihe  lungs  occur- 
ling  at  times  during  the  course  of  typhoid  fever  are  due  iu  ]»ait  loan  in- 


Fi(i.  457— T>plioi(l  fo\(T     scuioii  tliKni, 
brown),    a.  Mucosa  ;/>,  subniiK  osa    <,  iiiusc 
it),  f,,  (llfftTcnt  lavei'.of  the  inti  Min.il  w.ill  sli   u  iiiL'  iiilllti  it 
follicle.     >   1") 


tilirt    of  d  swollen    I'eyer's  |>iiteli  (alcolinl. 

iit(iii<i,  (/,  inusciilaris  externa;  <,  >er()sa: 

f,  sections  of  L'lail.lsof   I.iel.ei 


Kisiiiuivk 
'i.  ''i,  <■,. 
kiihn;  y. 


crease  of  the  bacilli  within  the  lungs.     It  should  alwa\s  be  b(»riie  iu  uiiud 

that  aspiration-pneumonias  are  of  very  fie([uent  occunence  in  the  lungs 

of  typhoid  patients,  and  also  tliat  .sceondniji  iiif ret  ions  (coccij  may  lake 

])lace  from  the  ulcers  and  may  give  rise  to  metastatic  iullammatituis  iu 

1    tlift'erent  tissues.     The  swellings  of  the  mucosa  and  siibnr.icosa  aud  of  the 

!    perichondria!  tissue,  which  often  occur  in  tht^  jialale,  throat,  and  larynx. 

;    are  in  part  the  result  of  the  specilic  infection,  aud  iu  part  of  sccomlaiN 

i    disease.     Moreover,  tyi)hoid-bacilli  have  been  deiiioustialed  iu  llie  ltlt»od, 

i    liver,  gall-bladder,  in  the  rose-spots  of  the  skin,  in  the  kidnexs.  central 

I    nervous  system, testicles,  in  pleuritic  and  ])eritoneal  lluids,  iu  the  perios 

teum,  bone-marrow,  etc.,  in   part  l)y  means  of  the  microscope  aud  iu  i)ai  I 

by  means  of  cultivation.     In  all  of  these  regions  they  may  cause  degen- 

I    eratiou  and  inflammation,  and  give  rise  to  supi)urat  ion,  sothal  the  intlain 

i    niatious  occurring  during  the  course  of  typhoid  fexcr  owe  their  «uigiii 

sometimes  to  the  dissemiiiati<m  and  localization   of  the  typhoid-Itacilii. 

and  sometimes  to  secoudarv  or  mixed  infections.     'I'he   hacilli   circnliii.' 


596  THE    PATHOGENIC    FISSION-FUNGI. 

ill  the  blood  for  about  two  or  three  weeks  aud  their  cultivation  from  the 
l)lood  may  be  employed  as  a  diagnostic  method.     When  typhoid  fever  • 
occurs  during  j)reguancy  tlie  typhoid-bacilli  may  pass  into  the  foetus.         .. 
The  typhoid-bacilli  produce  x>olsons  clinging  to  the  cells  (tgphotoxin),.  | 
aud  but  little  is  known  of  their  nature.     The  symptoms  of  the  disease  are  % 
for  the  greater  part  to  be  referred  to  the  intoxication.     In  the  course  of  \. 
typhoid  fever  there  appear  in  the  blood  certain  bactericidal  substances  j' 
which  cause  a  degeneration  of  typhoid-bacilli  (cf.  §  31).     This  may  be 
demonstrated  by  the  fact  that  (Widal-Gruber  reaction),  through  the  ad- 
dition of  serum  from  an  individual  ill  or  convalescent  from  typhoid  fever, 
to  a  bouillon-culture  of  freely  motile  typhoid-bacilli,  the  latter  become  \: 
motionless,  clump  together  (agglutination),  sink  to  the  bottom  and  die. 
This  reaction  may  be  used  as  a  means  of  diagnosis,  but  is  not  of  absolute 
certainty,  since  agglutination  may  be  produced  by  the  serum  of  Individ-  % 
uals  who  have  not  had  typhoid  fever,  and  may  be  absent  in  the  case  of 
typhoid.     The  agglutinating  power  can  last  for  years,  but  it  may  also  \\ 
vanish  after  a  month  (Krause).  I 

Individuals  who  have  had   typhoid  fever  may  harbor  the    bacilli  within  their  • 
bodies  for  years  after  the  attack,  without  showing  any  symptoms  of  infection  {'Hyjilwid 
mrriers  ").     By  giving  off  the  bacilli  through  their  urine  or  faeces  such  typhoid  carriers 
become  an  element  of  danger  to  the  community  in  which  they  live.     ("  Typhoid  Bacilli 
Carriers."     Park,  J.  Amer.  Med.  Assoc,  1908.) 

The  typhoid^bacillus  stains  well  in  cover-glass  preparations,  with  gentian-violet, 
alkaline  methylcne-blue,  and  Bismarck  brown.  It  is  decolorized  by  Gram's  method. 
It  is  difficult  to  demonstrate  it  in  sections  of  hardened  tissues,  since  the  cell-nuclei  also 
take  the  stain,  aud  because  the  bacilli  are  not  uniformly  distributed,  but  are  usually 
found  lying  in  the  tissue  in  clumps. 

The  bacillus  may  be  cultivated  upon  nutrient  gelatin,  agar-agar,  and  blood- 
serum,  also  in  milk,  and  upon  potato.  Upon  the  last  named  it  forms  a  coating  which 
can  be  scarcely  recognized  by  the  naked  eye;  but  when  the  surface  is  touched  with  a 
platinum  wire  it  becomes  apparent  that  it  is  covered  with  a  pellicle,  which  on  micro- 
scopic examination  is  shown  to  consist  of  bacilli. 

On  gelatin  and  agar-agar  the  bacilli  form  grayish-white,  irregularly  shaped,  fiat 
growths.  Gelatin  is  not  liquefied.  Milk  in  which  the  bacilli  are  grown  is  not  changed 
externally. 

The  cultures  thrive  at  room-temperature  as  well  as  at  body  temperature.  Potato- 
cultures  made  in  the  usual  manner,  when  kept  between  30°  and  42°  C,  produce  rods 
which  have  glistening  bodies  in  their  poles.  Gaffky  regarded  these  as  spores,  and  the 
majority  of  authors  formerly  accepted  this  view.  According  to  Buchner  and  Pfuhl, 
however,  these  granules  at  the  poles  are  degeneration  jihenomena,  which  occur  par- 
ticularly when  acid  is  present  in  the  culture  medium.  The  polar  granules  represent 
condensed  protoplasm,  and  therefore  stain  in  fresh  preparations  more  quickly  with  the 
aniline  dyes  than  do  the  other  parts  of  the  cell.  The  clear,  colorless  spots  which  are  : 
sci'ii  at  the  ends  of  the  rods  in  dried  and  stained  bacilh  have  been  held  to  be  identical 
witli  the  polar  granules  and  tiierefore  retiarded  as  spores,  but  are  due,  according  to 
liiirlinrr,  to  hollow  spaces  formed  at  tlie  ends  of  the  rods  as  the  residt  of  the  retrac- 
tion of  the  protoplasmic  tube  following  the  death  and  drying  of  the  bacilli.  Spore-  : 
formation  has,  therefore,  not  yet  been  demonstrated. 

Cultures  of  typhoid-bacillus  shuw  few  characteristic  appearances  and  are  with  dif- 
ficulty distinguislied  from  those  of  other  bacteria  widely  scattered  in  the  outer  worhl.  i 
Likewise  their  i)roperties  are  very  similar  to  those  of  the  Bacillus  coli  communis 
(§  l(K)).  Certain  points  of  difference  are  as  follows:  The  typhoid-ljacilli  produce  no 
iudol,  while  other  similar  bacteria,  such  as  the  Bacillus  c:Ai,  produce  it,  so  that  bouil- 
lon cultures  become  red  through  the  addition  of  potassium  nitrite  and  sulphuric  acid. 
'Ilie  typhoid-bacillus  produces  no  gas  in  a  t  vvo-per-cent  grape-sugar  bouillon,  while  the 
Bacillus  coli  produces  gas.  Finally  typhoid-bacilli  in  milk  cause  a  weak  acidity  but 
no  coagulation,  while  the  J5«c///».s  coZi  will  cause  at  37°  C,  even  in  twenty- four  to  forty-; 
eight  hours,  a  strong  acidity  and  coagulation  of  the  milk.  When  typhoid  bacilli  are 
grown  on  agar  colored  blue  with  litmus,  the  color  remains  unchanged,  while  Bacillus 
coli  decolorizes  the  blue  nutrient  medium. 

In  moist  earth  {Grancher,  Deschamps),  in  pure  and  impure  water,  typhoid-bacilli 
may  remain  alive  for  weeks.     In  artificial  Seltzer  water  they  do  not   die  out    for    a 


TYPHOID    AM)    I'AHArvl'IIOIl)     HACII.I.I.  597 

longer  period  (Hochstelicr).  In  privy  vaults  and  fircal  masses,  or  in  earth  saturated 
with  fsecal  matter  {Finklcr,  Uffelmann,  Karlinski)  they  may  under  certain  conilitions 
live  for  weeks  and  months. 

Inoculations  of  the  bacilli  in  the  case  of  the  animals  ordinarily  used  for  exi)cri- 
ment  do  not  produce  a  disease  correspondinjj;  to  typlioid  fever  in  man.  Experimental 
investigations  show,  however,  tliat  tlie  typhoid-bacilH  ])r()duce  active  toxins  (endo- 
toxins?) which  in  large  doses  kill  tlie  animals,  causing  iivpcra-mia  and  swelling  of  tho 
intestinal  follicles,  mesenteric  glands,  and  the  spleen.'  CuHures  injected  into  the 
tissues  cause  a  local  infhinuuatiou  of  greater  or  less  intensity. 

The  value  of  the  agglutination  "test  is  but  limited,  .since  it  is  hard  to  decide 
whether  the  agglutinating efTect  of  the  serum  is  brought  out  by  tiie  same  kind  of  bacil- 
lus or  by  a  related  variety.  In  general  the  .serum  of  a  patient'  agglutinates  tiie  species 
causing  the  disease  in  a  greater  dilution  than  in  the  case  of  a  related  organism,  but 
there  occur  exceptions  to  tliis  rule.  According  to  Liibowski  and  :^lcinberq  the  agglu- 
tinatibility  of  typhoid-bacilli  can  be  easily  increased  in  guinea-pigs  and  rabbits  tlirougii 
a  proteus  or  stapliylococcus  infection.  Much  more  positive  as  a  diagno,stic  method  is 
the  demonstration  of  typhoid-bacilli  in  the  blood  by  means  of  cultures. 

As  paratyphoid  fever  there  has  been  differentiated  through  observations  of 
recent  years  a  disease  similar  to  ordinary  typhoid  fever,  but  wliich  is  caused  by  a 
special  form  of  bacillus  of  which  a  type  A  and  a  type  B  have  been  described.  Cl'ini- 
cally  the  disease  runs  a  lighter  course  than  typhoid  fever  and  rarely  is  fatal.  Tlie 
anatomical  findings  {Longcope  and  Luksch)  are  similar  to  those  of  typhoid  fever,  Init 
the  intestinal  changes  arc  less  marked  and  ordinarily  confined  to  the 'colon.  It  is  po.s- 
sible  to  make  a  differential  diagnosis  by  means  of  the  Widal  reaction:  yet  it  sliould 
be  noted  that  paratyplioid  serum  will  agglutinate  also  typhoid-bacilli  'to  a  certain 
degree. 

The  paratyphoid  bacteria  stand,  as  far  as  their  cultural  characteristics  are  con- 
cerned, between  tlie  typ!u)id-l)acillus  and  the  Bacillus  coli  communis.  The  round, 
smooth-edged  gelatin  colonies  (Kayser)  of  freshly  cultivated  .strains  do  not  sliow  tlie 
superficial  vein-like  furrowing.  In  the  type  A  they  are  almost  colorless,  while  in  tlie 
type  B  they  are  whitish.  Both  consist  of  short  rods  and  are  lively  motile;  they  fer- 
ment sugar  without  coagulating  milk;  cause  fluorescence  in  neutral-red  media;  grow 
as  blue  colonies  on  the  Drigalski-Conradi  plates  and  do  nf)t  pro(hice  iiulol  in  bouillon 
cultures.  Type  A  forms  more  delicate  pellicles  than  B.  and  grows  on  potatoes  in  a 
manner  similar  to  the  bacillus  of  typhoid  fever.  Milk  is  not  changed  l>y  type  A,  while 
it  is  cleared  (alkaline)  after  several  weeks  by  type  B. 

Literature. 

(Bacillus  of  Tjiphoid  Fcm:) 

Arustamoff:    Zur  Fraije  iib.  d.  Entstehunsi  d.  tvplioseii  Piieumoiiie.     Ch\.  f.   l^akt., 

iv.,  1,S89. 
Brieger:   Spez.  wirk.  Substanz  d.  Typhu.sbacillen.     D.  med.  Woeli..  1 !»()!'. 
Buchner:    Ueber  die  vermeintl.  Sporen  der  Typhusl)acillen.     Cbl.  f.  Bakt.,  iv.,  ISSS. 
Bunge:  Zur  Kenntni.ss  der  gei.s.seltragenden  Bakterien.     Fortschr.  d.  .Met!.,  xii.,  1894. 
Chantemesse  et  Widal:   Bacille  tvphiquc.     Arcli.  de  phys.,  ix.,  1887;  Ann,  de  rin.st. 

Past.,  1892. 
Chiari:  Cholecvstitis  tvphosa.     Prac  med.  Woch.,  1893;   Zeit.  f.  Heilk.,  xv..  1894. 
Clemens:  Para'typhus.'    C.  f.  Bakt.  l)rig.,  xxxi.,  u.  D.  med.  Woch..  1904  (Lit.). 
Coleman  and  Buxton:    Paratyphoid  infections.     Amer.  .Jour,  of  .Med.  Sc,  19UL'. 
Cyg-naus:   Studien  iiber  den  Typhusbacillus.     Beitr.  v.  Ziegler,  vii.,  1X90. 
Dmochowski  u.  Janowski:    Eiterung  erreg.  Wirkungd.  Typhusbacillus.     Beit  r.  v. 

Ziei,der,  xvii..  ISO.')  (Lit.). 
Ebermaier:   Knochenerkrankungen  bei  Typhus.     Deut.  Arch.  f.  kiln.  .Med.,    11    Bd., 

1S,S9. 
Eberth:    Vich.  Arch.,  81  Bd.;    Samml.  klin.  Vortr.,  No.  \2(\:    Ceht  <ler  'ly|iliuslKi<'i!- 

lus  auf  den  Fotus  liber?     Fort.schr.  d.  Med.,  vii..  1889. 
Faulhaber:   Bakterien  in  d.  Nieren  bei  acuten  Infectionskranklieiten.     Beit.  v.  Zieg- 
ler. X.,  1891. 
Fischer:   Werth  der  Widal'schen  Reaction.     Zcitschr.  f.  Ilyg..  :!_'  lid..  ls9'.i. 
Flexner:   Certain  Forms  of  Infection  in  Typhoid  Fever.     .lolms  Hopkins  Hosp.   I!e|>., 

v.,   1895;  Unu.sual  Forms  of  Infection  with  the  Typhoid   Bacillus,   etc     .lolms 

Hopkins  Hosp.  Rep.,  1900. 
Forster:    Baktericide  Wirkunti;  d.  Blutsenmis  v.  Tvphuskranken.     Zeif>elir.  f.   ilyg., 

xxiv.,  1897  (Lit.). 


59S  ^J'llE    PATHOGENIC    FISSION -irxGi. 

Frankel,  E.:  Complication  v.  Abdominaltji^lui.s.     Jahresber.    d.    Hamburg.     Kran- 

kenanst..  i.,  IN'.K):    Roseola  typhosa.     Zeitschr.  f.  Hyg..  34  Bd.,  1900;  Erkrank. 

d.  KnoclK'Hiuarks.     .Mitteil.  a.  d.  Grenzgebieten.  xi..  1903. 
Frankel,  E.,  u.  Simmonds:  Die  atiologische  Bedeutung  d.  Typhusbacillen,  Leipzig, 

ISSd. 
Fiix-brmger:   Ahdominaltyiihus.     Eulenburgs  Jahrb..  ii..  1904. 
Gaffky:  Aetiologic  d.  AlxlOiniiialtviiluis.     Mittlieil.  a.  d.  K.  Gesuiidheitsamte,   Berlin, 

1SS4. 
Gasser:    Le  baeillo  typlii(iue.     Arch,  de  med.  exp.,  iii.,  1891. 

Germano  u.  Maurea:   Typhusbac.  u.  ahnliche  Bakterien.     Beitr.  v.  Ziegler,  xii.,  1893. 
Grancher  et  Deschamps;  Le  bacille  typhique  dans  le  sol.     Arch,  de  med.  exp.,  i., 

1889. 
Hamilton:   The  Ply  as  a  Carrier  of  Typhoid.     Jour,  of  Amer.  Med.  Ass.,  1903. 
Hesse:  Unsere  Nahrungsmittel  als  Nahrboden  f.  Typhus  u.  Cholera.     Zeitschr.    f^ 

Hyg.,  v.,  1889. 
Hiss:   Studies  in  the  Bacteriologj'  of  Tj^jhoid  Fever,  etc.     Med.  News,  1901:    New 

and  Simple  Media  for  the  Differentiation  of  the  Colonies  of  Typhoid,  Colon,  and 

Allied  Bacilh.     Jour,  of  Med.  Res.,  1902. 
Hodenpyl:   On  the  Occurrence  of  Typhoid  Fever  without  Characteristic  Lesions  of  the 

Small  Intestine.     Stud,  from  Dept.  of  Path,  of  Columbia  LTniversity,  1897-98. 
Holz:    Exp.  Enters,  lib.  d.  Nachweis  d.  Typhusbacillen.     Zeitsch.  f.  Hyg.,  viii..  1890. 
Janowski:    Zur  Biologie  d.  Typhusbacillen.     Cbl.  f.  Bakt.,  viii.,  1890. 
Jatta:    Agglutination  d.  Tvphusbacillus  u.  d.  Colibacillen.     Zeitschr.  f.  Hvg.,  33  Bd., 

1900  (Lit.). 
Jolinston:   Paratyphoid  Fever.     Amer.  Jour,  of  Med.  Sc,  1902. 
Karlinski:  Typhusbacillen  in  typhjsen  Dejectionen.     Cbl.  f.  Bakt.,  A-i.,  1889. 
"Kayser:  Paratyphus.     C.  f.  B.,'Orig.,  xxxv.,  1904.  u.  D.  med.  Woch.,  1903  (Lit.). 
Kitasato:    Verli.  d.  Typhusbacillus  zu  saure-  u.  alkalihalticen  Nahrboden.     Zeitschr. 

f.  Hyg.,  iii.,  1888. 
Klebs:   Bacillen  im  Typhusdarm.     Arch.  f.  exp.  Path.,  xii.,  xiii..  xv..  18.S()-S2. 
Krause:    Dauer  d.  Bestehens  d.  Widalschen  Probe.     C.  f.  Bakr.  Orig..  xxxvi..  1904. 
Lubowski  u.  Steinberg-:   Agglutination.     D.  A.  f.  Idin.  Med.,  79  Bd.,  1904. 
Luksch:    Paratyphus.     Cbl.  f.  Bakt.,  Orig.,  xxxiv.,  1903. 
Mallory:    Histological  Study  of  Typhoid  Fever.     Jour,  of  Exj).  Med.,  1898. 
Meisels:    Uebcr  das  Vorkommen  von  Tyi^husbacillen  im  Blutc.     Wioii.  med.  A\'(ich., 

1886. 
Neufeld:   Typhus.     Handb.  d.  path.  Mikroorg..  ii.,  Jena.  1903. 
Neuhauss:    Nachweis  d.  Typhusbacillen  am  Lebenden  (in  Roseolaflecken ).     Berl.  kl. 

Woch.,  1886. 
Neumann:   I'^eber  Typhusbacillen  im  Urin.     Berl.  klin.  '\\'och..  1890. 
Oppenheimer:   Toxine  und  Antitoxine,  Jena,  1904,  p.  135. 
Orloff:    Aetioloirie  der  d.  Tvphus  abdom.  complicirt.  Eiteruniien.     Cbl.   f.    Bakt..  viii., 

1890. 
Osier,  Flexner,  Blumer,  Reed  and  Parsons:    Studies  in  Tvpiioid  Fever.     J.   Hop. 

Hosp.  Rep.,  v.,  189,1. 
Petruschki:    Ausscheidung  d.  Typhusbacillen  durch  Urin.     Cbl.  f.  Bakt.,  xdii.,  1898. 
PfeifPer  u.  Kolle:   Spec.    Inmimitatsreaction  d.    Tvphusbacillen.     Zeitschr.    f.  Hvg., 

xxi.,  1.S96. 
Quincke:    Zur  Pathologie  des  Abdominaltvphus.     Berl.  klin.  Woch..  1894. 
Rodet:   Agglutin.  du  bac.  d'Eberth  et  du  B.  coli.     Jour,  de  phys.,  i>.,  1900. 
Sirotinin:    Die    Febertragimg   v.    Tvphusbacillen    auf    Versuelisthiero.     Zeitschr.    f. 

Hyg..  i.,  1886. 
Stern:    Wert  der  Agglutination,     lierl.  klin.  AVocli.,   lOO.l. 

Stern  u.  Korte:    Baktericide  lieaktion  v.  Bhitserum.     Berl.  kUii.  AVuch..  1904. 
Thayer:    Observations  on  the  Jilood  in  Tvphoid  Fever.     Johns  Hopkins  Hospital  Re- 
port, 1901. 
Tictine:    Meningitis  et  abces  jiroduits  par  le  l)ncillc  de  la  fievre  tvph.     Arch,  de  med. 

.xp.,  1894. 
Uffelmann:    Lebensfahi-keit  d.  Tviilms-  U:  Cli(.lcral)acillen  in   Facahnassen.     Clil.  f. 

15a kt..  v.,  1889. 
Widal  et  Sicard:    Lc  serodiagnostic     Ann.  de  I'lnst.  Pasteur,  1897  (Lit.). 
Winterberg-:  Typluis-Agglutinin.     Zeitschr.  f.  Hyg.,  32  Bd..  1S99. 

§!()(►.  Till'  Bacillus  coli  communis  or  Ihe  lUtcfniidii  coli  roinmune 
(Eschericli)  is  ;i  lission-fmi^us  wliicli  is  oon.stantly  prosent  in  the  iutes- 
liiiiil  tiact  of  iiuiM  as  Avell  as  of  tlie  luamnialia.     The  bacilli  are  rods  2-3  ii 


h>ug  aud  0.3-0.4  //.  thick.  They  an*  luotiU'  and  may  po.ssess  as  many  as 
twenty  liagel  la  on  tnie  rod.  The  bacilli  grow  at  r(»()ni-teni])ei-alur«' as  well 
as  at  the  temperature  of  the  ineubiilor.  They  form  within  the  .m'latin 
small,  round,  white  colonies;  upon  its  surface  iM'llicle  like  coatin.u>. 
Tpou  jxttatoes  they  form  moist  coaliuus  of  tlic  yellow  color  of  mai/c 
or  pt'ase  ((iunther).  They  dt>  not  form  spines;  and  arc  nol  >lained  h.\ 
Gram's  method. 

The  BacillKs  coli  is  very  sinular  lo  the  tyi)lioid  bacillus,  but  may  \n\ 
differentiated  from  it  by  proper  methods  of  cultivation  and  i»>  the  em- 
ployment of  suitable  reactions  (ef.  §  15;)).  It  was  formerI_\-  re<;ai-ded  as 
a  harmless  saprophyte  of  the  colon  ;  but  from  lati'r  in\esti.<;ations  it  can- 
not be  doubled  that  it  also  ])ossesses  ])athoii<'nic  j)roi)eitiesaud  may  cause 
ihyencrafiotis  and  iiiflanuiialions  in  >  arious  tissues.  I  iider  suital)ie  condi 
tious  ( jierf oration  or  incarceration  of  the  intestine,  or  iin])action  of  fa-ces) 
it  may  pass  into  the  iieritoneal  cavity  and  excite  purulent  inllammations. 
or  at  least  take  part  with  other  bacteria  in  the  i)roducti(»u  of  intlamma 
tion.  Further,  it  not  infrequently  gains  access  to  the  bile-j>assages  and 
gall-bladder,  as  Avell  as  to  the  descending  urinary  passages  and  liie  kid- 
neys, giving  rise  to  inflammations  of  varying  intensity.  The  bacillus 
has  also  been  found  in  the  meningeal  exudate  in  certain  cases  of  sepsis; 
it  has  been  demonstrated  also  in  pericarditis,  bronchopneumonia,  stru- 
mitis, angina  of  scarlet-fever,  audit  cannot  be  doubt<'d  llial  it  may  be 
the  cause  of  the  affections  named. 

The  similarity  bet\Yeen  the  tH)l()ii-baciUus  and  tiir  typiH)idd)a<-illus  has  led  \arioiis 
authors  to  assume  that  the  two  hat-ilh  are  only  varieties  of  the  same  speeies,  and  tliat 
the  two  forms  may  pass  over  into  each  other.'  At  the  present  time  the  view  prevail> 
that  the  two  baciU'i  are  to  be  wholly  separatetl  from  each  other  (§  l.')9).  Moreover,  tlie 
form  of  bacillus  wliich  is  describctras  colon-hacilhis  is  not  a  very  distinct  form.  l)Ut  rep- 
resents rather  a  group  of  different  varieties.  Three  to  four  days  after  tl\e  inoculation  <>f 
an  animal  with  colon-bacilli  tlie  blood-serum  of  tlie  infected  animal  produces  an  agsilu- 
tination  of  colon-bacilli  (Jafta).  whicii  is  most  marked  in  the  case  of  that  variety  whicli 
was  used  for  the  inoculation.  Colon-baciUus  serum  (Jutia)  a,i:,dutinates  typhoid-bacilli 
more  markedly  than  does  normal  blood-serum.  On  the  other  hand,  tvplioid  serum 
can  agglutinate  different  varieties  of  coldu-bacilli. 

Literature. 

(Btiri/his    (nil    (oiininnii.s.) 

Ackex-mann:   Les.  osteomyeliticiucs  cxik't.  pr<)\-.  ]>.ir.  I'.ir.  <-oli  cninm.    Ardi.  di-  nu'd. 

exp..  vii..  1S9.'). 
Adami,  Abbott  and  Nicholson:  On  (lie  Diph.c.K-c.id  l'(.nn  ..f  thr  C.lnn  Kacilhi^. 

.Jour,  of  Exp.  -Med..  1S99. 
Allen:    Paracolon  Infection.     Amer.  .Join-,  of  Med.  Sc.  19U;{. 

Arnaud:  Rech.  sur  I'etiologie  de  la  dysenteric.  Ann.  de  I'lnst .  raslcur.  \iii..  Is'.M. 
Bunge:  Zur  Kenntniss  der  geisseltragenden  Bakterien.  Fortsclu-.  d.  .Med..  \n.,  1S91. 
Buxton:   A  Comparative  Studv  of  the  Bacilli  Intermediate  between  B.  ("oh  ("omnuinis 

and  B.  Typhosus.     Jour,  of  Med.  Res..  1902. 
Gushing:  A  ('omi)arative  Studv  of  Some  .MemluMs  of  a  I'athological  (Imup  of  liaciUi 

..f  tiic  Hoii  Cholera  Tvi)e.  fntermediate  betwren  ilic  Typiioi.l  an.l  C..lnn  Croups. 

.lohns  Hopkins  Hosp.'BulL.  1900.      . 
Dunbar:    Cnters.  lib.  Tvpiiusbac.  u.  liact .  c.h.     Zeitsciir.  f.  Ilyg..  \n..   1S9J. 
Escherich  u.  Pfaundler:   Bacti-rium  coh    comniunc      I  land!.,  d.   p.    .Mikmorg..  u., 

19(i:!  (Lit.). 
Ford:    Varieties  of  Colon  Bacilli  Isolated  from  Man.      .Nh-nt.  M.-d.  .h.rn-..   190(1 
Hofmeister:    Zur  Charakteristik  d.  Eklampsiebacillus  (!(  id.-,     iurtschr   d.   M.d..  x.. 

1S92. 
Janowski:    Die  t'rsachen  rler  Kiterimg.     Beitr.  v.  Zir-:i«T.  w..  Is91. 


600  THE    PATHOGENIC    FISSIOX-FIXGI. 

Jatta:  Acglutination  d.  Typhusb.  u.  d.  Organism,  d.  Coligruppe.     Zeitschr.  f.   Hyg., 

32  Bd.,  1900  (Lit.). 
Kamen:  Aetiologie  der  Winckel'schen  Krankheit  (Bac.  coli).     Beitr.  v.  Ziegler,  xiv., 

1S9:;. 
Kiessling:   Das  Bacterium  coli  commime.     Hyg.  Rundschau,  1893. 
de  Klecki:    Pathogenic  de  I'appendicite.     Ann.  de  I'lnst.  Pa.steur,  1899. 
Lartigau:   The  Bacillus  Coli  Communis  in  Human  Infections  (Lit.).     Studies  from  the 

Dept.  of  Path,  of  Columbia  University,  1901-02. 
Lesage  et  Macaigne:   Virulence  du  bact.  coli.     Arch,  de  med.  exp.,  iv.,  1892. 
Libman:    Paracolon  Infection.     Jour,  of  Med.  Res..  1902. 
Longcope:    Paracolon  Infection.     Amer.  Jour,  of  Med.  Sc,  1902. 
Neisser:    L^nters.  iib.  d.  Typhusbac.  u.  Bact.  coli.     Zeitschr.  f.  klin.  Med.,  xv.,  1893. 
Oker-Blom:   Eindringen  des  B.  coli  in  die  Darmwand.     Cbl.  f.  Bakt.,  xv.,  1894. 
Pisenti:  t?ui  rapporti  del  B.  coli  coUa  infezione  tifosa.     Arch.  p.  le  Sc.  Med.,   xviii., 

1S94. 
Renault:   Du  bact.  coli  comm.  dans  I'infection  urinaire.  Paris,  1893. 
Rodet  et  Roux:   Bac.  d'Eberth  et  B.  coh.     Arch,  de  med.  exp.,  iv.,  1892. 
Roger:   Toxicite  des  prod,  solubles' du  bact.  coli.     Arch,  de  phys..  1893. 
Schmidt  u.  Aschoff:    Die  Pyelonephritis  in  anat.  u.  path.  Beziehungu.  die  ursiichl. 

Bedeutung  d.  Bact.  coli  comm.  f.  d.  Erkrankung  der  Harnwege,  Jena,  1893. 
Stern:    Pathogene  Wirkung  des  Colibacillus.     Deut.  med.  Woch.,  1893. 
Stroebe:    Acute  Leberatrophie.     Beitr.  v.  Ziegler.  xxi.,  1897  (Lit.). 
Trambusti:   Zur  Frage  d.  Identitat  d.  Bact.  Eberth  u.  d.  Bact.  coli.    Cbl.  f.  allg.  Path., 

iii.,  1892. 
Wurtz:   Le  bacterium  coli  commune.     Arch,  de  med.  exp.,  v.,  1893. 

§  161.  Uuder  the  desiguatioii  Bacillus  enteritidis  (Ciiirtner)  there  is 
placed  a  group  of  bacilli  found  iu  animals  suffering  with  inflammations 
of  the  intestine,  lungs,  uterus,  or  udder,  and  with  septicaemia.  When 
gaining  entrance  into  the  human  alimentary  tract  these  bacilli  excite 
more  or  less  severe  inflammations  of  the  intestine  characterized  in  part 
by  swellings  of  the  follicles.  Man  is  infected  by  eating  meat  taken  from 
animals  slaughtered  while  in  a  diseased  condition,  and  such  an  infection 
takes  place  most  often  through  the  meat  of  sick  calves.  Other  sources 
of  infection  (drinking-watei-,  milk,  fish  that  have  eaten  diseased  meat, 
oysters,  etc.)  are  not  excluded.  The  affection  belongs  to  the  groui)  of 
meat-poisonings  (see  Bac.  botulinus,  §  157)  occurring  in  different  places 
in  the  form  of  local  epidemics. 

The  bacilli  are  short,  often  ovoid,  at  times  motile,  and  possess  four  to  j) 
twelve  flagella.  They  are  not  stained  by  Gram's.  They  form  poisons 
that  are  resistant  to  high  temperatures;  and  are  pathogenic  for  mice, 
guinea-pigs,  rabbits,  calves,  and  apes.  Injected  into  the  tissue  they  cause 
local  inflaiiiniations  and  give  rise  to  hjematogenous  and  lymphogenous 
metastases  in  different  organs.  Their  entrance  into  the  alimentary  tract 
causes  a  gastro-enteritis. 

The  Bacillus  enteritidis  was  first  studied  by  Gartner  in  1888  and  recognized 
as  tlie  cause  of  the  gastro-intestinal  form  of  meat-poisoning.  His  findings  were  con- 
firmed by  the  investigations  of  Van  Ermengem,  Fischer,  Durham.  Thomassen,  Petri, 
and  others.  The  bacillus  is  distinguished  from  other  bacilU  such  as  the  Bac.  typhi, 
Bac.  coli,  etc.,  partly  by  its  cultural  characteristics  and  also  by  the  agglutinating 
action  of  the  serum  of  infected  individuals  or  of  previously  immunized  experimental 
animals.  Surface  colonies  on  gelatin  are  similar  to  those  of  the  colon-bacillus.  They 
form  no  indol,  do  not  coagulate  milk,  but  cause  it  to  take  on  a  yellow  color:  they 
ferment  sugar  with  the  production  of  gas.  The  infection  is  caused  most  often  through 
the  consumption  of  the  flesh  or  organs  of  calves  and  cattle  that  have  suffered  from  the 
various  diseases  designated  as  septicgemia  of  calves,  dysentery,  enteritis,  pneuino- 
enteritis,  and  infectious  inflammation  of  the  intestine. 

According  to  Tratitmann.  the  bacteria  of  meat-poisoning  and  the  so-called  para- 
typhoid fever  belong  to  the  same  sjjecies,  to  which  he  gives  the  name  Bac.  para- 
typhosus.  The  varieties  of  these  bacilli  can  be  differentiated  only  through  the 
agglutination-test. 


BACILLIS    DYSEXTKHl.i:;    HACILI.l  S    l'Y(  )(■^  A  NKl  S.  (101 

Meat=intoxications  caused  by  the  consumption  of  meat  undergoing  the 
ordinary  putrid  decomposition  caused  hy  liacli  ria  {I'mt,  us.  Ihir.  mli)  air  very  rare 
and  are  not  .severe.  This  i.s  .shown  in  tin-  tact  tliat  ^anie  ami  cheese  are  olleri  eat- 
en in  a  condition  of  decomposition  without  exeitint:  any  marked  gastro-intestiiial 
disturbances  or  symptoms  of  intoxication. 

Literature. 

(Baril/us  Eidn-iiidis.) 

Van  Ermengem:  Fleischvergiftung.    Handb.  d.  jiath.  Mikroorg.,  ii.,  Jena,  liX).')  (bit .). 
Fischer:  Fleischvergiftungen.     Z.  f.  Hyg.,  39  B(b,  1901. 
Gartner:    Fleischvergiftungen  in  Frankenhausen.     Bresl.  arztl.  Z.,   ISS.S. 
Trautmann:   Bac.  d.  Fleischvergiftung  und  des  Paratyphus.  Z.  1'.  Ilyg.,  !.'>  Bd.,  I'.Mi;;. 

§  162,  The  Bacillus  dysenteriae  is  a  Icu-illus  tlcscrilKMl  by  Slii-^a, 
Flexner,  and  Kruse,  and  is  voi y  i)iobal)Iy  tlie  cau.se  of  severe  oalanlial, 
diphtheritic,  hiTemorrhagic,  and  ])uriileiit  inliannnations  of  the  colon  that 
are  classed  witli  epidemic  di/scnlcr//.  Besides  this  foiin  of  hdcilhaii  dysen- 
tery there  occur  affections  classed  as  dysentery  that  clinically  and  ana- 
tomically are  very  similar  to  it,  but  are  due  to  other  i)arasites,  (ihkiIhv  in 
particular,  or  to  chemically  active  substances  (sid)limate,  septic  poisons), 
or  are  induced  by  fipcal  retention. 

The  dysentery  bacillus  is  a  plump,  short  rod,  with  rounded  ends,  ofieii 
somewhat  tapering  off.  They  have  no  tiagella  and  are  non-mot  lie.  Tliey 
are  easily  stained  by  aniline  dyes  (methyleue-blue,  carbol  fuchsin)  and 
often  show  polar  staining.  They  are  decolorized  by  (i rani's.  On  the 
ordinary  nutrient  media  the  bacillns  giows  best  at  a  temiteiat  ure  of  :\~'^ 
C,    either  under  aerobic  or  anaerobic  conditions. 

That  inflammations  of  the  intestine  similar  to  dy.sentery  may  l)e  jjroduced  by 
baeilH  was  recognized  by  me  as  early  as  18S1  and  1882.  In  the  Insane  A.sylum  at 
Rheinau  during  an  epidemic  I  found  constantly  the  same  bacillus  in  tiie  wall  of  tlie 
thickened  colon.  Cultures  were  not  made,  but  it  is  probable  that  it  was  identical 
with  the  bacillus  cultivated  and  thoroughly  studied  l)y  Shiii(t  and  Knisc. 

According  to  the  American  investigators,  bacillary  dysentery  is  due  to  a  numl)er 
of  types  ot  bacilli,  differing  in  their  fermentative  action,  l)acteri()lytic  and  agglutina- 
tion tests.  In  the  treatment  of  the  disea.se  ,S7(/(/«  reconunends  a  polyvalent  serum 
active  against  all  types. 

Literature. 

(Bacillus  Dyfientcrid'. ) 

Flexner:    Phil.  Med.  Jour.,  1900;   Univ.  of  Penn.  Med.  Bull.,  1901. 

Kruse:   Ruhr  und  Ruhrbacillen.     Deutsch.  med.  Woch.,  1901. 

Kruse  and  Pasquale:  Dysenteric.    Z.  f.  Hyg.,  16  Bd.;  Zeit.  f.  iirztl.  Fortbild.,  i..  19()|. 

Lentz:    Dy.senterie.     Handb.  d.  path.  Mikroorg.,  ii.,  1903  (Lit.). 

Shiga:    Erreger  der  Dysenteric.   C.  f.  B.,  xxiii.,  xxiv.,   1898;    D.  med.\\<.ch..  I'.Kii; 

Z.  f.  Hyg.,  21  Bd.,  1902;  D.  med.  Woch.,  1903. 
"Weichselbaum:   Dysenteric.     Verb.  d.  Deutscli.  path.  Ties.,  iv..  I9(lj. 

8  103.  The  Bacillus  pyocyaneus  Mas  lirst  deinon.st  rated  in  the  i»ns  of 
wounds  in  which  it  had  i)rodnced  a  bluish-green  discoloration.  It  is 
widely  distributed  thronghont  the  outer  world,  being  fonnd  i)arl  icnlai  ly 
in  liquid  manure  and  dung-heai»s,  also  in  water,  and  also  occnis  in  the 
intestinal  contents  of  animals  (swine)  and  of  nniii. 

The  BacillmpiioaianeHH  forms  rods  of  varying  size  (().(i-l-<i  ,",).  '1  hey 
possess  a  terminal  flagellum.     It  is  decolorized  by  Gram's.     Spoies  arc 


602  THE    PATHOGENIC    FISSIOX-FLXGI. 

uot  formed.  It  is  easily  cultivated  upon  the  ordiuary  media  and  pro- 
duces ferments  that  liquefy  gehdin,  coagulate  milk,  and  break  up  albu- 
min. It  produces  a  pigment,  the  (in  the  presence  of  air)  Nuish-green 
pyoci/anhi,  \vhich  is  soluble  in  chloroform,  and  a  greenish  ^fluorescing  pig- 
ment soluble  in  water  but  not  in  chloroform  and  which  in  gelatin  cult- 
ures causes  the  greenish  fluorescence  of  the  gelatin.  For  the  majority 
of  experimental  "animals  it  is  pathogenic,  particularly  for  guinea-pigs 
and  goats,  and  causes  first  local  inflammation  at  the  seat  of  inoculation, 
but  later  may  spread  through  the  blood.  In  bouillon  cultures  it  forms 
both  a  true  toxin  and  an  endotoxin. 

For  man  \i possesses  a  limited ivithogeaicitij.  Xursing  infants  and  chil- 
dren who  have  recently  had  their  resistance  lowered  by  other  diseases 
are  especially  susceptible.  Intestinal  inflammations  are  most  frequently 
to  be  referred  to  the  Bacillus  pnocyaneus,  but  it  may  cause  also  inflamma- 
tions of  the  umbilicus,  middle  ear,  localized  inflammations  of  various 
organs  (endocardium),  and  generalized  infections. 

Literature. 

(Bdcl/his  jti/orjidiirii.s.^  J 

Blum:   Pyocyaneusseptikamie  mit  Endocarditis.     C.  f.  B.,  xxv.,  1899.  . 

Charrin:'  Maladie  pvocyanique.  Paris.  1889. 

Ernst:    Bac.  d.  blauen  Eiters.     Z.  f.  Hyg.,  ii.,  1887. 

Gessard:   Rerh.  sur  le  microbe  pyocyanique.     A.  d.  llnst.  Past.,  1890. 

Heimann:  Bac.  pyoc.  bei  kruposer  Entzundung  d.  Gehorgangs.    C.  f.  B.,  xxxiv.,  Ref., 

190:]. 
Jakowsky:   Bac.  d.  blauen  Eiters.     Z.  f.  Hyg.,  xv..  1893. 
Kossel:    Pathogenitiit  d.  Bac.  pyoc.     Z.  f.  Hyg..  16  Bd..  1894. 
Kramhals:    Pyocyaneusiufection.     D.  Z.  f.  Cliir.,  37  Bd.,  1893. 
Lartigau:    Bac.  pyoc.  as  a  Pathological  Factor.     Phil.  Med.  Jour.,  1898. 
Perkins:   Pyocyaneus  Infection.     .lour,  of  Med.  Res..  1901. 
Wasser?nann:  Bac.  pyoc.     Handle,  d.  path.  .Mikroorg..  iii.,  Jena,  1903  (bit.). 

^  1<)4.  The  Bacillus  tetani  ( ;Kitas;it(»)  is  a  flne,  slender  bacillus  (Fig. 
458)  which  is  widely  distiibiit.-d  throughout  the  superficial  layers  of  the 
earth,  and  is  to  be  regarded  as  the  cause  of  tetanus.  According  to  obser- 
Aations  made  by  Xicolaier  in  1885,  it  is  often  possible  to  produce  in  mice, 
guinea-pigs,  and  rabbits,  by  means  of  subcutaneous  inoculation  of  sur- 
face-earth, a  typical  tetanus  with  fatal  termination,  due  to  this  l)acillus. 

It  was  first  demonstrated  by  Eosenbach  in  1886  that  this  same  form 
of  bacillus  is  present  in  the  seat  of  injury  in  cases  of  tetanus  in  man  fol- 
lowing trauma  or  freezing;  and  that  Mhen  inoculated  into  guinea-pigs 
and  mice  it  again  produces  tetanus.  Since  that  time  this  discovery  has 
been  many  times  coiroborated. 

Tiie  tetanus-bacillus  is  anaerobic  and  thrives  very  well  in  an  atmos- 
phere of  hydrogen,  but  not  in  carbonic-acid  gas.  It  grows  on  ordinary 
peptone-agar  that  is  slightly  alkaline,  on  blood-serum,  and  in  nutrient 
gelatin.  The  latter  is  liquefied  with  evolution  of  gas.  Tlie  addition  of 
from  1.5  to  2  per  cent,  grape-sugar  to  agar-agar  accelerates  the  gi-owth; 
;i  tcmperatui-e  of  .3()°-.')8°  ('.  is  most  favorable  for  its  develoi)nient.  It 
forms  long,  thin,  bristle-sha]HMl  rods  which  form  terminal  s])ores  (Fig. 
458)  giving  rise  to  a  spherical  swelling  at  the  end  of  the  rod  (knobbed 
bacilli).  In  cultures  it  may  form  long  ])seudothreads.  The  cultures 
give  off  an  offensive  odor;  gelatin  is  slowly  liquefied.  The  bacilli  stain 
by  Cram's  method.     Tliey  are  motile  except  during  the  time  of  sj)ore- 


BACILLl\S   TJ:TA.\I.  (iO.S 

foniuitioii,  and  jtossi-ss  peiitrielioiis  lla.uclla.  I'liic  cultures  inoculalfd 
iuto  horses,  asses,  jiuinea-pijis,  ]ui<-e,  rats,  and  rabbits  eause  letanus,  but 
in  the  ease  of  rabbits  iar,uer  amounts  must  be  iujceted.  Tiietelaui*-  <-on- 
tractiiresb(',uiuiii  tlie  iiei.uhboihood  of  tin-  jx.int  of  inoeulat  i(»u.  Suppura- 
tion does  not  oeeur  at  tlie  point  <tf  inoculation.  Tlu^  bacilli  cannot  be 
demonstrated  after  the  death  of  liie  animal,  and  arc 
never  J'ound  in  the  tissues  exeepl  at  the  scat  of  in(»cula- 
tion. 

The  s])eciiic  action  of  the  tetanus-bacillus  is  lo  lie  re- 
ferred lo  the  i)roduetion  of  a  true  loxin  {Idaims  toxin) 
■\vhieh  Ihroujih  its  hapto])hore  i;-roup  is  bound  lo  tiic 
cells  of  the  lU'rvous  system,  and  thei'eby  after  a.  ccrlnin 
X)eriod  of  incubation  excites  tetanic  ecmvnlsions.  An 
antitoxin  is  produced  in  the  body  of  man  and  expcii 
mental  animals  and  by  it  animals  ma>'  be  nnuh'  immune 
against  tetanus  (see  ^  oL*). 

The  infection — intoxication — of  man  takes  phice  usually  tliroujih  the 
medium  of  small  wounds;  idiopathic  or  rheumatic  tetanus,  which  does 
not  start  from  d'i'nionstrable  Avonnds,  may  arise  thr<mj;li  infection  from 
the  mouth-cavity  and  the  ivsj  »i  rat  ory  tract  (Carboue,  JVrrero.  Thalmanni. 
A  preexistinji- catarrh  favors  the  infection  (Thalmann).  When  tak»Mi 
into  the  alinuMitary  tract  the  i)oison  becomes  inacti\e  as  the  result  of 
chanucs  ]H'oduced  by  the  di;4<'stive  juices  (see  i^  •_'!>). 

'\'\\v  tetanus=baciilus  is  nof  rdiiiid  i-olalcd  fitlicr  in  tlu;  cjirtli  or  in  inl'ccieii 
Avounds;  and  inoculations,  theret'oic,  consist  of  a  mixture  of  bacteria.  Attempts  to 
isolate  the  bacillus  by  means  of  cultures  were  therefore  unsuccessful  with  the  majority 
of  investigators.  In  the  year  1889  Kitasnto.  in  Koch's  laboratory,  succeeded  in  iso- 
lating the  tetanus-bacillus  by  heating  for  a  half-hovn-  to  one  hour,  on  the  \vater-l)atli. 
at  80°  C.  mixed  cultures  that  had  been  kept  for  several  days  in  the  inculiator.  and 
then  plating  the  cultures  in  an  atmosphere  of  hydrogen.  Tlu-ough  the  heating  the 
bacteria  growing  at  the  same  time  with  the  tetanus-liacilli  were  killed,  while  the  tet- 
anus-bacilli survived.  Tetanus  toxin  {Kitasato)  is  destroyed  l)y  heating  ((1.")°  ('.  and 
over)  for  a  few  minutes  and  by  direct  sunligiit  (fifteen  to  eighteen  hotn-s),  and  loses 
also  its  virulence  in  a  few  weeks  uiuler  the  infiuence  of  diffuse  daylight. 

Literatu  re. 

(lUicilhis    Tclditi.) 

Achard:  Lesions  des  nerfs  dans  le  tetaiios.     Arcii.  de  nied.  exp.,  iv..  1N<I2. 

Babes:   Recii.  sur  le  tetanus.     Ann.  d.  I'lnst.  de  path,  de  Boucarest,  iv.,  1N'.»:;. 

V.  Behring:  Antitoxische  Tetanustherapie.     1).  med.  Woch.,  lOOii. 

Beumer:  Zur  Aetiologie  des  Trismus  sive  Tetanus  neonatorum.  Zeitscii.  f.  Ilvir..  iii., 
1SS7. 

Blumenthal:  Tetanusgift.     Zeitschr.  f.  klin.  Med.,  .VI  Bd..  1S1>7. 

Brieger  u.  Boer:   Toxine  d.  Diphtheric  u.  d.  Tetanus.     Deut.  med.  Woch..  isix;. 

Cai-bone  e  Perrero:   Aetiol.  d.  rheumat.  Tetanus.     ("1)1.  f.  liakt.,  xviii.,  lS!)(i. 

Danysz:    'lOxine  tetanique  et  subst.  nerveux.     Ann.  de  I'lnst.  Pasteur.  ISiMl. 

Engelmann:    Serumtherapie  des  Tetanus,      ^b■mch.  med.  Woch.,  ISiw  (bit.). 

Fermi  u.  Pernossi:    Feb.  das  Tetanusgift.     Zeitschr.  f.  Uyg..  xvi..  18!M. 

Kitasato:  Der  Tetanuserreger.  Verb.  d.  XVI  lb  Congr.  d.  Deut.  Ces.  f.  Cliir..  ISS'.t; 
Deut.  med.  Woch.,  1889:  Tetanusbacillus.  Zeitschr.  f.  Ilyg.,  vii..  I8S9;  'i'etaiius- 
gift.     lb.,  x.,  1891. 

Kitt:   I\'ber  Tetanusimpfungen  bei  Hausthieren.     ('1)1.  f.  liakt.,  vii.,  1890. 

Kohler:    Stand  d.  Senuntherapie  d.  Tetanus.     .Miincli.  med.  Woch.,  189S. 

V.  Lingelsheim:   Tetanus.     Ihmdl).  d.  ]i.  .\bkroorg.  ii.,  .Jena,  19():{  (I,it.). 

Marie:    La  toxine  tetanique.     Ann.  de  I'lnst.  Pasteur,  1897. 

Moschcowitz:  Tetanus,  a  Studv,  etc.  (Lit.).  Studies  from  Dept.of  Palh.of  Colum- 
bia University,  1899-1901. 


604  THE    PATHOGENIC    FISSION-FUNGI. 

Oppenheimer-.'Toxine  und  Antitoxine,  Jena,  1904,  S.  92. 

Rosenbach:   Zur  Aetiol.  d.  Wimdstarrkrampfs.     Langenbeck's  Arch.,  xxxiv.,  1886. 

Roux  ct  Vaillard:    Contr.  a  I'et.  du  tetanos.     Ann.  de  I'lnst.  Pasteur.  1893. 

Thalmann:   Aetiologie  d.  Tetanus.     Zeitschr.  f.  Hyg.,  33  Bd.,  1900  (Lit.). 

Tizzoni:    Sieroterapia  nel  Tetano.     Mem.  della  R.  Ace.  dell'  1st.  di  Bologna,  1900, 

1901. 
Tizzoni  u.  Cattani:    Tetanusgift.     Cbl.  f.  Bakt.,  viii.,  1890;  Arch.  f.  exper.  Pathol., 

27  Bd.,  1890;    Widerstandsfahigkeit  der  Tetanusbacillen.     Arch.  f.  exper.  Path., 

28  Bd.,  1890;  I'cber  die  Arts  einem  Thiere  die  Immunitat  gegen  Tetanus  zu 
iibcrtragen.  Cbl.  f.  Bakt.,  ix.;  Eigenschaften  des  Tetanus-Antitoxins.  lb.,  ix., 
X..  1891. 

Tizzoni,  Cattani  u.  Baquis:    Bakteriol.  Unters.  iib.  d.  Tetanus.     Beitr.  v.  Ziegler, 

vii..  1890. 
Vaillard:    Immunite  contre  le  tetanos.     Ann.  de  I'lnst.  Pasteur,  v.,  1891. 
Wellner;    Tetanu.s.     Ergebn.  d.  allg.  Path.,  iii.,  1897. 
Wiedenmann :  Beitrag  zur  Aetiologie  des  Wundstarrkrampfs.     Zeit.schr.  f.  Hyg.,  v., 

1889. 

§  105.  The  Bacillus  oedematis  maligni  ( Vibrion  .sep^ig-we  of  Pasteur)  is 
an  anaerobic  bacillus  first  carefully  studied  by  E.  Koch.  It  is  present  in 
various  putrefying  substances,  and  its  spores  ai-e  almost  never  absent 
from  earth  fertilized  by  decomi^osing  fluids  or  liquid  manure.  The  bacilli 
are  3-3.5  /^long,  and  1-1.1  /^.  broad;  they  often  form  long  pseudothreads. 
They  resemble  the  anthrax-bacilli,  though  somewhat  more  slender,  are 
rounded  at  the  ends,  and  not  sharply  cut  across.  In  spore-formation  a 
swelling  of  the  rod  takes  place,  as  in  the  case  of  the  Bacillus  hutyricus, 
so  that  si)iudle-  and  tadpole-shaped  forms  arise. 

The  bacillus  is  motile,  and  possesses  flagella  on  the  ends  as  well  as 
on  the  sides.     It  is  not  stained  by  Gram's  method. 

It  grows  in  mitrient  gelatin  as  well  as  in  agar  and  coagulated  blood- 
serum,  but  mnst  be  introduced  deeply  into  tlie  medium  and  protected 
from  the  air.  Xutrient  gelatin  to  which  one  to  two  per  cent,  of  grape- 
sugar  has  been  added  is  an  esi^ecially  favorable  medium  (Fliigge). 
Nutrient  gelatin  and  blood-serum  are  liquefied,  the  latter  with  evolution 
of  gas. 

The  bacillus  can  be  easily  obtained  by  sewing  up  garden- earth  under 
the  skin  of  a  guinea-pig,  care  being  taken  to  j)  re  vent  the  access  of  air  to 
the  point  of  inoculation.  The  ensuing  multiplication  of  the  bacteria  ex- 
cites a  progressive  cedematous  swelling  of  the  subcutaneous  tissue.  At 
a  later  stage  the  bacilli  spread  over  the  serous  membranes,  and  involve 
the  spleen  and  other  organs. 

Mice,  guinea-pigs,  horses,  donkeys,  sheep,  swine,  cattle,  and  pigeons 
are  susceptible  to  the  bacilli;  rabbits  and  fowls  are  less  susceptible, 
while  rats,  dogs,  and  cats  are  still  less  so. 

According  to  ol)servations  by  Brieger,  Ehrlich,  Chauveau,  Arloing, 
andotliers,  the  bacilli  of  malignant  oedema  maj^  also  occasionally  develop 
in  the  human  body,  particularly  when  the  tissues  are  poorly  nourished 
and  the  bacilli  tlnongh  any  accident — i^uncture  of  a  hypodermic  syringe 
— get  into  the  deeper  tissues.  They  excite  gangrenous  processes  associated 
with  luenioirliagic  (edema  and  gas-pi'oduction. 

As  the  Bacillus  phlegmones  emphysematosse  E.  Fraenkel  in  1892 
described  an  anaerobic  bacillus  staining  with  Gi-am's  Avhich  in  many 
cases  is  to  be  regarded  as  the  cause  of  phlegmonous  inflammation  asso- 
ciated with  gas-formation.  According  to  Fraenkel  the  bacillus  is  non- 
motile  and  only  exceptionally  forms  spores.  In  cultures  it  forms  gas. 
It  occurs  in  the  external  world  (by  Fraenkel  it  Avas  demonstrated  upon 
a  splinter  of  wood  with  which  a  man  dying  of  gas-X)hlegmon  had  been 


BACILLIS    PTILEGMO        S    KM  I'll  YSKM  APOSK.  (lOf) 

Avouiulod);  and  ^vllon  iujoetod  siiboutapoously  iiilo  ^iiiiiea-pi'is  or  spur 

rows  produces  a  pi'o.uressiveganjiieiioiis  process  with  disiiiteoiat  i >!'  tlir 

siibcutaneons  tissues  and  musele,  as  well  as  free  eolleetions  of  lluid  and 
gas.  iDtraveiior.s  injection  into  laWhits  and  guinea-pigs  is  followed  hv 
the  formation  of  gas  in  the  internal  oigans. 

Gas-phlegmon  in  man  occurs  most  Vre<|nently  after  severe  injuiies, 
for  example,  com])ound  and  complicated  fractures,  but  nniy  also  proceed 
from  smalMvonnels.  The  bacillus  is  found  at  times  in  companv  with 
other  bacteria,  pus-cocci,  colon-bacilli;  at.  other  times  alone  and  may  b«i 
present  in  foci  in  great  nnnd>ers.  In  i)nre  infections  there  occurs  a  "pro- 
duction of  gas  associated  with  liquefaction  of  the  tissue,  particularly  of 
the  muscles  and  of  the  reticular  coinieclive  tissue. 

It  i:^  probable  that  this  bacillus  is  identical  with  one  desciibed  by 
Ernst,  ^yelch,  and  Xnttall  (by  the  latter  as  JiariUus  arrof/nics  nip.su- 
latus)  as  the  canse  of  "foamy  liver"  Q'Schaumh'her^')  (Ei-nst)— that  is, 
with  a  bacillus  which  is  regarded  as  the  cause  of  gas-formation  in  the 
human  liver  (Ernst).  The  condition  of  "foamy  organs  "  (Schainiiorf/dnr) 
probably  arises  (Eraenkel)  from  the  fact  that"  the  bacillus  in  (jnestiou 
gains  an  entrance  before  death  into  the  tissues,  into  the  liver  in  i)aiticu- 
lar.  Fraenkel  has  obtained  his  gas-bacillus  in  pure  cultures  fj-om  foamy 
organs. 

Besides  Fraenkel 's  gas-bacillus  other  bacteria  can  cause  changes  coi'- 
responding  to  those  of  gas-phlegmon  and  foamy  organs,  especially  as  the 
result  of  a  localization  in  an  already  infected  inflamed  tissue  (lactic-acid- 
bacilli,  proteus  vulgaris,  and  colon-bacilli). 

Literature. 

(Bacilln-s  (Edcmatis  2[aJigni.     Bacillus  FhJcgmours  J-hnphij-sonaiosn.) 

Bachmann:    Bacillus  des  malignen  Oedems.     Cbl.  f.  Bakt.,  Orifr.,  xxxvii.,  1904. 
Brieger  u.  Ehrlich:    Malignes  Oedem  bei  Typiius  abdom.     Berl.  klin.  Woch.,  18S2. 
Cornevin:   Gangrene  foudroyante  et  son  inoculation  preventive.     Rev.  de  med.,  viii., 

ISSS. 
Davids:   Malignes  Oedem.     Ergebn.  d.  a.  P.  vi.,  1901  (Lit.). 
Dansauer:   Gasgangian  (Bact.  coli).     Miinch.  med.  Wocli..  19();i. 
Ernst:  Gasbildende  Anaeroben  u.  ihre  Bez.  z.  Schaumleber.     ^'ircll.  Arch.,  I'A'^  Bd., 

]  n9:^. 
Frankel:     Ueber  die   Gasphlegmone,    Hamburg.  1893.     Gasphlegnione  \nid  Schauni- 

organe.      Z.  f.  Hyg.,  40  Bd.,   1902;    Gasphlegnione,  Ga.scvsten,  Scliaumorgane. 

Ergebn.  d.  allg.  Path.,  viii.,  1,  1904  (Lit.). 
Ghon  u.  Sachs:  Aetiologie  des  Gasbrantles.  Cbl.  f.  Bakt.,  Orig.,  xxxiv..  1903.  u.  xxxv.. 

1904. 
Harris,  Welch:  Morbid  Conditions  caused  bv  Bacillus  Aerogencs  Capsulatus.     Bull. 

of  .lolms  Hopkins  Ho.sp.,  1900. 
Hesse,  W.  u.  R. :    Ziiclitung  der  Oedembacillen.     Dcut.  nicd.  WOcli..  iss.'). 
Hibler:   Durch  anaerobe  Spaltpilze  bedingte  Infect ionsersciiciuiuigcii.     ("1)1.  f.  Bnkt., 

XXV..  1S99. 
Hitschmann  u.  Lindenthal:     Schaumorg.    u.    Sclileimhaulcinpliyscin.      K.  .Vkad., 

ex.,  Wien.  1901. 
Howard:   A  Contribution  to  the  Knowledge  of  Bacillus  Aerogenes Capsulatus.     Wch-li 

Festschrift,  1900:    The  Origin  of  Gas  and  Gas  Cysts  in  the  Central  Xerv()<is  Sys- 
tem.    Jour,  of  Med.  Res.,  1901. 
Jensen:    Malignes  Oedem.     Handb.  d.  jiath.  Mikroorg.,  ii.,  Jena.  19().S  (Lit.  . 
Kamen:  Aetiologie  d.  Gasphlegmone.     Cbl.  f.  B..  Orig.,  xxxv.,  1904. 
Koch,  R,:  Zur  Aetiologie  d.  Milzbrandes.    .Mittlieil.  a.  d.  K.  Ciesundlieitsamte.  i..  IsM . 
Norris:   Infection  with  Bacillus  Aerogenes  Capsulatus.     Amer.  Jour,  of  .Med.  Sciences, 

1 S99. 
Pasteur:  Vibrion  septique.     Bull,  ilc  I'Arad.  rjc  lur.l..  1S77,  ISSl. 
Ronoa:  Nosokomialgangran.     A,  f.  Derm.,  71  J>d.,  1904. 


606 


tup:  pathogenic  itssiox-fungi. 


Sandler:    Oasphleginonc  iind  Schaumorgane.     Cbl.  f.  a.  Path.,  : 
Stolz:  Gasplilrmnone.     Beitr.  v.  Bruns,  33  Bd.,  1902  (Lit.). 
Welch  and  Nuttall:   Johns  Hopkins  Hospital  Bull.,  1892. 
Westenhoeffer:   Schaumorgane  und  Gangrene  foudroyante.     ^ 


las  Bd..  1902. 


ill 


j^  lG(i.  'llic  Bacillus  pneumoniae  (FriecUaiuler)  isaplinii]),  iion-inotile 
bacillus  Avithout  fiaj;olla,  about  0.5-1.25  /j.  broad  and  0.6-().(»  //.  ]ouix.  It 
forms  no  spoivs  (Fig.  459).  It  belongs  to  the  group  known  as  capsuiated 
bacilli  characterized  bj^  the  formation  of  a  well-defined  mucous  capsule. 
It  is  easily  stained  with  aniline  dyes,  but  is  decolorized  by  Grajifs.  It 
grows  easily  on  the  usual  nutrient  media,  under  both 
aerobic  and  anaerobic  conditions,  and  does  not  liquefy  .  ,.--n 

gelatin.  Stab  cultures  iu  nutrient  gelatin  show  the 
form  of  the  so-called  nail-culture  (Fig.  4()0),  in  that 
the  bacteria  growing  over  the  stab-canal  form  a  white 
mass  of  bacilli  similar  to  a  nail-head. 

White  mice  and  guinea-pigs  are  especially  suscep- 
tible to  the  bacillus.  The  first  named  die  svithin  six- 
teen to  forty-eight  hours  after  subcutaneous  inocu- 
lation. The  point  of  inoculation  and  the  regional 
lymph -glands  are  inflamed  and  contain  encapsulated 
bacilli,  and  the  latter  are  found  also  in  the  blood. 
Rabbits  are  almost  immune  to  inocidation. 

Friedliinder   and   Froljenius,    who  first   described 

the  bacillus  (1 882),  believed  that 

it  was  the  most  frequent  cause 

of  croupous  pneumonia,   a  view 

that  nuiy  be   explained  by  its 

confusion  with  the,  at  that  time 

unknown,  BiploeoccuHpneumoniw. 

It  is  now  I'ccognized  that  it  is  but 

relatively   rarely    the  cause    of 

this  disease  (according  to  Weich- 

selbaum,  in  about  six  per  cent  of 

cases,  according  to  Honl,  in  eight 

to  ten  per  cent);  but  it  may 
cause  focal  pneumonia,  pleuritis,  i^ericarditis,  pharyn- 
gitis, rhinitis,  otitis  media,  and  nuMiingitis.  In  severe 
infections  it  can  also  i)ass  into  the  l)lood  and  set  up 
metastases.  In  llie  inflammatoiy  exudates  the  ba- 
cilli are  found  in  the  form  of  lods  and  short  oval  cells 
surrounded  bv  cajtsules,  often  forming  chains  (Fig. 
459). 

Capsulc-lniciUi  similai-  to  the  i)neumonia-bacillus-are 
often  found  in  the  chi-onic  inflammation  of  the  nasal 
luucosa  known  as  oza-ia,  whicli  is  characterized  by 
a  foul-smelling  secicf  ion  and  the  formation  of  scabs; 
and  they  ha\'e  been  (lemoiislralcd  also  in  rliiHosclcroma 
(sec  below),  and  it  has  been  assumed  that  tliey  stand 
iu  causal  relalion  to  these  diseases,  l)ut  this  remains  to  be  (h'leniiincd. 


Fk;.  459.— Bacillus  pucu- 
nioniie  (Friedlan(Jcr).  n. 
Oval  cells  and  rows  of  cells 
with  gelatinous  capsule;  7>, 
rod  with  selatinous  capsule. 

X  S<KI. 


H(,.  4()(\— Nail  slidpi'l 
stab-c  ul  ture  of  tin 
Friedl.inderpneiiiiioni  i- 
\)a(  illiis  111  L'el.itni 


According  to  Frirkf  \\\v  Ijacteriuni  of  FriedUhuhr  is  llic  cliicf  icp 
group  of  bucU'iia  Avliicli  arc  classed  together  mider  the  name  JinciHns 
Intim.  and  represent  varieties  of  a  single  species.     The  tission-funuus 


I 


HACILU  S    OF     IN  in    K.NZA.  (i()7 

n/a'ua-hiU'illus  is  id.Milical  with  llu-  piiciimoiua-hacillus,  i:iolml)lv  also  tlio  Inu-illiis  ficm 
ll.o  iiul.<-ta'(>cs  <.t  iimslui.us  ,irs,ril„.,l  as  tl,,-  lh,rt,n>n„  hu-tis  ,i^ro,in„x  (Kxrlxrirh).  It 
ispossil.lc  that  :.  -.rater  etiological  siiiiiilicaii.r  mav  U-  aDadicd  to  it  in  so  far  as  the 
origin  ot  iimiiy  (iiarrlKvas  is  coiiccriicd. 

Literature. 

(  liiiciHiis   /'iirjiiiKtiiid .   I 

Abel:    Die  Kapselbaeilleii.      Handli.  d.  path.  Mikroorsr.  iii..  .leiia.  19(M  (Lit.). 
Emmerich:   rneumoiiiekokkeii  in  der  Zwiseheiideckfiilhini;-.      I'orf^chr    d     Med     ii 

1SS4.  

Frankel:     Piieuiuoniekokken.     Zoitschr.   I',   klin.    Med      \      \i  •     Dent     nie<|     \\ni-\i 

iNSt).  '  ... 

Fricke:  Ueb.  d.  sog.  Bacillus  mucosus  capsulntus.  Zeit.  f.  livg..  wiii.,  In'.kI  d.ii.). 
Friedlander:  Pneumoniekokken.     Virch.  Arch.,  S7  Hd      ISS''-    Fortsclir     d     Med 

i..  iss:i  '  .     .         ., 

Grimbert:    Pneumobacille  de  Friedlander.     Ann.  de  I'lnst.  Pasteur.  l.S9(». 

Sachs:   Durch  Pneumoniebacillen  verursachto   Erkrankungen    (Prostatitis,   I'.ndoeai-- 

ditis.  Meningitis,  Nephritis).     Z.  f.  Heilk.,  xxiii.,  1<)()2. 
V.  Stuhlern:    Bedeutung  des  Bac.  pneumonia?.     ('.  f.  Bakt.  Orig..  xxxvi.,  IDOL 
Weichselbaum:    L.  c.,  §  153;    Von  einer  Otitis  media  suppiirativa  ausgi  iien.ie.  dunli 

den  Bacillus  pneumonitr  bedingte  AUsremeininfection.      Monatsschr.  f.  ( )!ireiiheilk 

1S8S. 
Wilde:    I'eber  d.  Bacillus  Friedlander.     Cbl.  f.  Bakt.,  xx.,  1890. 

§167.  As  the  influenza=bacillus  ( Fi.ii-.  401)  iIhmv  was  (h'.sciilM-d  I»y 
R.  Pfeiffer,  in  tlie  year  1S92,  a,  bacilln.s  who.sc  occunviicc  in  iiilliiciiza 
has  been  many  limes  eontirmed;  it  is  n<,\v  re<iar(UHl  as  the  cause  of  iiiliii- 
enza.  In  individuals  suti'ering'  from  intlueu/.a  it  is  found  in  llw  catai  ili- 
ally  aftected  respiratory  passages,  oc'^'asionally  also  in  llic  lungs;  :nid  tlu' 
small  bronchi  may  contain  enormous  niunhers  of  the  bacilli  in  i)urc  cul- 
ture. It  is  assumed  that  their  multii)lication  in  the  i'esi)irat(uy  tiact 
gives  rise  to  the  iutiammation,  and  tiuit  the  l)acilli  ])roduce  poisons, 
which,  when  absoibed,  cause  the  symjjtoms  characteristic  of  intliu'uza. 
The  bacilli  nuiy  also  pass  into  the  i)lood  and  become  spread  thiouglioui 
the  body.  The  inflammatory  changes  of  iutei'ual  organs  occuriing  duiing 
influenza  are  to  be  referred  in  part  to  the  influeu/a-bacillus,  in  i)art  to 
llie  poisons  ])roduced  by  them,  and  in  ])art  to  secoiulary  infections. 

The  infltuMiza-bacilli  are  very  small,  thin  rods  with  rounch-d  omls 
I'ig.  4(jl;,  which  lie  separate  or  joined  together  in  two.s.  They  slain 
witli  tlie  ordinary  aniline  dyes,  but  not  by  (iram's  method.  They  ma\' 
he  cultivated  at  the  body-teuiperature  upon  blood-agar  or  upon  ag:ir  that 
lias  been  smeared  with  human  or  pigeon  blood 
or  to  Avhich  milk  has  been  a<Ided.  Tliey  form 
ii|ton  this  medium  small,  drop-like  colonics  as  '^ .^,t l^-r 
clear  as  water.  According  to  (Jhon  and  \' 
i'rciss,  the  nutrient  medium  must  contain  a! 
huniiii.  Spore-formal  ion  has  not  been  obsi-rved 
in  apes  a  catarrhal  inflammation  of  the  respiia 
toiy  tract  may  be  produced  by  intratra(;heal  in 
Jections  of  i)ure  cultures.    lval>l»its  may  be  ]»<>i  '-r-^- 

suiied    througii    the    iucoi-poiation     into     their        vui.    i.;i.     iniiurii/u.i.miiii 
bodies  ot    cultures;  and   are  allecte<|    m  coiise       ,„„,  (fueiKim.       i.ikhi. 
queuceby  a  paralytic  weakening  of  the  musides 

and  dyspnoea.  According  to  Cantaiii,  the  poison  piodiiccd  l.\  iIm-  l>!i<illi 
exerts  its  effects  particularly  u]»oii  the  eeiitial  nerxoiis  s\siom. 


ki 


608  THE    PATHOGENIC    FISSIOX-FUNGI. 

According  to  investigations  by  Czaplewski  and  Hensel  ("  Bakteriolog.  Untersuch. 
iiber  Keuchhusten."  Ce«/r6/.  /.  Bah.,  xxii.,  1897)  and  Koplik  ("Die  Bakteriologie  des 
Keucliluistens,"  Centralbl.  f.  Bakt.,  xxii.,  1897),  there  is  found  in  the  respiratory  tract 
in  whooping-cough  a  small,  non-motile  bacillus  similar  to  the  influenza-bacillus, 
which  is  thouglit  to  be  tlie  cause  of  whooping-cough.  Luzzatto  ("  Zur  Aetiol.  des 
Keuchhustens,"'  Centralbl.  f.  Bakt.,  xxvii.,  1900)  found  in  cases  of  whooping-cough 
two  bacilli,  but  was  unable  to  determine  with  certainty  their  pathogenic  significance. 
Jochynann  and  Krau.se  (''Aetiol.  des  Keuchhustens,"  Zeit.  f.  Nyg.,  36  Bd.,  1901;  Bd. 
44,  1903)  found  in  whooping-cough  a  bacillus  resembling  the  influenza-baciUus  {Bacil- 
lus pertussis,  Eppendorf);  tliis  could  be  cultivated  upon  media  containing  hiemo- 
globin;  they  regard  it  as  the  cause  of  whooping-cougli.  Their  bacillus  is  not  identical 
with  the  one  described  by  Czaplewski  and  Hensel,  and  later  also  bv  Reyher  {Jahrb.  f. 
Kinderheilk..  58  Bd..  1903). 

Literature. 

(BaellJns  of  Influenza.) 

Bautnler:  Die  Influenzaepidemie,  1893-94.  in  Freiburg  i.  Br.    Miinch.  med.  Woch., 

1894. 
Beck:   Influenza.     Ergebn.  d.  allg.Path.,  v.,  1900  (Lit.),  u.  Handb.  d.  path.  Mikroorg., 

iii.,  1903  (Lit.). 
Canon:  Mikroorganismen  im  Blute    von   Influenzakrankcn.     Mrch.  Arch.,   131   Bd., 

1893. 
Cantani:  Wirkung  d.  Influenzabacillen  a.   d.  Centralnervensyst.     Zeitsch.    f.    Hyg., 

xxiii..  1890  (Lit.). 
Ghon  u.Preiss:  Biol.  d.  Influenzabacillen.     C.f.  Bakt.,  Orig.  xxxv.,  1904. 
Grasburger:    Zur  Bakteriologie  d.  Influenza.     Zeitsch.  f.  Hyg..  xxv.,  1897. 
Huber:    Ueber  den  Influenzabacillus.     Zeitschr.  f.  Hyg.,  xv.,  1893. 
Kitasato:  Ueber  den  Influenzabacillus.     Deut.  med.  Woch.,  1892. 
Kruse:    Aetiologie  der  Influenza.     Deut.  med.  Woch.,  1894. 
Kuskow:  Pathol.  Anatomic  d.  Grippe.     Virch.  Arch.,  139  Bd.,  1895  (Lit.). 
Luerssen:    Zur  Biologic  d.  Influenza.     C.  f.  B.,  Orig.,  xxxv.,  1904. 
Nauwerck:    Influenza  u.  Encephalitis.     Deut.  med.  Woch.,  1895. 
Ophiils:  Infection  of  the  Rectum  with  Secondary  Infection  of  the  Liver,   Caused  by 

the  BaciUus  Influenzge  Simihs.     Amer.  Jour,  of  Med.  Sc,  1901. 
Pfeiffer,  A.:    Die  Aetiologie  der  Influenza.     Zeitschr.  f.  Hyg.,  xiii.,  1893. 
Pfiih.1  u.  Walter:    Influenzabacillen  im  Centralnervensystem.     Deut.  med.    Woch., 

1896. 
"Weichselbaum:   Aetiologie  u.  path.  Anat.  d.  Influenza.     Wien.  klin.  Woch.,  1892. 

§  168.  The  Bacillus  diphtheriae  (Fig.  462)  was  first  thoroaghly 
studied  by  Loffler ;  it  is  found  in  the  croupous  membrane  occurring  iu 
diphtheria,  and  is  regarded  as  the  cause  of  this  disease.  In  the  internal 
organs,  as  the  spleen  and  lymph-glands,  it  is  either  entirely  absent  or 
present  iu  such  slight  numbers  that  it  can  be  demonstrated  only  by 
methods  of  cultivation. 

The  bacilli  are  1.5-3  //  long,  and  are  often  somewhat  swollen  at  the 
ends.  In  cultures  they  form  rods  of  varying  length  (Fig.  462),  the  ends 
of  which  are  often  clubbed  or  pointed.  AVhen  stained  the  bacilli  appear 
si)otted  or  granular.  They  stain  best  in  a  staining-solution  composed  of 
•SO  c.c.  of  concentrated  alcoholic  methylene-blue  solution  in  100  c.c,  of 
0.0001  per  cent,  potassium  hydroxide  solution,  after  which  the  sections 
aie  ti-eated  for  a  few  seconds  in  a  0.5-per-cent.  solution  of  acetic  acid 
and  then  with  alcohol.  In  stained  preparations  the  bacilli  often  appear 
.'segmented.  They  al.so  stain  by  Giam's  method,  provided  the  treatment 
with  Lugol's  solution  and  alcohol  is  of  brief  duration. 

Diphtheria-bacilli  grow  best  in  the  presence  of  air  (Loffler)  on  a  niix- 
tureof  three  parts  of  calf's  or  sheeji's  serum,  and  one  part  of  neutralized 
veal-bouillon,  to  which  one  per  cent,  of  peptone,  one  per  cent,  of  grape- 


-^^'•> 

V            ^ 

V 

'':, 

/» 

.*« 

^ 

CJf 

FIG.     4li2.- 

Diphtheria-ba- 

cilli  from    a 

piire 

ciilturf. 

^^reak-I)^'pa^ 

ilioii 

(iiii'thy- 

lene-l.liH').    • 

I.IKIO. 

HACILLI  S    DIPIl  rilKKI.K.  «'•()'.) 

snjjar,  and  O.-T  per  cent,  of  coiniiion  salt  arc  added;  or  \ii)<>ii  l»l»M»d-seiMiin 

aud  a^ar-agar  with  an  aildilion  of  ten  per  cenl.  glveeriii  or  of  siij^ar-eon- 

tainin^-     honillon     (  KolisUo,     Pallaul".     Kilasalo). 

«\  gj       Tliey  I'orni  jirayisli-Nvliite  colonies.      For  llieir  de- 

^^*  velopnient  tliey  need  :i  teniix'ratnre  al)o\eLM)    ( '.  ; 

""  they  jrrow  best  at  33°-37°  C.     They  arc   icsist:iiit 

to  drying,-;   but  may  be   quickly    killed    by    ist 

heat.     Spore-iorniation  has  not  been  obser\c(l. 

(Iiihicd-pif/s  iiiocuUdcd  .siihcutaiKouslii  with  cul- 
tures of  di])htheria-l)acilli  die  in  two  1o  thi'cc  days 
(  Liililer,  Koux,  Yersin  ) ;  whitish  <leposits  and  a 
lueniorrhagic  (edema  aie  found  at  the  point  of  the 
inoculation.  The  inoculation-area  contains  bacilli, 
the  internal  organs,  on  the  contrary,  are  free.  The 
hitnulKction  of  cuUurcH  into  Hie  opened  traehea  of 
rabbits,  chickens,  and  ])igeons,  as  well  as  the  inoe- 
nhdion  oj't/ie  eonjnnetira  of  rabbits  and  the  viKjina  of  (/i(ine((-j)i(/.s  is  followed 
by  an  iutlammatiou  with  the  formation  of  a  i>seudomeud»rane.  Sheep, 
horses,  cats,  dogs,  cows,  rabbits,  aud  pigeons  are  suscejttible  to  subcu- 
taneous inoculation.     Hats  aud  Mliite  mice  ai'e  nearly  immun*'. 

Roux,  Yeisin,  LofHer,  Spronck,  aud  otheisobseixcd  the  latei-  a])i)ear- 
auce  of  paralysis  in  pigeons  and  guinea-pigs  survi\ing  the  inoculation. 
Eoux  and  Yersin  assertthat  the  intravenous  injection  of  filtered  bouillon- 
cnltures  free  from  bacteria  will  cause  in  guinea-]>igsand  ral>bits  after  two 
to  three  days  a  severe  illness  characterized  l)y  paralysis  and  fatal  termi- 
iiatiou. 

The  virulence  of  the  cultures  varies  greatly.  Diphtheria  bacilli  pro- 
duce iu  the  human  body  and  also  in  cultures  toxins,  which  may  be  pre- 
cii)itated  by  alcohol  aud  obtained  as  a  whitish  i)ow(ler. 

Water-solutions  of  the  poison  injected  subcutaneously  into  animals 
cause  local  tissue-necrosis,  hiemorrhagic  oedema,  and  intlammatiou  ;  wluui 
taken  up  into  the  body-juices  they  give  rise  to  pleural  effusions,  nei)hri- 
tis,  fatty  degeneration  of  the  liver,  and  paralysis. 

Diphtheria  in  man  is  characterized  by  an  intlammatiou  iuvolving  usu- 
ally the  mucous  membraiu-  of  the  phaiyux,  palate,  arch  of  the  i)alate, 
and  upper  resj)iiatoiy  i)assages.  It  ap])ears  as  a  febrile  infe<-tioii.s  dis- 
ease asHoei(ded  iritli  si/)npto)iis  of  intoxication  and  gives  rise  to  local  eronpons 
exudations,  in  part  also  to  diphtheritic  sloughings  (cf.  S  l>i,  Figs.  1!M», 
200).  The  croupous  mend)ranes  constitute  the  most  striking  featuie  of 
the  disease;  they  are  found  in  the  throat  and  nose  usually  in  the  form  of 
circumscribed  fiat  patches,  more  rarely  uniforndy  s])read  ovei-  larger 
areas;  or,  ou  the  other  hand,  they  may  form  a  continuous  layer  lining 
the  larynx  aud  trachea,  or  even  the  bronchi.  Beneath  tlu'  cioupons 
membrane  the  ei)ithelium  is  for  the  greatei'  part  lost  ;  aud  the  connective 
tissue  of  the  mucosa  is  liypenemic,  infiltrated,  and  swollen  (Fig.  1!M>). 
In  severe  cases  the  superlicial  layers  of  the  conuj'ctive tissue  are  ueci-otn- 
in  places,  most  frequently  iu  the  tonsils,  which  are  more  or  h'ss,  often 
markedly,  swollen.  Of  ^ the  deeper  tissues  tlu'  neighboring  cervical 
Ij/mph-f/lands  in  particular  are  swollen,  and  often  show,  when  exanuue«l 
microscopically,  snmll  foci  of  necrosis  an<l  degenei-at ion.  Of  the  inter- 
nal organs  the  kidneys  especially  are  accustonu-d  to  show  changes,  in  the 
foi-m  of  a  more  or  less  severe  fatty  degeneration  of  the  epithelium  and 
of  the  cells  of  the  capillary  walls ;  not  infre(|uently  they  also  present 
swellings  and  focal  areas  of  small-celled  inliltrat  ion.  In  Hh-  spleen 
39 


610  THE    PATHOGENIC    FISSION-FUNGT. 

tlioreiire  fie(|ueii1iy  found  areas  of  degeneration  in  the  white-appearing 
follicles,  in  which  the  cells  are  more  or  less  necrosed,  in  part  disinte- 
grated and  have  lost  their  nuclei.  In  the  blood  many  of  the  leucocytes 
show  fatty  degeneration.  Degenerative  changes  and  areas  of  inflamma- 
tion are  not  infrequently  found  in  the  heart-muscle.  Paralyses  are 
caused  by  degeneration  and  necrosis  (Katz)  of  the  ganglion -cells  of  the 
medulla  oblongata  and  of  the  spinal  cord  and  of  the  corresponding 
nerves. 

The  lungs  are  not  demonstrably  changed  by  the  diphtheria  poison, 
l)ut  bronchopneamonia,  due  to  the  asj)iration  of  irritating  bronchial 
contents  or  to  an  extension  of  the  bronchial  iufiammatiou  to  the  respi- 
ratory parenchyma,  is  of  frequent  occurrence. 

The  local  inflammations  of  the  mucous  membranes  as  well  as  the  symp- 
toms of  intoxication  may  be  caused  by  the  diphtheria  bacilli  and  their  toxins 
alone ;  but  it  must  be  noted  that  streptococci  are  almost  regularly  pres- 
ent in  the  diseased  area,  and  that  a  pure  fitreptococcus  infection  may 
present  the  clinical  and  anatomical  picture  of  a  ^^ diphtheria."  When 
botli  bacteria  are  present  the  injurious  effect  of  one  may  be  supple- 
mented by  that  of  the  other,  and  the  presence  of  streptococci  appears  to 
increase  the  virulence  of  the  bacilli.  In  severe  forms  of  diphtheria 
streptococci  are  usually  present  in  great  numbers ;  yet  every  streptococ- 
cus infection  does  not  warrant  a  bad  prognosis,  since  the  virulence  of  the 
cocci  varies  greatly. 

In  the  course  of  the  infection  with  diphtheria  bacilli  there  arise  in  the 
body  antitoxins,  which  nullify  the  poisonous  action  of  the  toxins,  and  aid 
and  make  possible  recovery  from  the  disease.  The  formation  of  anti- 
toxins follows  the  inoculation  of  animals  with  attenuated  bacilli,  aixl 
upon  this  rests  the  i30ssil)ility  of  obtaining  from  animals  (sheep,  horses), 
that  have  been  repeatedly  inoculated  with  bacilli  of  increasing  virulence, 
a  ."serum  which  contains  an  antitoxin  of  value  for  therapeutic  purposes 
(ef.  §  32). 

Lchmann  and  Neumann  call  the  diphtheria-bacillus  corynehacterium  on  account  of  f 
the  ckib-shaped  appearance  of  the  rods.     Since  the  bacilU  can  also  form  branching  k 
threcula  in  cultures,  they  class  it  with  the  hyphomycetes,  among  which  tlie  tubercle-bacil- 
lus and  the  fungus  of  actinomyces  (oospora)  are  also  classed  by  them  and  others. 

Ehrlich  distinguishes  different  kinds  of  poisons  produced  by  the  diplitheria-bacil- 
lus,  namely,  toxins  and  toxons,  these  again  representing  no  bodies  of  defuiite  unity,  but 
breaking  up  into  several  subdivisions  (prototoxin,  deuterotoxin,  and  tritotoxin)  which 
are  distinguished  by  the  different  degrees  of  avidity  with  which  they  unite  with  the 
antitoxin.  The  toxin  produces  the  typical  picture  of  the  disease,  while  the  toxon 
causes  the  after-symptoms,  marasmus  and  i>are  ;es.  The  toxon  shows  a  less  affinity 
for  the  antitoxin. 

As  a  lethal  dose  of  fiie  <liphtheria  poison  Ehrlich  designates  that  amount  of  the 
poison  which  is  sufficient  to  kill  in  4-.5  days  a  guinea-pig  weighing  '2'A)  gm.  As  a  nor- 
mal poison  von  Behring  designates  a  solution  of  the  poison  which  contains  one  hun- 
dred lethal  doses  per  c.c.  A  simple  healing  serum  or  a  unit  of  the  antitoxin,  that  'is, 
one  immunity  unit  (I.-E.)  is  one,  1  c.c.  of  which  will  neutralize  1  c.c.  of  the  normal 
poison. 

According  to  Lofflcr,  ron.  Hoffmann,  Roux,  Yersin,  Babes,  and  otliers  there  are 
very  frccpicntly  prcM-nt  in  the  mouth  and  throat  bacilli,  which  are  often  designated 
pseudo=diphtheria  bacilli.  These  resemble  the  true  bacilli  of  diphtheria  and  can  be 
di.stinguished  from  them  only  in  cultures.  Since  the  diphtheria-bacilli  can  lose  their  j? 
virulence,  it  is  not  impossible  (Raax,  Yersin)  that  both  bacilU  represent  varieties  ofi 
tiie  same  species.  Lewanduwsky  distinguislies  four  forms  as  belonging  to  the  group; 
of  corynebacteria:  Corynebacterium  commune  {B.  pseudo-diphthericum),  C.  diphthericBy 
C.  conjunctiva  {B.  xerosin),  C.  pyogenes. 


liAcii.M  s   Diriii  II  iiKi.i:.  ''11 

Literature. 

(J>iplll/ir)'i(l  Klltl   I'siiiilo-dijiJilliirid   Ji<i<-i/li.) 

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1S91:  Virch.  Arch.,  119  Bd.,  1890. 
Bag-insky:   Diphtherie  ii.  diphther.  Croup,  Wicn,  1S9S. 
Barbacci:    Alterat.  d.  Milz,  Lymphdriiseu  u.  Leber  l)ci   Diplith.     ('1)1.  f.  mH-:.   l':ith., 

vii.,  189(). 
Barbier:    Dc  tpiclqucs  associat.  niicrobicnncs  dans  la  diplitlicric.     Arch,  dc  nicil.  c\p., 

iii.,  1S91. 
Beck:    Diphtheric.     Handb.  d.  p.  Mikroor^.,  ii..  Jena,  190;i  (Lit.). 
Behring:   Die  Gescliichte  d.  Diphtheric  init  Beriiclcsichtigunfi  d.    Iinnnniitalslclirr, 

Lci]izig,  1893. 
Beruheim:   Mischinfection  bei   Diphtherie.     Zcitschr.   f.    Ilyg.,   xviii.,    1S94;     Patli- 

oijcnese  d.  schweren  Diphtheric,  Wicn,  1898. 
Blasi:   Association  bacter.  dans  la  diphtherie.     Ann.  de  Tlnst.  Past.,  1890. 
Bock:   Bakt.  Unters.  iiber  die  Actiologie  der  Diphtheric.     Zcitschr.  f.  Ilyg.,  viii.,  189(». 
Brieger  u.  Boer:   Toxine  d.  Diphtlicric.     Dcut.  nicd.  Woch.,  189(5. 
Chaillon  ct  Martin:    Et.  ciin.  et  bacter.  .sur  la  (Uph.     Ann.  de  I'lnst.  Pasteur,  1894. 
Colbet:    Pscudodiplithcria  Bacillus.     Journ.  of  Path,  iv.,  1896. 
Councilman,  Mallory  and  Pearce:   A  Study  of  the  Bacteriology  and  Pathology  of 

Two  Hundred  and  Twcnty-tive  Fatal  Cases  of  Diphtlieria.     .lour,  of  Bost.  Soc.  of 

.Med.  Sc,  1900. 
Crocq:  Alter.du  syst.nerveux  dans  les  paraly.s.diphth.     Arcli. dc  ni('d.c\|).,  isit,")  (l.ir.i. 
Denny:    Morphology  of  B.  Diphtherise,  B.  Pseu(io-(nj)hthcria'.  and  B.  Xerosis.     .lom-. 

of  Med.  Res.,  1903. 
V.  Dungern:  Mischinfection  bei  Diphtherie.     Bcitr.  v.  Zicglcr.  xxi.,  1897;    Bindungs- 

v^'rhiiltnisse  von  Diphtheriegift  und  Antiserum.     I),  nied.  Woch.,  1904. 
Ehrlich:   Konstitutiond.  Diphtheriegiftes.    I),  nicd.  Woch.,  1898,  u.  Berl.  kiln.  Wod,.. 

1903. 
Ehrlich.   u.   Wassermann:     Die   Gewinnung   d.  Diphtherieantitoxinc.     Zcitschr.   f. 

Hyg.,  xviii.,  1894. 
Escherich:   Aetiologie  u.  Pathogenese  der  Diphtherie,  Wien,  1894. 
Fliigge:   Verbreitungsweise  der  Diphtherie.     Zeitschr.  f.  Hyg.,  .xvii.,  1894. 
Frosch:    Verbreitung  des  Diphtheriebac.  im  Kcirpcr.     Zeitschr.  f.  Hyg.,  xiii.,  1X9:;. 
Gorham:  Morphological  Varieties  of  Bacillus  Diplitheria».     Jour,  of  ^leil.  Res.,    1901. 
Guinochet:  Contr.  a  I'et.  de  la  toxine  du  bacille  de  la  diphtherie.     Arch,  dc    mcd. 

cxp.,  iv.,  1892. 
Henke:   Exp.  Erzeugung  d.  Diphtherie.     Arb.  a.  d.  path.  Inst,  zu  Tubingen,  ii.,  1890. 
Hilbert:  Mischinfection  bei  Diphtlicric.     Dcut.  Arch.  f.  kUn.  Med.,  o9    Bd.,    1897; 

Steigerung  d.  Giftproduction  an  Diphtheriehacillcn  (lurch  Symbiose  m.  Strepto- 

kokken.     Zeitschr.  f.  Hyg.,  29  Bd.,  1898. 
Hill:   Branching  in  Bacteria  with  Special  Reference  to  Bacillus  l)i])]itlicria'.     Jour,  of 

Med.  Res.,  1902. 
Katz:    Diphtherische  Lahmungen.     Arch.  f.  Kinderheilk.,  1897. 
Klein:    Beitrage  zur  Aetiologie  der  Diphtherie.     Cbl.  f.  liakt.,  vii.,  1890. 
Kober:    Diphtheriebacillen  auf  d.  Mundschleimliaut  gesunder  Mcnschcn.     Zcifscli.  f. 

Hvg.,  31  Bd.,  1899. 
Kossei:    Zur  Kenntniss  d.  Diplitheriegiftcs.     Cbl.  f.  Bakt.,  xix.,  189G. 
Kutscher:    Nachweis  d.  Diphtheriebac.  in  d.  Lunge.     Zeit.schr.  f.  Hyg.,  xviii.,  1894. 
Lewandowsky:   Die  Pseudodiphthericbacillcn.     Cl)l.  f.  Bakt.  Orig.,  xxx\i..  1904. 
Loffler:   luitstchung  der  Diphtheric.      Dcut.  nied.  Woch.,  1890;   Bc.lcutunji  <l<r  .Mikro- 

or^anisnien  fur  die  Kntstehuni:  der  Dijjhtheric.     Mitthcil.  a.  d.  Kais.  G<-sundlieits- 

anitc,  ii.,  Berlin,  1884,  u.  1).  mcd.  Woch.,  1890. 
Madsen:  Zur  Biolcgie  d.  Diphtheriebacillen.     Zcit.schr.  f.  Hyg.,xxvi.,  1897. 
Millard  ct  Regaud:    Myocardite  dipiitherique.     Ann.  dc  I'lnst.  Pasteur,  1897  (Lit.). 
Morgenroth:    Bindung  v.  Diphtherictoxin  u.  Antitoxin.     Z.  f.  Hyg.,  4S  Bd.,   1904. 
MouraviefF:    Infl.  d>-  la  toxine  dijiiith.  sur  le  syst.  ncr\'eux.      Arch,  dc  nicd.  cxi>.,  1897, 
Oertel:   Die  Pathogenese  der  epidem.  Diphtlicric,    Leipzig,    1887;    Das  diphtheriselic 

Gift.     Deut.  med.  Woch.,  1890;   Toxine  und  Antitoxinc,  .Jena.  1904. 
Peters:    Diphtheria  u.  Pseudodiphtheria  Bacilli.     Journ.  of  Piith.,  iv.,  1890. 
Proschaska:    Pseudodiphtheriabacillcn  d.  Rachens.     Zcit.schr.  f.  Hyg.,  xxiv..  1S97. 
Prudden:    Studies  on  the  Etiology  of  Dijihf heria.     Med.  Rcc,  New  York,  1X91. 
Roux  et  Martin:    Serotherapie  dc  la  diplitherie.     Ann.  dc  I'lnst.  Pasteur,  vni.,  lS9t. 
Roux  ct  Yersin:    Diphtherie.     Ann.  de  I'lnst.  Past.,  ii.,  1888;    iv.,  1890. 
Schottelius:  Wachsthum  d.  Diphtheriebac.  in  d.  .Milch.     Cbl.  f.  Bakt.,  xx.,  189G. 
Schlesinger.  Diphtheric  d.  Ccaijnnciiva.     Miincli.  mcd.  Woch..  lOo, 


612  THE    PATHOGENIC    FISSIOX-FUXGI. 

Slawyk  u.  Manicatide:  Variabilitat  d.  Diphtheriebacillen.     Zeit.  f.  Hyg.,  29 Bd.,  1S9S. 
Spronck:    ratliom'iie  Bedeutung  d.  Diplitlieriebacilhis.     Cbl.  f.  allg!!  Path.,  i.,  1890; 

Invasion  des  JJiphtheriebacillus  in  d.  Unterhaut  d.  Menschen.     lb.,  iii.,  1892. 
Welch:    The  Histological  Changes  in  Exp.  Diphtheria.     Bull,  of  the  Johns  Hopk. 

Hosp.,  ii..  1S91. 
Welch,  and  Abbot;   The  Etiology  of  Diphtheria.     Bull,  of  the  Johns  Hopk.  Hosp.,  ii., 

1891.  _  "_  '        ! 

Williams:   Persistence  of  Varieties  of  B.  Diphtheriaj  and  of  Diphtheria-like  Bacilli,  t 

Jour,  of  Med.  Res.,  1902. 

See  also  g  33. 

§169.   The  bacillus  of  bubonic  plague   (Bacillus   pestis)   was  dis-'i 
covered  in  ISD-t  by  Kitasato  and  Yersin,  of  the  Japanese  and  French  com-  |i 
mission,  while  investigating  an  epidemic  which  had  brolcen  ont  in  Hong-  ■ 
Kong.     The  pest-bacilliis  isa  small  rod  with  ronuded  ends  (resembling; 
the  bacillns  of  chicken-cholera).     It  stains  easily  with  aniline  dyes,  es- 
pecially well  with  methylene-blne,  and  in  part  shows  an  e.xqnisite  polar: 
staining  (Fig.  463).     It  is  decolorized  by  Gram's  method.     It  is  fonnd 
in  all  cases  of  plagne,  in  especial  abnndance  in  the  swollen  lym])h-glands, 
bnt  also  in  the  spleen  and  blood.     It  may  be  cnltivated  npon  the  various | 
media,  and  forms  blnish-gray  colonies,  which  contain  rods  of  various i 
lengths.      It  mnltiplies  abundantly  in  bouillon  containing  sugar,   and 
forms  toxins.     Independent  movements  have  not  been  observed.     Spores 
are  not  formed.     The  bacilli  are  easily  killed  by  warming,  but  are  able, 
to  withstand  drying  well. 

The  bubonic 2)Ja(/ue,  which  destroyed  great  numbers  of  the  inhabitants; 
of  Europe,  at  the  close  of  the  seventeenth  and  beginning  of  the  eigh-k, 
teenth  centuries  (''Black  Death"),  has  since  1720  almost  disappeared! 
from  Europe  and  has  shown  itself  only  here  and  there  in  Eastern  Enrope. ' 
In  different  countries  of  Asia  (Yunnan  in  China,  Arabia,  Me.'-oj)otamia  ), ' 
and  in  the  interior  of  Africa  (Koch)  the  disease  seems  to  be  endemic, 
and  spreads  from  time  to  time  in  the  same  mauner  as  cholera. 

]\Ian  is  infected  usually  through  the  skin,  more  rarely  from  the  mu-: 
cons  membrane  of  the  month,  nose,  throat,  and  conjunctiva,  still  more 
rarely  from  the  deeper  x^arts  of  the  respiratory  tract,  although  cases  of' 
primary  pest-bronchitis  and  pest-pneumonia  occur.  Small  wounds  usu- 
ally form  the  avenue  of  entrance  in  the  skin,  but  it  appears  (Albrechf 
and  Ghon)  that  a  violent  rubbing  of  an  area  of  the  skin  with  infected 
fingers  or  clothing  may  be  sufficient  to  bring  about  an  infection. 

The  l)acilli  are  taken  up  by  the  lymj)h- vessels  and  taken  to  the 
regional  Itpnph-filandH,  where  they  cause  a  very  marked  swelling  of  tlie 
infected  ghmd  or  group  of  glands — the  prhnarn  bubo.  Through  the  in- 
fection of  lymph-glands  situated  farther 
along  the  lymi)h-sj'stem  there  arise  jir/- 
mary  buboes  of  the  second  class,  and  by 
metastasis  through  the  blood-stream 
secondarif  buboes  are  formed.  The  plague 
is  thus  characterized  in  the  first  place  by 
an  acute  pohjadcnitis.  Since  the  poisons 
which  ar(!  in  association  with  the  bodies 
of  the  pest-bacilli  exert  a  degenerative 
and  necrotic  effect  upon  the  vessel-walls, 
numerous  liwmorrhages  are  also  caused, 
and  these  are  absent  only  in  rare  cases, 
'^ro  these  changes  there  are  also  added 
cii-cumsciibed  foci  in  the  spleen,  liver, 
kidneys,  Inngs,  skin,  etc.      \Vith  the  exception,  therefore,  of  tho.se  cases 


-  1 

s 

:? 

•• 
z 

0^- 

\* 

:*^.-.  .f:..; 

/' 

*• 

-    V   ^.   S   "^^ 

^* 

*!• 

Fig.  4*«.— Plague  bacilli  (fuchsin).    X  oSO. 

HAciLLis  i'i:s'ris.  r.i;5 

in  Avhk'h  the  iH'sl-infcetioii  s  couliiHul  to  tlw  piimary  bubo,  tli<' di^riist' 
is  to  bo  ro.uarded  ;is  -x  f/cncraJ  iiifrrtiou  (  Albrrclit  ;iii«l  (Ihoii  ),  wliicli  ;iris«'s 
from  the  t:ikiiig-U|)  oi"  bacteria  from  a  i)rimaiy  focus  <»r  inrcclion,  and 
runs  its  course  witli  tlie  clinical  picture  of  a  jiofifadniitis  and  a  s«-\.iv 
heniorrhaf/ic  srj)ti('<riii  i<i. 

The  indi\  idual  foci  are  characterized  l)y  tissne  necroses  of  tho  nature 
of  codf/iihdion-HirroNis  (  Albrecht  and  (Jhon).  as  well  as  l»y  smrf  rxinln- 
tioihs,  i)itf((iiiin«tio)>,  ami  hamorrhagc,  and  are  caused  by  the  i)i'esence  of 
extraordinarily  large  mnnbers  of  bacilli.  The  lympli-j^lands  of  the  i)ri- 
mary  bubo  show  either  wholly  or  for  the  cliief"i)ai't  the  ap]>earance  of 
haeniorrliagic  infarction,  and  are  swollen  and  of  a  medullary  ctnisistencc 
After  the  course  of  a  few  days  they  also  show  yellow  neci-otic  art'as  wliicli 
later  undergo  liquefactiim.  When  the  disease  has  lasted  longer  thari  six- 
days,  the  liquefaction  of  the  Ijmph-glands  may  take  on  the  eiiaracter  of 
a  suppi(r((iion. 

The  tissues  in  the  neighborhood  of  the  lym])h-glaiid  are  :il\\a.\s  more 
or  less  cedematously  swollen,  infiltrated  with  blood;  and  hieniorriiaucs 
are  also  found  in  the  walls  of  the  neighboring  large  veins. 

The  secondary  inflammations  of  the  lymph-glands  and  of  the  lymph - 
adenoid  tissue  of  the  mouth  and  throat  do  not  usually  cause  sucii  a 
marked  degree  of  swelling  as  do  the  i)rimary ;  they  reseml)Ie  the  medul- 
lary swelling  occurring  in  typhoid  fevei-.  The  surrounding  tissues  are 
also  less  changed,  but  if  the  i)rocess  be  i)rol<)nged  the  ]»ictnre  comes  to 
resemble  that  of  the  primaiy  buboes. 

The  spleen  of  plague-patients  is  somewhat  swollen,  daik  led,  finely 
granular,  shagreened  (Albrecht  and  Uhon),  and  often  contains  small 
necrotic  foci,  which  are  caused  by  the  development  of  the  bacilli  in  gieat 
numbers. 

In  the  glandular  organs  and  in  the  skin,  there  occur,  Ix'sides  luemor- 
rhages,  also  necrotic  areas  and  exudatixe  intlanimations,  all  due  to  the 
presence  of  bacilli.  In  the  lungs  there  may  occni-,  in  addition  to  the 
primary  pest-bronchopnenmonia,  secondary  metastatic  focal  inllamma- 
tions  and  aspiration-bronchopneunionias. 

The  majority  of  individuals  infected  with  ])est  die  within  ilie  lirst 
eight  days,  but  otheis  may  live  se\ei-al  weeks  and  then  die  of  maras- 
mus.^ 

"Not  infreqnenUy  srcondarj/  i)tffrfi())in,  ])aiticularly  of  streptococci  and 
diplococci,  are  associated  Avith  the  j)esl-iiitection.  They  arise  chielly  in 
the  tonsils  and  follicular  glands  of  the  tongue  following  the  changes 
caused  by  the  pest-bacilli  (Albrecht  and  (ihon). 

Among  animals,  rats,  mice,  aprs,  and  cats  arc  csjircia/li/  .sK.sripllh/r  In 
pest;  and  in  these,  pai'ticnlarly  in  rats,  si)ontaneous  infections  occur,  so 
that  they  may  aid  in  the  s])read  of  ei)idemics.  Swine  and  dogs  ai-e  less 
susceptible,  birds  still  less  so. 

Th(^  changes  in  infected  animals  agree  in  gen(Mal  \\  itli  those  oltset\e(l 
in  man.  The  infection  may  remain  local  or  become  general.  After  the 
lymphadenitis  and  the  multiple  ha'nn)iihages  there  arise  also  miliary, 
tubercle-like  foci  in  the  si)leen,  li\ei',  and  lung.s.  Tlu' couise  is  usuall.\ 
acute,  rarely  chronic.  In  the  latter  case  tlu^  laiger  necr<»tic  foci  may  be 
encapsulated  by  connective  tissue.  The  animals  aic  easily  inlected  fiom 
the  skin,  as  well  as  from  the  mucous  nMMid)i-anes  of  the  intestinal  and 
respiratory  tracts;  and  such  infection  may  take  ])laee  from  an  uninjured 
mucous  membrane.  The  inoculation  of  one  mouse  confined  in  a  cage 
with  other  mice  may  give  rise  to  a  cage-epidemic  (Schotteliiis  i. 


(114  THE    PATHOGENIC    FISSION-FUNGI. 

Attempts  ioiinmnnize  rtnnnfilK  ami  man  against  pefit  hy  means  of  dead  and  aUcnvafed 
jifxt-baciUi  have  been  many  times  cairicd  nut,  especially  by  Tersin,  llaffkin,  and  Lux- 
liy  :  and  Iiave  been  successful  in  so  far  that  rodents,  horses,  and  apes  have  l)een  ren- 
dered imiiiuiie  against  inoculations  otherwise  fatal.  According  to  the  reports  of  such 
attempts  in  man,' a  smaller  per  cent,  of  inoculated  individuals  acquire  the  disease  than 
(if  those  not  inoculated  ;  Imt  doubt  is  thrown  upon  the  results  of  these  inoculations  by 
other  authors  (Bitter).  Further,  attempts  at  immunization  and  healing  hate  be^n  made 
ill  man.  ii-itli  the  sernni  of  animcds  w/iich  hare  been  rendered  immune,  particularly  of 
liorses  ( Yei:sin,  Lti.stig) ;  and  different  authors  ascribe  to  such  serum  a  favorable  influ- 
ence. 

Sticker  differentiates  the  following  forms  of  pest  according  to  the  first  localization 
of  the  bacilli:  (1)  Bubonic  plague  (the  most  common  form);  (2)  the  cutaneous  form 
(formation  of  vesicles  and  ulcers  or  furuncle-like  inflammations);  (3)  the  pulmonary 
form;  (4)  the  intestinal  form. 

Through  the  investigations  of  Ducrey,  Krejting,  and  Petersen  (cf.  Petersen,  "  Ulcus 
Molle,"  Arch.  f.  Derm.,  xxix.,  1894;  xxx.,  1895,  and  Babes,  "  Handbuch  d.  pathog.  Mi- 
kroorg.,"  iii.,  1903)  it  is  probable  that  the  ulcus  mnlle  or  soft  chancre  is  caused  by  a 
bacillus.  Tomasczewski  ("  Der  Erreger  des  Ulcus,"  Z.  f.  Hyg..  42  Bd.,  1903)  has  demon- 
fitrated  through  self-inoculation  that  a  typical  ulcus  molle  can  be  produced  with  cultures, 
grown  upon  blood-agar  or  blood.  The  bacillus  is  non-motile,  does  not  stain  with  Gram's, 
and  often  forms  chains.  (See  also  "Observations  on  the  Distribution  and  Culture  of 
the  Chancroid  BaciUus,"  by  Davis,  Jour,  of  Med.  Res.,  1902). 

Some  years  ago  Sanarelli  ("  Sur  la  fievre  jaune,"  A?m.  de  Vlnst.  Pasteur,  1897; 
Cent.  f.  Bakt.,  xii.)  described  as  the  cause  of  yellow  fever  a  bacillus  whose  proper- 
ties he  sought  to  determine  by  means  of  culture-experiments  and  animal-inoculations. 
He  is  still  of  the  opinion  that  his  Bacillus  icteroides  is  tiie  cause  of  yellow  fever  ("  Zur 
Lehre  vom  gelben  Pleber,"  Cbl.  f.  Baki.,  xxvii.,  1900),  and  reports  favorably  of  the 
l>rotective  and  curative  effects  ("  Exper.  sur  I'emploi  du  serum  curatif  et  preventif 
de  la  fievre  jaune,"  Ann.  de  VInst.  Pasteur,  1898)  of  his  .serum  obtained  from  vac- 
cinated animals  (dogs,  horses,  cattle).  Freire  ("Man.  sur  la  bacteriologie,  pathogenie 
et  traitement  de  la  fievre  jaune,"  Rio  de  Janeiro,  1898,  Cbl.  f.  Bakt.,  xxvi.)  on  the 
other  hand  opposes  energetically  the  correctness  of  Sanarelli's  views,  and  maintains 
tiiat  the  cause  of  yellow  fever  is  a  coccus  earlier  described  by  him,  which  he  calls  the 
Micrococcus  .ronthogenicus.  Bandi  {" Aetiologie  und  Pat hogenese  des  gelben  Fiebers,'* 
Z.  f.  Hyg.,  46  Bd.,  1904)  favors  the  pathogenic  significance  of  the  Sanarelli  bacillus. 
It  is  very  probable  that  neither  Sanarelli's  bacillus  nor  the  coccus  described  by  Freire 
has  any  etiological  relationship  to  yellow  fever.  It  is  much  more  likely  that  the  cause 
will  be  fovmd  among  the  protozoa,  since  the  pathogenesis  corresponds  more  to  that  of 
malaria  and  infection  with  trj-^^anosomes.  (See  these.)  Other  writers  {Novy)  sug- 
gest that  the  etiological  agent  of  yellow  fever  may  be  found  to  belong  to  the  spirilla. 

Literature. 

{Plague.) 

Abel:   Geschiclitliches  fiber  die  Rattenpest.     Zeitschr.  f.  Hyg.,  36  Bd.,  1901. 

Albrecht  u.  Ghon:    Ueber  die  Beulenpest  in  Bombay  im  J.  1897,  Wien,  1898,  1900. 

Acyama:   Die  Pestepidemie  im  Jahre  1894  in  Hong-Kong,  Tokio,  1895. 

Babes:   Durch  Pestbacillen  verursachte  ^'er;iuderungen.     Virch.  Arch..  150  Bd.,  1897. 

Bitter:   Schutzimpfungen  gegen  Pest.     Zeitschr.  f.  Hyg.,  30  Bd.,  1899. 

Dowel:   EmpfangUchkeit  d.  Frosche  f.  Beulenpest.     Cbl.  f.  Bakt.,  xxii.,  1S97. 

Dieudonne:  Pest.     Handb.  d.  path.  Mikroorg.,  ii..  Jena.  1903  (Lit.). 

Dlirck:    Beitr.  z.  path.  Anat.  d.  Pest.     B.  v.  Ziegler,  Suppl.  vi..  1904. 

Flexner:   The  Pathologv  of  Bubonic  Plague.     Univ.  of  Penn.  Med.  Bull.,  1901. 

GafFky,    Pfeiffer,  Sticker  u.  Dieudonne:    Pest.     Arb.  a.  d.  K.  Gesundheitsamte^, 

\vi.,  lS't<). 
Herzog-:  The  Plague.     Rep.  of  Gov.  Laboratories,  Manila,  1904,  1905. 
Kitasato:  Pr(4iniinary  Note  of  the  Bacillus  of  Bubonic  Plague,  Konsr-Konir,  18!t4. 
Koch:  Vcrbreituugd.  Beulenpest.     Deut.  med.  Wocli..  1898. 
KoUe:  Bakteriologie  der  Beulenpest.     Deut.  med.  Woch.,  1897. 
Lustig:  Gewebsverilnderungen  bei  Beulenpest.     Cbl.  f.  allg.  Path.,  viii.,  18!tT;  Siero- 

tcrapia  e  vaccina/.if)ni  preventive  contro  la  peste  bubonica,  1897. 
Markl:  Pesttoxine.     Cbl.  f.  Bakt.,  xxiv.,  1898. 
Metschnikoff:  La  peste  bubnniciue.     Ann.  de  I'lnst.  Pasteur,  1897. 
Miiller  u.  Pooh:  Die  Pest,  Wien,  1900. 
Netter:   Lc  microbe  de  la  peste.     Arch,  de  med.  exp.,  litcO  (Lit.). 


iJACILLl  S     I  rnKHClLOSIS.  01.") 

Nuttall  u    KoUe:   Die  Tnsektcubci  (IcT  Pes;.     Cbl.  f.  Bakt..  x\ii     isflT 

Sata:  Actiologie  u.  Auat.  d.  Pest.     Anh.  t.  Ihi:..  ii7.  8!»  I5il..  liMIO,  liMil 

Schsube:  Pest.     Eulcnb.   Rcaleiicyklop..   lS!n';'l)ic  Kraiikhcil.ii  d.  \v;.rmrii   Liiiidcr. 

Jciia.  1!)03. 
Schottelius:  Die  Buboiiciipcst  in  I'.omhax .     Ilvuifii.  ituiidscliau,  1901. 
Simond:   La  iimpauatioii  dc  la  pcslc.     Ann.  dc'l'Insi.  Pasicur.  ISUH. 
Wyssokowitz  (I  Zabolotny:  Pccli.  sur  la  pest c.     Ann.  de  I'lnst.  Pasteur,  1897. 
Yamagiva:  Die  J5ul)(uienpest.     Vireli.  Areli.,  14i»  Bd..  Supjil.,  IMlT. 
Yersin:  8ur  hi  i)este  liuhonitiue.     Ann.  de  TJnst.  I'astenr.  1S!»4,  IS'.)?. 
Zettnow:  Bacillus  iler  Bubonenpest.     Zeitselir.  1'.  lly.i;..  .\\i.,  isi»(». 

§  170.  The  Bacillus  tuberculosis  istlu' caii.sc  of  the  iiiiVclioiis  (lis('as(> 
oceiiiTing  so  froqiioiilly  in  man  aiul  Uic  (loincslic  aiiinial.s  wliicli  i.s  kiKtwn 
ordinarily  as  tuberculosis,  bul  is  also  soiiictiincs  called  jirarl  <lis,((xr 
(PetisKcht)  iu  animals. 

Tlu'  tiibercle-bacillnsAvas  discovi'icd  and  1  lior(»u.«ilily  sliidicd  l>y  Kocii 
ill  1882.  It  is  a  slender  rod  (Fig.  4G4\  of  1.5-4 //."in  Ien<;lh,  and  is 
usually  slightly  curved.  It  may  be  stained  by  aniline-dyes  (fnelisin. 
gentian-violet)  to  an  aqueous  solution  of  wlueli  an  alkali,  or  caibolic 
aeid,  or  aniline  oil  is  added.  The  bacilli  when  once  stained  ictain  the 
stain,  even  wheu  the  preparation  is  decolorized  in  dilute  sul|>luiric  acid. 
or  nitric  acid,  or  hydrochloric  acid  and  alcohol. 

The  stained  bacilli  not  infrequently  show  in  their  interioi'  clear,  shin- 
ing, unstained  areas,  or  are  composed  of  little  stained  spherules.  Kodi 
formerly  regarded  these  clear  spots  as  spores,  and  this  view  was  generally 
accepted  for  a  long  time.  Nevertheless,  a  germination  of  these  slriic 
tares  could  uot  be  demonstrated,  and  at  the  pres«Mit  time  they  are  no 
longer  regarded  as  spores.  Con.sequently,  the  tnbeicle-bacilli  foim  no 
special  resistant  forms,  but  on  the  other  hand  the  bacilli  are  more  resist- 
ant against  external  influences,  foi-  example,  against  drying,  than  are 
many  other  bacteria. 

The  tubercle-bacilli  may  be  cultivated  at  the  body  tem])era(nre  and 
ill  the  presence  of  oxygen  upon  coagulated  blood-.serum,  blo(»d-serum- 
gelatin,  nutrient  agar,  and  in  liouillon.  They  increa.se,  howe\er,  very 
.slowly,  .so  that  only  on  the  seventh  to  tenth  day  or  even  later,  dct  the  cnl 
tures  become  visible  in  the  form  of  dull-white  tlakes  resembling  little 
scales.  Larger  cultures  form,  on  llie  snrface  of  coagulated  blood  serum, 
\\liitish,  irregidarly  shaped,  Instreless  deposits.  According  to  Xocar'(l, 
K'oux,  and  Jjischolf  the  growth  of  the  bacilli  is  gr<'at  ly  aided  by  the 
addition  of  glycerin  (four  to  eight  per 
cent).  In  cnltures  the  tubercle-bacilli 
also  foi-m  threads,  which  in  part  show 
branching. 

At  temperatures  below  28°  C.  and 
a])0ve  42"  ( '.  the  growth  of  the  bacilli 
cea.ses.  Sunlight  kills  the  bacilli  in  a 
short  time  (Koch). 

If  the  bacilli  from  pure  cultures  are 
inoculated  into  experimental  animals, 
tubercnlo.sis  is  produced  in  these;  ami 
the  infection  is  transmitted  as  well  bv 
uioculation   under  the  skin,  or  into  tlie    „  ,„an  siirr.-rinjf  with  pu nary  i -rru- 

lieritoiu^'il    r-i\it^-     nv  lli<»  ■iiifoiidi-  cli-ini-     '"'*''*■      ^ iir-prfpiinitimi  on    <<)MT-»fliis.s. 

"iiiontai   c<l^lI^,  oi  iiie.niHiioi  (  n.im     ^,,,(,,^,1  win,  fu.ij.->iii  una  in.-ihvi.Mir-i.iu.'. 
bei- of  the  eye,  as  also  l)y  iidialation  of    x  41x1. 
an  atomized  susi)eusion  of  the  culture, 

by  feeding,  and  by  injection  of  bacilli  into  the  vj'in.s.      In  experimental 
feeding  success  is  often  attained  only  after  long  adminisualion  of  Hm- 


-  4 

1 

GKj 


THE    PATHOGENIC    FISSIOX-FrXGI. 


biicilli,  since  not  every  bacillus  gaining  entrance  into  the  intestinal 
h-act  leads  to  infection.  It  is  also  true  that  bacilli  lodging  upon  the 
mucous  membrane  of  the  respiratory  tract  do  not  always  succeed  in  grow- 
ing in  the  tissue.  Guinea-i^igs,  rabbits,  cats,  and  gray  field  mice  are 
»si5ecially  susceptible;  dogs,  rats,  and  white  mice  less  so. 

Infection  of  man  and  of    animals    occurs   from  the  taking  up  of 
tuberck^-bacilli  from  the  lungs,  respiratory  passages,  and  the  intestinal 

tract,    or   from   wounds 


.  ^  c:  -:-  'o  ^'-^  ^^ 


and  tissue  -  ulceratimis. 
In  the  alimentary  tract 
the  lymphadenoid  ap- 
paratus, tonsils,  and  the 
intestinal  lymi)h  -  fol- 
licles form  the  most  f le- 
quent  avenue  of  en- 
trance. Xurslings  aie 
particularly  susce|>ti] )le 
to  intestinal  infection. 
Further,  a  direct  trans- 
mission of  the  bacilli 
from  the  mother  to  the 
foetus  in  ^dero  may  occur, 
but  this  is  rare.  A  mul- 
tiplication of  the  bacilli, 
that  is,  the  productidu 
of  tul)erculosis,  occurs 
usually  at  the  points  of 
entrance  of  the  bacilli, 
but  may  also  occur  only 
after  the  transportation 
of  the  bacilli  through  the  blood  or  lymph,  so  that  hoematogenous  or 
lymphogenous  disease  of  the  internal  organs,  for  example,  of  the  lymi)h- 
glands,  bones,  brain,  and  tubes,  may  occur  as  the  primary  localization. 
The  bacilli  are  spread  throughout  the  external  world  chiefly  by  the 


^^fS^'i^"^^"" 


Fig.  46o.— Tubercle  from 
fluid,   Bismarck  lirowii). 
lymphoid  cells.    X  M). 


fuiiffous  frranulatioii  of  hone  (Miiller's 
,   Giant-cell;    h,  epithelioid  cells;    c, 


F;<j.  4r>6. -Giant-cell  containing  bacilli,  and  showing  necrotic  centre,  from 
gentian-violei  and  vesuvin,  mounted  in  Canada  balsam. 


Stain. -il  with 


.«^puta,  under  certain  conditions  also  by  the  ffeces  and  urine,  further  frc.m 
tuberculous  ulcers,  or  from  tuberculous  organs  which  are  taken  from 
living  or  dead  per.sons.  Since  the  bacilli  are  rather  resistant,  they  may 
be  preserved  outside  of  the  animal  body  for  a  long  time  under  certain 
conditions,  and  may  become  mixed  M'ith  the  respired  air,  as  well  as  with 


BACILLI  S    'PrHF.KCMLOSIS.  ',17 

the  food  and  drink.     The  milk  of  t iihci-ciiloiis  rows  contnins  llir  l):icilli 
especially  when  the  udder  is  diseased  ;  but  lin-  Ivu-illi  miy  also  j.a^s  into 


Fig.  467.— Tuberculosis  of  the  pleuia  (alcohol.  Van  (iicsoirs).    n.  TliirkciiiMl 
tubercle  with  giant-celis  ;  c,  deposit  i>f  tlbnn.         ~( 


(lifcrating  pleura ;  7», 


the  milk  Avhen  no  disease  of  the  udder  eau  be  dcmonsl  rated  (iliiseiibei-j;, 
Ernst,  Leuch). 

If  the  bacilli  succeed  in  developing-  and  mnlti])l>  iiig-  in  any  tissue  of 
the  human  body,  they  lead  by  a  series  of  chanoes  to  the  formatiou  of 


^     ^-^ 


M 


^--im^m^p^'^r^d^ 


^x> 


'&^:  J^.:0^^^1£^^^ -'^^^ 


Fig.  IfiS.— Large-celled  tubercle  rontainiii-rllhrin.  from  a  tiil>erculoujj  hint' 
?j,  glauU'ell ;  c,  larKe-celled  tissue.     ,  :j(K 


ihul.niirin-staliii 


iwdular  masses  of  ffrauutaf ion  fi-s.siir  nv  tubercles,  wliieli    remain  «le\(>id   of 
hlood-vesseJs,  and  after  reach  in  <;•  a  eei-tain  stage  of  (ii-xclopment    nmleigo 


CIS 


THE    PATHOGENIC    FISSIOX-FUXGI. 


W' 


)'etrog:ressive  clumiies.     Tlie  formation  of  the  nodule  may  be  accompanied 

by  a  more  or  less  extensive  intlammatory  exudation. 

The  first  effect  of  the  development  of  the  bacilli  in  a  tissue  is  a  ii,sfiiie- 

degeneration,  in  Avhich  the  tissue-cells  as  well    as  the  connective-tissue 

gTound-substance  over  a  laroer  or 
smaller  area  are  destroyed.  To  the  de- 
generative processes  there  is  added  theu 
on  the  one  hand  an  intlammatory  exu- 
dation— ^that  is,  emigrdtion  of  leucocytes 
(did  /i/mphoci/te.s — and,  on  the  other  hand, 
ii  J) rol if erat ion  of  the  ti)i.sue-eeUs  remaining 
2>reserved  within  the  affected  area  (Fig. 
465,  a).  The  degree  of  the  exudative 
X)rocesses  in  the  region  of  the  nodule 
varies  and  is  dependent  upon  the  luim- 
ber  and  the  virulence  of  the  bacilli  pres- 
ent in  the  tissne  and  also  upon  the 
mode  of  infection.  When  a  large  num- 
ber of  bacilli  are  introduced  into  the 
lung  through  the  respiratory  tract  the 
exudative    intlamnuition    is    very    pro- 

nunnced.     It  is  less  marked  in  the  case  of  the  inti'odnction  of   bacilli 

into  the  liver  through  the  portal  vein. 

The  cells  of  the  exudate  tii'st  appearing  are  (•\\wi\x })olii nuclear  leucocytes, 

but  later  mononuclear  li/m]>hoc/ffe.s  and  leneoeytes  ])r('(lominate.      The  appear- 
ances of  jjro?//V'>v^//o»  may  be  shown  by  the  second  day. 

The  cellular  nodule  M'hich  after  the  course  of  a  few  days  represents  the 


Fig.  469.— (  astoiN  netroMs 
lous  granulation  tw^ni  (iI'dI 
aniline  blue),  a  (iimiilu  ((, 
ous  masses;  7)  fihi  d  lliil  u  ii-- 
cell  with  bacilli,  d  ImoiIi  iiki 
p,  bacilli  in  neciotu  ti>"-ut 
closed  in  cells     x  -(Hi 


)f  tubeuu 

1       fUfllMFl 


■'  ']'■ 

% 

•::;>.• 

;.;;V*^-::>'V' 

■^n 

'.  *-*X 

•S/v^-''- 

'.;  i-y'ryA^-^ 

i. '■■■'■•■■■ 

■W 

«i^% 

';!; 

t 

,-V  VJ 

A^l 

W'-Y''l 

'%:■ 

m 

mi 


Fig.   470.— Section  of  miliary  tubercle  of  tlie  omentum  (alcohol,  hcCiuutuxvlin,  eosin).    o,  Caseous  centre 
containing  remains  of  fat-cells ;  h,  flbrocellular  periphery ;  c,  gianl>cells ;  d,  fat  tissue.    X  UX). 

tubercle  at  the  height  of  its  develojunent  shows  usually  three  types  of 
cells — large  epithelioid  cells,  irith  clear  nuclei  (Fig.  4G5,  h),  niultinnclear 
(jiant-celh  (a),  ami  li/nijdioeytes  (c).    The  first  two  forms  are  found  particu-  [1 


TriiiOHClLOSIr 


01'.) 


l:irly  in  tho  ctMitrnl  \r.\vi  of  tlic  1ii1km-cU',  tln'  latter  at  tin'  pcriplKMy.  'IIic 
iiiinihcr  of  the  iiulividual  cell-foiiiis  \  arit's,  and  under  cci tain  conditions 
tlie  lymphocytes  may  be  so  numerous  as  greatly  to  o\  ('rsIiado\\  the  larger 


Fift.  471.— Fibrocaseoiis  ti 
homogeneous  connective  li.ssii 


I.  luun  tissue.     X  XO. 


cell-forms.     On  the  other  hand,  at  oilier  tiiiH's  tlu'  ('pithelioid  cells  with 
lightly  staining;-  nuclei  inay  predominate,     ^j'hese  cells  are  in  part  changed 


fr.v. 


■^^mm':-- 


&&. 


Fig.  472.-l''ibrous tubercle  in  the  thickened  synovial  memhnine  of  the  knee-joint  (iiIcoh<.l.  h;i'riiain.\>llti, 
picric  acid,  fuchsin).    o.  Connective  tissue  ;/<,  c,  (/,  llhn.us  tul)en-Ie.     :■'  ,;•. 

lymphocytes  arising  from  the  blood  (polyblasts)  ;    in  pait    lihrublasts 
arising  through  the  proliferation  of  connective-tissue  cells  ///  lin-,,. 

Tlie  giant-eells belong  nsnally  to  the  sync.xtial  l\  i»e  and  arise  tlnou-h 


620  THE    PATHOGENIC    FISSIOX-FUXGI. 

the  confluence  of  cells,  but  it  is  also  possible  that  they  arise  through  the 
multiplication  of  tlie  nucleus  in  a  single  cell.  The  nuclei  lie  usually  in 
the  peripheral  portion  of  the  protoplasmic  mass  (Figs.  405,  a,  and  46G) ; 
sometimes  collected  at  one  pole,  sometimes  at  both  poles;  sometimes  ar- 
ranged in  a  wreath  or  in  a  crescent.  They  often  contain  luuuerous  bacilli 
(Figs.  40(>  and  469,  c).  The  non-nucleated  portion  of  the  protoplasm 
may  often  be  recognized  to  be  ^hanged,  degenerated,  or  necrotic  because 
of  its  reaction  toward  stains  (Fig.  466). 

Through  the  proliferation  of  the  cells  the  remaining  connective-tissue 
stroma  of  the  original  tissue  is  pushed  farther  and  farther  apart,  so  that 
the  individual  cells  come  finally  to  be  separated  from  one  another  only 
by  scanty  fibres,  Mhose  general  arrangement  is  in  the  form  of  a  net- 
work, which  is  consequently  called  the  reticulum  of  the  tuherele. 

New  vessels  are  not  formed  Avithin  the  tubercle;  and  the  old  i-essels  are 
closed  through  the  proliferation  of  the  vessel -walls.  Usually  the  new  forma- 
tion of  connective  tissue  stops  with  the  production  offbroblasfs. 

The  neighborhood  of  the  tubercle  xiro^ier  may  show  no  essential 
change,but  usually  presents  the  appearance  of  an  inflammation,  particu- 
larly a  small-celled  tissue  infiltration  or  proliferation  (Fig.  4(57,  a). 

A  serous  exudation  is  also  usually  associated  with  the  cellular  emi- 
gration, and  fibrin  may  be  formed  both  within  the  tubercle  itself  (Fig.  468.  a) 
and  in  its  neighborhood  (Fig.  467,  c). 

At  the  height  of  its  development  the  tubercle  forms  a  small,  grai/, 
translucent  cellular  nodule,  which  may  reach  the  size  of  a  millet-seed,  and 
encloses  in  its  tissue  tubercle-bacilli  in  larger  or  smaller  numbei-s.  When 
it  has  reached  a  certain  size  retrogressive  changes  usually  appear  in  its 
centre,  the  tubercle  in  consequence  becoming  cloudy,  opaque,  and  of  a 
white  or  grayish -white  or  yellowish -white  color — these  changes  being  desig- 
nated as  caseation. 

The  caseation  of  the  tubercle  is  dependent  on  the  one  hand  upon  a 
necrobiosis  of  the  cells,  and  on  the  other  upon  the  deposit  of  coagulated  sub- 
stances in  the  spaces  between  the  cells.  The  cell-necrosis  is  characterized 
by  a  loss  of  the  nuclei  and  a  transformation  of  the  cells  into  lumpy 
masses  which  later  disintegrate  and  become  granular  (Fig.  460.  «,.  a). 
The  deposit  between  the  cells  consists  either  of  a  network  of  fibrin  (Fig. 
468,  «)  or  of  a  granular  or  hyaline  reticulated  fibrinoid  substance  resem- 
bling fibrin  but  which  does  not  take  the  Weigert's  fibrin  stain  and  is 
stained  yellow  by  Van  Gieson's.  In  the  further  course  of  the  process  of 
caseation  the  fibrin  and  fibrinoid  substance  disintegrate  into  a  granular 
mass  which  fuses  with  the  cell-detritus,  so  that  the  central  part  of  the 
tubercle  consists  of  a  huupy  granular  mass  (Figs.  469,  a,  471,  a)  which 
takes  a  weak  diffuse  stain  with  nuclear  stains. 

The  caseation  aft'ects  at  first  the  central  portion  of  the  tubercle,  and 
is  usually  confined  to  this,  while  connective  tissue  is  formed  at  the  per- 
iphery, so  that  the  tuherele  comes  to  consist  of  a  caseous  centre  (Fig. 
470,  a)  and  -a  fibrocellular  periphery  (b)  which  usually  contains  giant-cells. 
Under  certain  conditions  the  caseation  may  involve  the  entire  tubercle. 
If  the  caseation  does  not  affect  the  periphery,  the  fibrocellular  tissue  of 
the  peripheral  zone,  sooner  or  latei-,  l)ecomes  transformed  into  a  pure 
fibrous  tissue,  so  that  a  fibrocaseous  tubercle  (Fig.  471,  a,  b)  is  formed, 
the  connective  tissue  of  which  is  coarsely  fibrillar  or  hyaline  and  poor  in 
cells  (6),  and  in  the  course  of  time  usually  becomes  sharply  defined  from 
the  caseous  centre  (a),  so  that  the  latter  appears  to  be  encapsulated  by 
connective  tissue.     If  the  tuberculosis  runs  a  favorable  course  the  cen- 


Tl'BERCULOSIS.  02 1 

ti-e  iiistond  of  oaseatiiiji;  may  iiiuTergo  a  connect ivo-t  Issue  nictanuirpliosis 
(  Fiii".  472,  h,  c,  d),  so  that  llic  tnluTclt'  becomes  ('lian.m'd  into  a  fibrous 
nodule. 

The  inf(Cfii»(s  initinr  of  tlu'  disease   kiidwii  -as  ti/licrciloKiK  hud   already  1 n  deler- 

niiiu'd  by  the  cxperimoiital  traiisiiiission  of  tuljeicidosis  to  aiiiiiials  {Vilitniin.  I.tlnit, 
ir,V.s-.v,  Cohnheiin,  Khbs,  Laiif/hidis.  and  oUrts).  betore  tlit-  discovery  of  the  tnlu'ieh-- 
baeilUis.  Nevertheless,  it  was  a  long  time  before  the  view  tiiat  tubrrctdosis  was  au 
infectious  disease  received  general  acceptance,  and  opposition  to  this  view  has  even  to- 
day not  wholly  disappeared  (Jfiddendorp). 

The  peculiar  behavior  of  the  tubercle-bacillus  toward  stains— tiiaf  is.  its  property 
of  retaining  the  stain  after  treatment  of  the  preparation  witli  neids  and  alcoliol,  I  lie  sd- 
called  acid- and  ((Icolml-resiHtdiice — makes  it  jiossihle  to  demonstrale  wiih  relati\eease 
the  presence  of  tubercle-bacilli  in  the  s|niium  or  in  tiie  tissues,  and  to  ditl'erenliate  it 
from  other  bacteria.  It  should  be  noted,  however,  that  other  bacteria  siiow  tliese  jirop- 
erties;  X.\w  JntriUun  of  lepros}/.  t\w  >iiiit'f/iii<i-b<tr/7/i/s  (a  bacillus  very  fre<iuenlly  found  on 
the  corona  glandis,  between  the  scrotum  and  thigh  and  in  the  folds  between  the  labia 
niajoraand  minora),  further  two  dilTcrent  bttrilli  fmiiiil  in  hutti  /•(onedeseribed  by  I,.  R(di- 
iii'uritsch  and  Petri,  the  other  by  Korn).  and  finally  also  dillVrent  bacilli  cultivated  by 
Miiellev  from  .v/v/.y.v<.v  (timothy-grass)  and  from  I'liw-dniKj.  All  these  acid-resisting  bacilli 
may  under  certain  conditions  lead  to  errors  of  diagnosis;  for  example,  the  smegma- 
bacillus  in  the  examination  of  urine,  the  buttcr-baciili  in  the  examination  of  butter,  the 
latter  particularly,  since  the  bacillus  described  by  Rahinoiriisch.  when  injected  into  the 
peritoneal  cavitv  of  guinea-pigs,  causes  a  disease  of  the  alxlomen  .-similar  to  true  inocu- 
lation-tuberculosis, while  the  bacillus  described  by  Korn  causes  a  )>seudotuberculosis  in 
white  mice  (these  animals  sho-nnng  but  slight  susceptibility  to  true  tuberculosis). 
Acid-fast  bacilli,  which  probably  represent  a  variety  of  the  Habinowit.sch  butter  bacil- 
lus, have  been  found  in  gangrenous  foci  in  the  lung  (Rabinotvitsch)  as  well  as  in  the 
sputum  of  cases  of  pulmonary  gangrene  (jPo//(',  .1/o/ycr,  Op/; (V/s,  Birt  and  Leishrnan). 
Moeller  has  found  acid-fast  bacilli  in  nasal  and  pharyngetd  mucus. 

Since  the  tubercle-bacillus  in  cultures  forms  simple  and  branching  tlireads  {Klein, 
Fischel,  Coppen-Jones,  Xocard,  Maffucci,  and  others)  and  bud-  and  dub-like  swellings, 
many  authors  are  inclined  to  group  it  with  the  thread-fungi.  Lchmann  and  Xeumann 
designate  it  as  Mycobacterium  tubcrcul()si.<<,  Cuppcn-Joncs  as  Tubcrculomi/ccs. 

Since  the  tubercle-bacillus  in  caseous  pulmonary  foci  {('()])pcn-Joncs),  and  after 
direct  injection  into  the  parenchyma  of  the  brain,  kidneys,  manunary  glands,  and  testi- 
cles, as  well  as  after  the  intra-arterial  injection  of  large  numlx'rs  of  bacilli  (Babes,  Leva' 
diti,  Schulze,  Lubarsch,  Friedrich,  and  Xcisske)  forms,  in  addition  to  the  ordinary 
colonies  of  bacilli,  fungus-masses  also  resembling  those  of  actinomyces,  on  the  outer 
surface  of  which  ray-like  clubs  radiate  into  the  surrounding  tissue,  Lul)arsch  and  others, 
in  the  assumption  that  the  fungus-masses  consist  of  branching  threads,  have  clas.sed 
the  tubercle-bacillus  with  the  actinomyces  or  ray-fungi.  Lubarsch  regards  the  ray- 
fungi  as  a  sub-class  of  the  Streptothrices,  an  intermediate  group  lying  between  the 
Schizomycetes  and  the  Hyphomycetes,  and  characterized  by  the  formation  of  clubs; 
and  to  this  class  he  assigns  also  the  butter-  and  dung-fungi  mentioned  above.  Accord- 
ing to  Friedrich  and  Xusske  the  fungus-masses  regarded  as  resembling  those  of  actino- 
myces consist  only  of  rods. 

According  to  the  investigations  of  Hammerschlag,  RuppeJ,  Sata,  and  others,  the 
tubercle-bacilli  contain  an  abundance  of  fat,  which  under  jiroper  conditions  nuiy  bo 
demonstrated  by  staining  with  sudan  (Sata).  According  to  Ilaminrrsrhla;/  the  tubercle- 
bacilli  contain  twenty-seven  per  cent  of  substances  .soluble  in  alcohol  and  ether  (fats, 
lecithin,  poistmous  substances),  while  other  bacteria  contain  oidy  1.7-10  ix-r  cent  of 
the  same.  The  remaining  substance  insoluble  in  alcohol  contains  albumin  and  celhi- 
lose.  Apparently  the  acid  resistance  of  the  bacilli  is  dependent  ui>on  tiie  rich  fat 
content,  young  bacilli  which  lack  the  fat  covering  are  not  a_ci<l-fast  {Mttrinorck). 

According  to  the  investigations  of  Pruddcn,  Ilodenpyl,  Ko.strnitsch,  \'lssinaun,  .^fa- 
sur,  Kockel,  and  others,  dead  tubercle-bacilli,  when  introduced  into  the  ti.ssues  of  an 
animal  by  inoculation,  or  injection  into  the  blood-stream,  or  tiirough  introduction 
into  the  respiratory  passages,  excite,  at  the  i)oint  of  deposit,  infianunation  and  ti.ssuc- 
proliferation  similar  to  that  caused  by  living  bacilli,  and  in  tiic  ca.se  of  a  large  inocvi- 
tation  may  lead  also  to  suppuration.  These  changes  differ,  however,  from  tho.se  i)ro- 
duced  by  living  bacilli,  in  that  the  bacilli  are  destroyed  after  a  few  weeks  and  the 
nodules  of  granulation  tissue  heal  through  a  transformation  into  hbrous  tissue;  and 
further,  by  the  fact  that  the  severity  of  the  local  tissue-proliferation  is  dependent 
wholly  upon  the  amount  of  dead  bacilli  introduced,  and  that  there  is  no  spread  of  the 
process  throughout  the  body.  The  dead  bacilli  must  therefore  contaui  substances 
(proteins)  which  cause  inflammation  and  later  also  tissue-proliferation. 


022  THE    PATHOGENIC    FISSION-FUNGI. 

In  addition  to  the  local  effects,  the  substance  contained  in  the  cell-bodies  of  the 
bacilU  may  also  cause  emaciation  of  the  animal. 

The  active  substance  of  the  bodies  of  the  hacilli — tuberculin — was  first  produced  by 
Koch  (1890)  from  six-  to  eight-weeks-old  cidtures  in  a  weak  alkahne  veal-infusion,  to 
which  one  per  cent  of  peptone  and  four  to  five  per  cent  of  glycerin  were  added,  by 
evaporation  upon  a  water-bath  to  one-tenth  of  the  original  volume  and  filtering  through 
a  filter  of  earthenware  and  silicious  marl.  Later  (1897)  he  dried  highly  virulent  cult- 
ures of  tubercle-liacilU  in  a  vacuimi-exsiccator,  then  triturated  the  dry  substance, 
mixed  it  with  tUstilled  water  and  centrifugated  it.  The  active  principle  ij  contained 
in  the  muddy  precipitate  thus  obtained,  which  is  again  dried  and  triturated  and  dis- 
.solved  in  water  to  which  twenty  per  cent  of  glycerin  is  added  for  the  purpose  of  pres- 
ervation. This  tuberculin  (designated  by  Koch  as  T.  R.)  is  said  to  contain  lOmgm. 
of  solid  substance  in  1  c.c.  (prepared  by  Meister,  Lucius,  and  Bri'mning). 

Whether  the  tubercle-bacilh  produce  a  true  toxin  is  a  question  that  has  not  yet 
been  decided,  but  tliis  is  probably  not  the  case;  and  in  favor  of  tliis  is  the  fact  that 
localized  tuberculosis  clinically  shows  no  symptoms  of  intoxication.  The  tuberculins 
obtained  by  various  methods  contain  a  mixture  of  different  substances  which,  like  the 
substances  derived  from  other  bacteria,  excite  inflammation.  Perhaps  they  contain 
also  specific  albumin  bodies  which,  in  the  organism,  cause  the  production  of  specific 
bactericidal  protective  forces,  either  througli  the  formation  of  bacteriulysins  or  of  agglu- 
linins  and  precipitins  that  act  upon  the  bacteria.     (See  §  33.) 

Through  the  investigations  of  Arloing  and  Courmont  we  know  that  an  emulsion 
of  cultures  of  tuber cle-bacilli  grown  upon  potatoes  is  agglutinated  by  the  serum  of 
tuberculous  men  and  animals.  Through  an  especial  method  Koch  has  prepared  a 
fluid  containing  l)acilli  in  which  a  clouding  and  a  flocculent  precipitate  is  produced  by 
an  agglutinating  scrum.  The  serum  of  healthy  animals  (rabbits,  dogs,  cow,  and 
donkey)  shows  no  agglutinating  action  when  the  test  fluid  is  added  to  the  serum  in 
the  proportion  of  1:25;  yet  there  are  exceptions  to  tliis  and  liorse  serum  usually 
shows  an  agglutinative  power.  According  to  Koch  and  Romberg  the  serum  of  children 
possesses  no  agglutinative  power.  After  tlie  fourteenth  year  it  is  very  frequently 
present,  probably  as  the  result  of  latent  tuberculosis.  Through  the  treatment  of  an 
animal  with  dead  or  living  cultures  of  tubercle-bacilli  it  is  possible  to  produce  a  serum 
capable  of  agglutination  {Koch)  or  to  increase  that  already  present,  particularly  easily 
in  goats  and  donkeys. 

Animals  possessing  the  power  of  agglntination  show  a  more  or  less  high  degree  of 
immunity  against  an  artificial  infection  with  tubercle-bacilli,  and  the  agglutinative 
power  may  therefore  be  regarded  as  an  indication  of  the  existence  of  protective  sub- 
stances. 

In  men  suffering  from  tuberculosis  the  power  to  agglutinate  is  not  usually  shown 
In  dilutions  of  1 :  25.  In  advanced  tuberculosis  the  agglutination  power  is  usually 
"^anting,  since  in  the  course  of  a  malignant  tuberculosis  the  protective  substances 
are  either  not  formed  at  all  or  at  least  only  in  small  amounts.  A  mixture  of  pulver- 
ized tubercle-bacilli  in  100  parts  of  water  plus  100  parts  of  glycerin  wlien  injected  in 
increasing  doses  (0.8  per  cent  salt  solution,  the  first  dnse  co.itaius  ().()()25  mg.  of  the 
cell  substance  of  the  bacilli)  has,  in  the  hands  of  Kixh.  iucicuscd  tiie  agglutination 
power  of  numerous  consumptives  (from  1  :  25  to  1: 100  and  1  :  oOO),  so  tliat  it  may  be 
assumed  that  it  is  also  possible  to  produce  in  consumptives  a  certain  amount  of  protec- 
tive substance. 

As  to  the  value  of  the  old  and  new  tuberculin  of  Koch  various  writers  differ.  Its 
worth  as  a  diagnostic  aid  is  not  questioned,  particularly  that  of  the  old  tuberculin, 
since  small  doses  excite  fever  in  tuberculous  animals  but  not  in  healthy  ones,  yet 
there  are  exceptions  also  to  this.  The  old  tuberculin  finds  a  use  in  the  recognition 
and  removal  of  tuberculous  domestic  animals.  As  a  curative  method  (it  is  used  in 
.small  doses  in  tuberculosis)  it  is  praised  by  some,  but  at  present  its  use  is  not  very 
extensive. 

During  the  last  year  much  clinical  interest  has  been  excited  over  the  diagnostic 
use  of  tu])ercuUn  in  the  cutaneous  reaction  ("Pirquet's  reaction  ")  and  the  conjunctival 
reaction  ("Cabnette's  reaction"). 

Von  Behring  has  succeeded  in  rendering  cattle  immune  against  virulent  bovine 
tubercle-bacilli.  He  uses  first  cultures  of  human  tubercle-bacilli  which  are  less  viru- 
lent for  cattle,  and  begins  with  an  intravenous  injection  of  1  mgm.  of  a  serum-cult- 
ure of  a  definite  strength  of  infection.  In  younger  animals  the  immunization  can 
be  much  more  easily  produced  than  in  older  ones.  Von  Behring  regards  it  as  pos- 
sible to  feed  nurslings  with  a  milk  of  cows  made  immune  against  tuberculosis  and 
thus  to  convey  to  them  antibodies  which  may  serve  to  protect  them  from  infection. 


TT^BKHrn.osis.  623 

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Hirschberger:    Jnfoctiositat  d.  .Milcii  tuberkuhiser  Kulio.      Dout.  .\rcli.  f.  klin.   Mod.. 

44  Bd.,  1.S.S9. 
Jani:   Tuberkelbacillen  in  gosundon  ( lowol.on  boi  Lmigonsciiwindsucht.     \'irch.  .\rcli.. 

103  Bd.,  1886. 
Jones:    Moiphologie  u.  systematische  Stellung  d.  Tuberkelpilzos.     Ci)l.  f.  Bakl.,  xvii., 

1S9.-). 
Karlinski:    T'ebortragbarkoit  d.  monschl.  Tuberkulose.     Zoi(s(  luifl  f.  'I'iormrd.,  \  iii., 

1904. 
Kastner:    Boitr.  /..  Infoctiositat  do,  liri,(  Iks  lul.orkul.  ilind.r.      Miincli.  lurd.   Worli., 

1S89. 
Klebs:   Impfversucho.     Virch.  Anli..  4  1,    td   Hd,;     Anli.  f.  oxp.   Path.,   i..   x.,    xvii.; 

Frag.  mod.  AVoch..  1877. 
Koch:    Die  Aotiologie  der  Tul)orkul(.<o.      iiorl.  klin.  Woch..   1S,S2.  \o.   10;     ISS.;.  X... 

10.     Verb.  d.  Congresses  f.   inn.   Mod..   Wio-bad.-n.    |NS2;     .Miltiioil.   a.   d.    Kais. 


G24  THE    PATHOGENIC    FISSIOX-FT'XGI. 

Clesimdhcitsamte,  ii..  Berlin,  1884:    Mittheil.  lib.  ein  Heilmittel  geg.  d.  Tuberkii- 

lose.     Deut.  med.  Woch..  1890:    Mittheil.  iiber  das  Tuberkulin.     lb.,  1891:    Xeue 

Tuberkulinpraparate.     lb.,  1897:  Ueber  die  Agglutination  der  Tuberkelbacillen. 

D.  med.  Woch.,  19U1. 
Kockel:    Histogenese  des  MiUartuberkels.     Virch.  Arch.,  143  Bd.,  1896  (Lit.). 
Korn:   Saurefeste  Bakterien.     Cbl.  f.  Bakt.,  xxv.,  1899;  xxvii.    1900;   Bacillenbefunde 

in  der  Marktbuttcr.     Arch.  f.  Hyg.,  66  Bd.,  1899. 
Kostenitsch :    De  revolution  de  la  tuberculose  par  les  bacilles  morts.     Arch,  de  med. 

exp.,  v..  189;^. 
Kostenitsch  et  WolkoAw:    Rech.  sur  le  developp.  du  tubercle.     Arch,  de  med.  exp., 

iv.,  1892. 
Koster:    Ueber  fungose  Gelenkentziindung.     Virch.  Arch.,  48  Bd.,  1869. 
Langhans:  Die  Uebertragung  der  Tuberkulose  auf  Kaninchen,   1868;    Riesenzelleii 

mit  wandstiindigen  Kernen  in  Tuberkeln.     Virch.  Arch.,  42  Bd.,  1868. 
Lebert    u.    Wyss:     I'ebertragung   der   Tuberkulose.     Virchow's    Archiv,     40    Bil.. 

1S67. 
Levene:   Biochemical  Studies  on  the  Bacillus  Tuberculosis.     Jour,  of  Med.  Research, 

1901. 
Lubarsch:    Zur  Kenntn.  d.  Strahlenpilze.     Zeitschr.  f.  Hyg.,  xxxi.,  1899;   Infektions- 

modus.     Fortschr.  d.  Med.,  1904. 
Maffucci:   Prod,  tossici  del  Bac.  tuberculare.     Policlinico,  ii.,  Roma,  1895;   Die  Hiih- 

nertuberkulose.     Zeitschr.  f.  Hyg.,  xi..  1892. 
Masur   u.    Kockel:   Wirkung   todter   Tuberkelbacillen.     Beitriige   v.    Ziegler,   x^-i., 

1894. 
Menzi:  Zlichtung  u.  Biol.  d.  Tuberkelbacillen.     Z.  f.  Hyg.,  39  Bd..  1902. 
Metsch.nikoff:    Die  phagocvtare  Rolle  der  Tuberkelriesenzellen.     \'ircli.  Arch.,    113 

l^d.,  1888. 
Middendorp:  La  cause  de  la  tul)erculose,  Groningen,    1897;    u.  Consr.  internat.  de 

iiK'd..  Paris,  1901. 
Milchner:    Uebertraguntr  d.  Tul).  durch  Milch  u.  Milchprodvicte.     Zeitschr.  f.  xub., 

i..  1900. 
Miller:   Histogenese  d.  Tuberkels  in  d.  Leber.     B.  v.  Ziegler,  xxxi.,   1902,  n.  J.  of 

Patli.,  X..  1904. 
Morel  et  Dalons:   Histogenese  du  tubercul.     Arch,  de  med.  exp.,  1903. 
Nocai'd.  et  Roux:    Bacille  de  la   tuberculose.     Annales   de   ITnstitut    Pasteur,    xi., 

1897. 
Orth:    Exp.  Unters.  fiber  Fiitterungstuberkulose.     Virch.  Arch.,  76   Bd.,  1876;  Wir- 

kimg  der  Tuberkelbacillen.     Verh.  d.  D.  path.  Ges.,  iv.,  1902:    Entsteh.  d.  Tub., 

Herlin.  klin.  Woch.,  1904. 
Pappenheim:    Histogenese  des  Tuberkels.     Virch.  Arcli.,  169  Bd.,  1902. 
Pawlowsky :   Culture  des  bac.  de  la  tub.  sur  la  pomme  de  terre.     Ann.  de  ITnst.  Pas- 
teur, ii.,  1888;    Entwickekmgsgescliichte  der  Gelenktuberkulose.     Cbl.  f.  Bakt., 

vii..  1890. 
Pertik:    Pathologic   d.  Tuberkulose.    Ergebn.  d.   a.   Pathol.,  viii..  Wiesbaden,   1904 

(Lit.). 
Predohl:   Die  Geschichte  der  Tuberkulose,  Hamburg,  1888. 

Prudden:    A  Study  of  Experimental  Pneimionitis  in  the  Rabbit  Induced  by  the  In- 
fection of  Dead  Tubercle  Bacilli.     New  York  Med.  Journ.,  1891. 
Prudden  and  Hodenpyl:   Action  of  Dead  Bacteria  in  Living  Bodv.     New  York  Med. 

Jour.,  1891. 
Piitz:  Die  Beziehunsen    d.    Tuberkulose    d.  ^Menschen  zur    Tuberkulose  d.    Thiere, 

Stuttg..  1883. 
Rabinowitsch:  Zur  Frage  des  Vorkommens  von  Tuberkelbac.  in   der    Marktbutter. 

Zeitschr.  f.  Hyg.,  xxvi.,  1897;    Deut.  med.  Woch.,  1899;    Saurefeste   Bacillen  bei 

Lungensangran.      lb.,    1900;    Febertragung    d.  Tuberkulose  durch  Milch.     lb., 

1900._ 
Rabino-witsch.  u.  Kempner:    Infectiositat  d.  Milch  tuberk.  Kiihe.     Zeitschr.  f.  Hyg., 

xxxi.,  1899. 
Raymond  et  Arthaud:    Pvccli.  exper.  sur  letiologie  de  la   tul).    Arcli.   sren.   de  med., 

18S3. 
Ruppel:   Ciiemie  d.  Tuberkelbacillen.     Zeitschrift  fiir  phvsikalische  Chemie,  xxvi., 

1S98. 
Sata:   Fettbildung   durch   verschiedene    Bakterien.     Cbl.   f.    allgemeine    Pathologie, 

lOOO. 
Scbieck:    Experiment.   Tuberkulose   der   Kaninchencornea.     Beitr.   v.    Ziegler.    xx., 

1N96. 


TUBERCULOSIS.  02." 

Schmaus  u.  Albrecht:   Die  kiisisio  Xckrose  (iihcrkul.  ( iowcln's.     Viirli.  Aivli.,  Ill 

lid.,  Suppl..  1SU6. 
Sibeley:   The  Nature  of  the   (liant-cvlls   of  'J'uIhtiIc.     .louiii.il  of   .An.itomv.    xxiv., 

lSi»0. 
Sternberg:   Wirkviiii;- toter  Tulu'ikclhacillcn.     (•.•nl  i:ill)l,iii    f   ;ill"<-iiiciiic   l':itliol(iiric 

xiii.,  1902. 
Stock:    Exper.  hiiinatog.    TuberkiUose  cles  Auf^es.     .Monatsclir.    f.   Aimeiiheiik.,    lU-\\., 

1903. 
Straus:    La  tuberculose  et  son  bacillo,  Paris,  189');   Tuberculose  par  iujiestion.     .Vim. 

de  med.  exp..  viii.,  1S9(3. 
Straus  ct  Gamalei'a:   Contrih.  a  I'l't.  du  i>oison  tuhercuh-ux.     .\rcli.  dc  mrd.   exp 

iii.,  1S91. 
Stroebe:   Die  Wirkung  des  neuen  Tuberkulins  T.  R.,  Jena,  1S9S. 
Stschastny:   Formation  des  cellules  geantes,   etc.     Ann.   de  I'liist.    Pasteur,    1SS8- 

Vireh.  Arch.,  115  Bd. 
Tappeiner:    luhalationstuberkulose.     Virch.  Arch..  74,  SJ  lid. 
Tripier:    Ueber  tlen  Bau  der  Miliartuberkel.     Cbl.  f.  allg.  Path.,  i.,  1S9U. 
Veraguth.:   Exp.  Unters.  liber.  luhalationstuberkulose.    Arch.  f.  experim.  Patli.,  xvii., 

1883. 
Villemin:  Gaz.  hebdom.,  1865,  No.  50;  Compt.  rend..  Ixi.,  1866;  lEtudes  sur  la  tulx  i- 

culose,  Paris,  1886;   Etudes  exper.  sur  la  tuberculose,  Paris,  1887-98. 
Vissmann:   Wirkung  todter  Tuberkelbacillcn.     Virch.  Arch.,  129. Bd.,  1892. 
Walther:    Ueber  das  York.  v.  Tuberkeibacillen  im  gesunden  (ienitalapparat  l)ei   Lun- 

genschwindsucht.     Beitr.  v.  Ziegler,  xvi.,  189-4. 
Watanabe:   Wirkung  in  die  Trachea   eingef.    Bacillen.     Beitn'ige   v.    Ziegler,   xxxi., 

1902. 
Wechsberg':    Primare    Wirkung   der   Tuberkeibacillen.     Beitrage    v.  Ziegler,    .xxix., 

1901. 
Weichselbaum :  Bacillen  im  Blute  bei  allgemeiner  Miliartuberkulose.     Deut.  med. 

Woch.,  1884;    Zusammenfass.  Bericht   iib.   d.  Aetiologie   der  Tuberkulose.     Uljl. 

f.  Bact.,  iii.,  1888. 
Welcker:   Phagocytare  RoUe  d.  Riesenzellen.     Beitr.  v.  Ziegler,  xviii..  1895. 
Wesener:    Beitr.  z.  Lehre  v.  d.  Fiittervmgstuberkulose,  Freiburg,  1884. 
Wolff-Eisner:  Die  Ophthalmo- und  Kutandiagnose  der  Tuberculose.     iieitr.  d.  Klinik 

d.  Tuberkulose,  9  Bd.,  1908. 
Yersin:    Etude  sur  le  developpement  du  tubercle  exper.     Ann.  de  I'lnst.  Pasteur,  ii.. 

1888. 
Ziegler:  Ueber  die  Herkunft  der  Tuberkeleleniente,  Wiirzburg,  1875;   Ueber  ])atholog. 

Bindegewebs-  u.  Gefassneubildung,  Wtirzburg,  1876;    Tuberkulo.sc.     Eulenburg's 

Realencyklop.,  xxiv.,  1900  (Lit.),  u.  Eulenb.  Jahrb.,  ii.,  1904. 
J  See  also  §  171. 

§  171.  Tuberculosis  is  at  the  begiiminj?  a  local  disease,  whidi  oocur.s 
most  freqneutly  in  Ihehmgs,  intestinal  tract,  and  skin;  tliat  i.s,  in  ])laces 
accessible  from  witbont.  Cases  of  rri/pfof/niic  in/'cction  are  by  no  means 
rare;  in  these  the  first  demonstrable  (liscase-ciianiics  appear  in  tissues 
concealed  in  the  deeper  portions  of  t  lie  b()(lyi»arciichyma — as,  foi^'xam- 
ple,  in  tlie  lymph-glands,  adrenals,  bones,  joints,  l)rain,  tubes— and  it  is 
to  be  assumed  that  nnder  certain  conditions  the  bacilli  enter  tlie  body 
Avithout  causing  lasting  changes  at  the  point  of  entrance,  so  tliat  tliey 
develop  first  in  some  distant  organ  to  M'hich  tljey  are  carried  1)\- 
tbe  blood  or  lymph,  and  thi-ongh  mnltii>lication  give  rise  to  ti.ssue- 
d?-generation,  to  emigration  of  Avhite  blood-cells,  and  to  proliferation  of 
tissue. 

The  local  disease  nsually  begins  with  1  lie  forniali I"  miliary  tu- 
bercles—that is,  cellular  nodules  of  the  kind  dcsciilicd  :ibov< — -wliich 
arise  in  the  tissue  eithei-  singly  (u-  (in  caseofmuni])le  infection)  in  great 
mimbers  simultaneously,  or  one  after  another  (secondary  dissemination 
of  the  mnltiplying  bacteria).  The  tissue  in  tlie  neighboihood  of  tlu' 
individual  tubercles,  as  well  as  that  between  the  tubercles,  shows  some 
40 


020 


TUK    PATHOGENIC    FISSIOX-FUXGI. 


times  a  more,  sometimes  a  less  pronounced  appearance  of  inllaniniatory 
exudation  and  proliferation  of  an  esi)e('ial]y  ccUnlar  tyi)e ;  and  thronuli 
these  processes  there  are  frequently  foniu'd  large  granulation=areas  in 
the  infected  coimective  tissue. 

In  the  case  of  a  surface  colonizatiun  of  fhr  haciUi,  as  is  i)ossil)le  in  the 
alveoli  of  the  lung  and  in  the  smallest  bronchioles,  an  exudative  catarrhal 
inflammation  may  be  the  first  sign  of  the  infection,  wliih'  ])joliferati\ e 
processes  in  the  connective-tissue  strc^nia  and  in  tlic  ]»nhnonary  vessels 
appear  oidy  at  a  later  period. 

In  the  mucous  membranes  and  in  the  skin  (Fig.  47;>)  large  areas  of 
the  mucosa  and  submucosa,  or  corium  respectively,   may  through  the 


^'»  ^^V.■■^.■^VSv■*V'-'■•'';.■^■''.^■':''- '{'■',  ■■' 


I 


J 


Fig.  473.— Lupus  of  the  skin  with  atypical  growth  of  epithelium,  from  tlie  repion  of  tlie  knee  Calcohol, 
li:einatoxyIin,  fuchsin,  picrie  acifi).  a,  Corium  converted  into  granulation  tissue  in  wliiih  there  are  srat- 
tered  tubercles  ;  /*,  epidermis  ;  c,  epithelial  plufjs  growing  into  the  dt-ppcr  "■ '  *■'       ' '       '  "" 


I's;  (/,  tubercle.     X  ■)(', 


formation  of  such  granuhitions  undergo  a  nodular  or  a  ditfnse  flattened 
thickening.  In  the  serous  membi-anes  there  may  de\  elop  large,  flattened 
nodules  in  whose  neighborhood  the  serosa  is  thickened  and  covered  with 
a  flbrinous  exudate.  lu  the  synovial  membrane  of  the  joints  and  bursas- 
there  often  arise  soft,  spongy  proliferations,  the  so-CA\\ed  fini(/<nis  f/noni-'f^ 
/((tio)is  (Fig.  474)  ;  in  the  periosteum  and  bone-marn)W  round,  grayish- 
red,  or  gray  granulation -areas  of  varying  size  appear.  All  these  areas 
have  one  feature  in  common — namely,  in  their  neighborhood  are  found 
intlammatory  inlilt rations  and  proliferations  of  tissue,  which  bear  the 
cliaiacter  of  a  granulation  tissue  (Fig.  47o,  <( :  474,  b)  inclosing  charac- 
teristic  non- vascular,  cellular  nodules— tubercles  (Figs.  473,  d:  474,') 
— which  often  contain  giant-cells.  In  grayish-red  tissues  rich  in  blood 
the  tubercles  may  often  be  recognized  by  the  naked  eye  as  gray,  or,  whenll 
undergoing  caseation,  as  white  or  y<41owish-white  nodules. 

The  ((rra  of  iuhcrctdou-s  f/rdiiulation  t issue  ^vhen  once  formed  becomesji 
larger  in  its  further  course  of  development  bj'  an  appositiouaJ  groidh,h 


Tl   HKHcn.OSiS. 


62: 


wiu'ichy  tlic  sanu'  procfsst's,  as  jcisl, 
(IcsciilM'd.  coiismninatc  llH-insch  .-s 
at  llic  pciiplH-ix.  'riiciviiiayarisr 
ill  lliis    \\;i\ ,  cilhci-    w  ilhiii    im    jn- 

lacr 

soli- 

as, 


i^f^fe-    - -^i^^^-^^^V^^  t^-'y   tubercles    (Fi-     ^T^,    .) 

fef^;'|;;|iiE--:/i^^..^^^^  ""^"    iiiriv.,u.-iitiy    .vs,.iiii,i..    i 


^^^i^^^v;; 


%iC 


-<.-cj^'f- 


"t«i^-^< 


Fin.  47 4.- Tuberculous  ^anulation  tissue  from 
the  synovial  tni-iiibrane  of  the  knee-joint  (Miiller's 
JIuid,  Jiisiiiunk  brown),  n.  Connective  tissue;  /*, 
granuhitiuu  tissue;  c,  tubercle.     X  80. 


Ilirh 
Inir 
Illinois.  ImiiiIici',  tli*-  lissiic  traii>- 
loniicd  l>y  llic  lulK'iciiloiis  pioc-ss 
or  tlic  newly  loniuMl  lissm-  icsprr- 
tivcly,  may  siiffcr  Aarions  'nio: 
and  tluTc  may  !)«>  dist  in-ni.Nlird 
three  cliii^f  loims  of  termination, 
which  may,  liowevt-r,  Im-  .-ondiined 
in  Aai'ions  ways. 

Ill  a  first"  -ron|.  of  .mv.vs  H,,. 
prodnclioii  of  eoimectixe  lis>ne 
forms  the  most  stiikin-  feature. 
:ind  tliere  results  ;i  connective- 
tissue  induration  of  liie  dise:ised 
tissue  (Fi--.  47<;)  with  the  dexelop 
ment  of  :i  dense.  lil»i'(»ns  eoiiiieet  i\ c 
ti.ssue  (a).  If  the  i)r<ieess  <|.m's  not 
come  lo  a  st:indstill.  ihen"  nia> 
he  lonnd  in  associat  i(ni  with  ilie 
fibrous  tissue  ]n-\\  pio/ih  rulions  of 
f/r(iiii(l(tii()ii  li.s.sKc  {/)),  and  often  also 
a  lar.ucr  or  smaller  iinmher  of  typi- 
(•;d  tiiJtcrcIrs  (V).  |f  the  process 
comes  to  a  c(.niph'te  standstill  :ind 
lo  a  cure  of  the  infection,  the  en 
Tire  area   ma\-  come  to  eonsi-i    ot'  a 


dense  liln-oiis  tissue  (Fig.  477,  <t,  h)  wliich  in  part 
raii;;emeiif  ((/),  ami  in 
l»ait  is  luoi-e  hyaline  and 
lioiuo<;eneons  in  cliar- 
acter.  Jn  tlie  lun<;s  such 
(•onnecti\-e-tissne  nodules 
contain  more  or  less  car- 
bon-pigment (Fig.  477). 

A  second  form  of  ter- 
mination is  a  combina= 
tion  of  caseation  and 
fibrous  induration  com 
I'lising  dense  liluons  lis- 
siie  (  Fig.  478,  h,  (1)  and 
cas<'ous  foci  (a)  of  vary- 
ing si/e. 

Tlie  third  terminaticm 
consists  essentially  in 
caseation,     the    lubeVcu- 


n.xliil 


Kk;.  4;">.-  Lariresiilitarvtulierili'of  I  ,  ihrcen-iM-l- 

luiii  iu  verir<'al  section.    <(.  CerebelUiiii;  .-.   ......  .;.....  i  .i.lherenl  I" 

thf  luhercio;  r.  lauiinated  tubercle;  </.  Kiav  i«ri|ilii'nil  /i>n<' 
aiihennt  to  the  dura  mater  and  beset  witli  yellowlxh-whlte,  nod- 
ular df^josits.    Natural  size. 


028 


THE    PATHOGENIC    FISSION-FUNGI. 


Ions  giaiiulation  tissue  dyiug  and  producing  no  connective  tissue  at  all, 
or  only  in  such  a  slight  amount  that  it  is  completely  overshadowed  by 
the  caseous  masses  (Fig.  479,  c). 

Both   the  fibrocaseous   and   the   purely  caseous   areas  may   become 


rUH. 


*^  ^^^^  ^ 


Fig.  476.— Tuberculous  induration  of  the  lung  (alcohol,  haamatoxylin,  and  eosin).    a,  Eense,  tibrous  tissue; 
/),  cellular  granulation  tissue ;  c,  giant-cells.     X  40. 

fe^^liii^^^  w^-  %;t-^  ■:,-^  -^^v^-  I 


\-..s  M>-  \._,  -  xy^^----;.. 


^^■^^%vg- 


Fig.  477.— Tuberculous  induration  of  the  lung  (alcohol,  haRinatoxylin,  eosin).    a,  Homogeneous  fibrous  ( 
nodules  poor  in  cells  and  in  part  pigmented ;  b,  diffuse  induration  of  the  lung.    X  24. 


TlBKHCl  l.OSIS. 


()•_".) 


healed,  throujih  their  oirdpsidat  ion  from  the  siirroundiuff  lissurs  by  coiinee- 
tive  tissue  (Fiiis.  478,  b;  479,  c,  r).  Siieh  a  healiuj;  can  he  rettaich-d  as 
compk'te  only  when  in  the  connective-tissue  capsule  (  V'x'j;.  479,  r,  r)  ami 


h. 


A^ 


»^ 


I 


Fig.  478.  —Encapsulated  area  of  caseation  of  the  lung  with  induration  and  eruption  of  tul)ercles  in  the 
neighborhood  (formalin,  alcohol,  hematoxylin,  eosin).  a.  Caseous  area;  h,  fibrous  capsule ;  c,  tubercle; 
d,  indurated  lung  tissue ;  e,  area  of  granulation  tissue.    X  40. 


Ji^^^' 


Fig. 
c,  area  ( 
nodules 


•e 

479. -Encapsulated  area  of  tuberculous  caseation  in  the  lung,  n.  Normal  lung  tissue  ;  /.,  pleura ; 
if  caseation ;  r/,  remains  of  elastic  fibres  in  the  area  of  caseation ;  <•.  small  encai>8ulal«'«l  iu.m.'ou8 
;  /,  thickened  pleura.     X  15. 


{;:-!0 


THK    PATHOGENIC    FISSIOX-FUXGI. 


its  iiei.ij:liboi'bood  («)  neither  fresh  gramilatioii -tissue  areas  nor  tubercles 
are  still  present.  Occasionally  calcification  ofthe  encapsulated  caseous 
mass  may  occur  as  a  further  vsign  of  the  termination  of  the  process. 

The  caseous  masses  of  tuberculous  foci  are  sometimes  tirm,  some- 
times soft,  and  in  the  latter  case  very  often  suffer  a  disintegration  and 
liquefaction  leading  to  the  formation  of  milk-white,  crumbling,  and  pul- 
taceous  or  e^•en  thin  fluid  masses,  so  that  the  tuberculous  area  comes  to 
present  the  picture  of  an  abscess  surrounded  by  a  wall  (designated  as 
cold  abscess).     Eupture  and  emptying  of  the  same  externally  leads  to  the 


Fig.  480.— Tuberculous  cavern  in  the  tibia  lalcDhcil,  picric  acitl,  lia-matoxyliu.  caniiiiiei.  Trausverse 
section,  a.  Periosteum  ;  h,  rarefied  cortex ;  c,  periosteal  deposit  of  bone ;  d,  fibrous  tissue  on  the  inner 
surface  of  the  cortex;  e,  granulation  tissue  containing  tubercles;  /,  sequestrum  with  bony  trabecuUi', 
infiltrated  with  granulation  tissue;  jr,  union  of  the  granulation  tissue  with  the  spf|uestrum  ;  Ii.  cavity  that 
had  been  filled  with  pus  and  casedus  masses.     X  3}4, 

formation  of  cavities  or  caverns  and  fistulous  passages  accessible  from 
without,  and,  when  there  is  a  Avide  opening,  to  ulcers. 

Bmntegmtion  and  cavity -formation  occur  particularly  in  tlie  lung,  and 
may  there  lead  to  the  formation  of  cavities  as  large  as  a  man's  fist  or 
larger.  They  also  occur  not  infrequently  in  caseating  lymph-glands,  and 
in  caseous  foci  in  the  kidneys,  brain,  muscles,  skin,  and  bones  (Fig. 
480).  The  cavities  ( // )  contain  in  the  beginning  the  liquefied  tub<M'cu1ons 
tissue,  in  which  not  infrequently  remains  of  the  original  tissue  may  be 
recognized  in  the  form  of  sequestra  (/).  After  the  evacuation  of  the 
contents  the  wall  may  furnish  material  sufficient  to  fill  the  cavity  again 
either  thi-ough  the  secretion  of  pus  or  through  the  breaking-off  of  necro- 
tic tissue.  lUrmorrhaf/cs  not  infrequently  arise  through  the  erosion  of  '■ 
blood-vessels. 

Tlic  iniJIx  (if  fhr  corrnt-s  and  ah.sccsscs  are  usually  lined  by  caseating 
granulation  tissue  containing  tubercles  (Fig.  480,  r') ;  the  surrounding 
tissue  becomes  indurated  in  part,  and  in  i^ait  the  seat  of  caseating  foci. 


Tl   I'.KIJdLOSI; 


r.:n 


Ulcers  occur  most  ireqiU'iitly  in  llit-  iuiummis  nu'inbiaiu'S  (Fiji.   4M,  fi  i 
and  in  the  skin,  siiico  the  snlU'iiiiii:  cascniis  nuisscs  in  tlu'sr  rcjiioiis  most 


y 

/^^-.i... 


;m 


y 

r 

^  ■/  .^ , .. 

,.j 

W 

'-/  c\^- '<^  ^  -  '/J^T^: 


Fig.  4Si.— Tiil)erculous  ulcer  of  the  intent mn  with  eruption 
Bismaix-k  brown),  o,  Mueosii;  h,  .^-ubiimcnsa  ;  r,  niiisciilari> 
/.solitary  foUlele ;  rj,  mucosa  iutiltraii-il  with  cells;  /(,  ulcer; 
tubercle.     :■'.  30. 


>f  tulH-n 

Ics  in  the  ii.-iirhh 

.rh 1 

(aleoh.'l 

inlcriia 

il.  niusculaiis  ext 

crna ; 

',  serosii 

,.  a  It 'a 

if  siifu-nini?:  i.  re 

■cut,  1 

,i'a8e<iu> 

frequently  break  through  to  the  surface.  The  edges  and  l)ase  of  tlie 
ulcers  are  siu-rounded  by  an  inflammatory  zone  of  infiltrated  granulation 
tissue,  often  also  containiug  tubercles. 


."ir.v--,i§; 


M 


Fig.  482.-Beginninff  tuberculosis  of  the  lung  without  catarrli  (alr<.h"l.  onehii.  n.  (•i|.<i.'..us  nr.-a  witn 
remains  of  elastic  tissue;  h.  normal  lunpr  tissue:  c  plMir.i  with  tuherrles  •  /'. ..  iuIhtc  i-s  in  ihe  nHghl^.r- 
hood  of  the  caseous  area:  f.  tubercle  in  the  iileura  :  ./.  periarienal  /..  p.Mlbron.hlal  ..perivenous 
tubercles  of  the  lymph-vessels;  /,•.  new-fnrinatjnii  of  tll.n.u^  usmh-  l)euealh  the  Ihnltinjr  elastic  layer  of  the 
pleura.    X  10. 


(ys2 


THE    PATHOGENIC    FISSION-FUXGI. 


If  a  tuberciilons  focus  does  not  become  healed  thronoh  tissue-iiKln- 
ration,  sequestration  or  encapsulation  of  the  dead  tissue,  or  througli  the 
removal  or  death  of  the  bacilli,  there  exists  the  danger  of  metastasis. 

This  takes  place  first  by  the  lymph-channels;  and  a  part  of  the  pict- 


FiG.  183.— Beginning  tuberculosis  of  the  lung  in  a  two-year-old  cliikl.  Horizontal  section  through  the 
right  lung  (MUller's  fluid,  carmine),  a,  Caseous  area  In  the  region  of  the  anterior  border;  h,  posterior 
inner  border  free  from  tubercles;  c,  transverse  section  of  the  bronchus  ;  d,  t(,,  caseating  lymph-glands ;  e, 
puluir)nary  vein ;  /,  point  where  the  vein  e  has  become  adherent  to  the  lymph-gland  d, ;  cheesy  degenera- 
tion of  the  vein-wall  has  also  begun  at  the  same  point ;  g,  tubercles  in  the  lymph-vessels  of  the  pulmonary 
parenchyma;  h,  periarterial,  i,  peribronchial,  k,  perivenous,  l,  pleural  tubercles;  m,  tubercle  of  lymph- 
vessel  at  hilum  of  the  lung.    X  2M. 


'I  BEHCl  LO.SIS. 


c:i3 


The    lymphogenous    miliary    tuberculosis 
b 


d. 


'&C. 


il-^'^i 


k*f.*F»' 


'•I    ««• 


'^    /5 


mo  of  a  progressive  luberculosis  is  the  (levelopnieiit  of  tuberelcs  in  llio 
lyni])h-spacesand  in  iliewallsof  tlielynipli-vessels  (I'lgs.  4S1,  /,  i^ ;  4si.*,  /•, 
/,  </,  h,  i:  483,  //.  /^  /,  /;,  J,  ni)  in  llie  iieiulihorliood  of  Ilu>  ])riinary  fitciis. 

is  ill  some  cases  liiiiiled 
1<)  llic  iiiiiiiedialc  iicigli- 
horliood  of  llie  |)riin;iry 
I'ocus  (Fig.  4SL»),  at  oilier 
times  it  in\-olves  laigei- 
areas  and  may,  for  ex- 
ample, extend  from  :i 
caseating  tnbei-cle  in  the 
lung  (Fig.  is:],  a  )  (»\('r  a 
l;irg(^  ])art  of  the  pulmo- 
nary lymphatic  system 
(//,  //,  /,  /.-,  /,  ill).  Tiiese 
lymphangoitic  tubercles 
l)resenf  the  ai»])earaiice  of 
bright  gray  nochdes,  often 
sui'ionndedby  a  r<'d  zone, 
and  consist  essentially  of 
the  same  structure  as  the 
primary"  focus. 

The  1 1/  1)1  j>  h  -  fi  1  a  n  <!  .s 
may  be  affected  very  early 
(Fig.  483,  d,  (J,),  where- 
upon tubercles de\elop  in 
them  (Fig.  484,  a,  a  J, 
leading  through  succes- 
sive ciops  of  the  same  to 
a  more  or  less  marked  enlargement  and  finally  to  a  caseation  of  the 
glands  (Fig.  483,  d,  rf,),  or  to  an  induration,  or  to  a  condonation  of  these 
processes.  The  thoracic  duct  may  becojue  infected  fiom  caseating  and 
disintegrating  lymph-glands,  and  through  this  channel  an  infection  of 
the  blood  may  also  take  place. 

Very  often  the  formation  of  metastases  takes  place  also  through 
the  blood=stream  ;  in  the  first  place  by  the  entrance  of  bacilli  thiongh 
the  lymph  from  the  thoracic  duct  as  mentioned  a!»o\ e,  but  \ ciy  (»ften 
also  as  the  result  of  the  direct  entrance  of  haci/li  into  the  circulalin;/  blood. 
In  tuberculous  tissue  the  bacilli  may  pass  dii-ectly  into  small  veins, 
though  the  obstruction  to  the  circulation  due  to  the  dosuie  of  the  vessels 
usually  i)revents  their  further  dissemination.  Often  enough  the  bacilli 
gain  entrance  into  the  larger  veins — as,  for  examjjle,  through  the  adhe.^ion 
of  caseating  lymi)h-glands  at  the  hilum  of  the  lungs  (Fig.  483,  </,)  with 
the  neighboring  veins  ((',/),  the  tuberculous  ]>i<)cess  in\<»lving  tlu^  \ein- 
walls  by  direct  extension.  ]\roreo\er,  an  itifcciion  of  nutnerous  rein.s  with 
tubercle-l)acilli  may  occur  in  the  neighborhood  of  a  tuberculous  focus, 
so  that  the  small  veins  of  an  entire  vascular  system  may  ])resenl  a  well- 
marked  tuberculous  disease — that  is,  an  inllaiumattuy  gianulation-pi-olif- 
eration  of  the  vessel-walls  withthe  foiinationof  tuln'rclesandsubseciuent 
caseation  (Fig.  485,  b),  so  that,  if  t]irond)osis  does  not  occur,  large  num- 
bers of  bacilli  may  enter  the  blood-stream  fi-om  the  diseased  walls.  In 
rare  cases  the  arteries,  particularly  the  i>ulmonai'y  ai-teries,  may  l»econie 
tuberculous  through  infection  from  the  surrounding  tissues,  and  so  may 
give  off  bacilli  to  the  blood-streaia. 


Fig.  484.— Eruption  of  tnl)en'Ies  in  a  Ivinitli-gland  (alcohol, 
haeniatoxylin).  «,  Tubercle;  <(,,  caseous  tubercle  ;  /j,  tissue  of  the 
lymph-grlanU  ;  c,  giant-cell  in  the  centre  of  a  tubercle;  c,,  giant- 
cell  at  the  edge  of  a  caseous  focus  ;  d,  laige-celled  tissue  between 
the  tubercles ;  e,  blood-vessel.    X  150. 


634 


THK    PATHOGENIC    FISSIOX-FUXGI. 


The  transportation  of  the  bacilli  thronoii  the  blood-stream  gives  rise 
to  a  haematogenous  miliary  tuberculosis — that  is,  to  an  eruption  of 
miliarj^  tuliereles  (Fig.  480,  a)  at  those  places  where  the  bacilli  become 
lodged  and  multiply.  Just  where  these  places  will  be,  and  how  numer- 
ous the  tubercles,  depend  upon  the  location  of  the  point  of  rupture  and 
the  number  of  bacilli  entering  the  Wood.  The  entrance  of  many  bacilli 
into  the  blood  may  lead  to  a  general  hannatogenous  miliary  tuberculosis. 

If  the  bacilli  have  entered  the  blood-stream  in  small  numbers  and 
have  been  deposited  in  only  one  organ,  and  if  death  does  not  ensue,  then 
arises  in  this  organ  a  progressive  Jiwmatogenous  local  tuberculosis,  whicli 
runs  a  course  similar  to  that  of  the  primary  focus  coming  from  withoui. 


i^l      'I 


-b 


Fig.4bo.— Tuberculosis  of  tlie  veius  iu  the  ueisrliborhood  of  a  tuberculous  letroperitont-al  lyinpli-jri.n 
(formalin,  taeinatoxylln,  eosln).  a.  Tuberculous  lymph-gland  with  giant-cells  and  caseous  foci;  Ian 
blood-vessels  at  the  periphery;  /),  veins  whose  walls  are  thickened  by  tuberculous  granulation  tissue,  1 1 
inner  layere  of  which  show  caseation  ;  c ,  fat  tissue.     X  2S. 


The  exudative  inflammation  accompanying  the  lymphogenous  and 
haematogenous  eruption  of  tubercles  is  sometimes  moie,  sometimes  less 
proii(tiiiic('(l,  and  is  usuall>  iiiost  severe  in  the  meniugesand  in  the  lungs. 

Hliould  a  tuberculous  focus  in  the  lung  break  into  the  bronchi,  as  the 
result  of  the  softening  of  a  caseous  area,  or  if  acaseating  focus  in  the 
kidney  slionld  inxade  the  lcidney-])elvis,  there  wili  result  a  dissemination 
of  tubercle-bacilli  over  the  surface  of  the  mucous  membranes.  I'loiii 
tlie  )»r(»nciii  the  l)acilli  spread  into  the  tracln-a,  larynx,  iuniitli-eavity, 
and  thence  into  the  alimentary  canal;  through  aspiiation  during  deej) 
<|uick  inspiration,  they  may  l)e  carried  into  otlier  ])ortions  of  the  lungs 
as  yet  unalfected.  From  tiie  kidneys  the  bacilli  may  ]>e  spread  tlirnngli- 
out  the  descending  urinary  passages. 

A  secondary  infection  may  also  result  from  this  spreading  of  the 
bacilli,  yel  diiiy  a.  small  percentage  of  the  bacilli  thus  distributed  give 
j-ise  to  an  inleclit)ii ;  and  experience  has  taught  us  tl'.at  only  Ci-rtain  por- 
tions (»f  the  mucous  membranes  are  susceptible  to  infect  ion — i)articularly 


TrHKIx-ClLOSIS. 


03;) 


the  tonsils  and  the  1\  nipliailcnoid  li 
>viiile  the  (I'sopliatins  and  stomach 
of  the  deseendinii-  nrinaiy  i)assa.<:<' 


«%^ 


ri- 


L'.f  -. 


<»rthc  siii: 
ilninsl    iniii 

'     ki(hlC\     II 

l)lad(lri  are 
whUe  llie  urcll 
remains  nnin\  nh cd. 
If  bacilli  enter 
body=cavities  IIicn 
spread  (»\«'i-  the  snil 
sei<tus  memliranes, 
latter,  an<l  excite  a 
Ihimmation  and  I'o 
nodules  (Fi.u-.   1.S7). 


11  an<l  larjic  inlesf  ines, 
lune;  an<l  in  the  case 
'1\  is,  the  nreters.  and 
ire  nsnalU  infected 
hi 


lost  always 
the    jjreat 


inlect     1 

diffuse    i 

i-matiou 

A  ne\\  -f< 

m 


^^ 


\^ 


Fig.  -ise,— Ha?niatogenous  miliary  tiibeiculosis  of  tlie 
lirer  (alcohol,  carmine),  a.  Developed  tubercle  in  the 
connective  tissue  about  tlie  portal  vein  ;  h,  collection  of 
leucocytes.    X  1511. 


issociatcMJ  A\  ith  tliat  caused 


/ 


mat  ion  ol  connect  nc  t  issu 
follow   later. 

Slioiihl  tiiLeivle-hacilli  l>e 
present  in  the  circnlat  iii.u  blood 
of  a  woman  (hiring-  preiinancy, 
the  infection  of  the  placenta 
and  f(ttus  may  follow,  so  lliat 
the  child  will  "he  horn  alieady 
infected.  In  so  far  as  data  con- 
ceiniiii;'  this  ]»oint  exist,  this 
event  is  not  of  frequent  occur- 
rence; and  it  is  more  usual  for 

children  of  iithcrculou!^  ^ntnni.s  to  Ixcoine   iiifrrfrd  after  hirth.     A  coucep- 

tional  infection  of  the  eml)ryo  through  infected  semen  has  not  yet  been 

demonstrated,  and  is  very  unlikely. 

Secondary  infections  are  not  infie(pientl> 

by    luberch'- bacilli,     and 

this    occnrs    particularly 

when   the  disintegration- 

cavities  or  iilcei\s  are  ac- 
cessible     from     Avithout. 

SiTondanj  infcctlom  of  tn-  ^      '■ 

h/'rriiJoKslioif/.'i  are  of  Acry 

frequent  occurrence,  and  ^^, 

are    due    particularly    to        ^-f 

drcptocoeci  "and    staphylo- 

cocci,   pnenmococcij    influ- 

cnza-haciUi,    micrococcus 

irtrof/ctnis,    and    hartrriuiii 

voU.     ]Many   authors    are 

iiicline<l  to  refer  all  severe 

intlammatory    exudations 

accompanying  pulmonary 

tuberculosis  to  such  secon- 
dary infections;  but    this 

is    not    correct  in  so  far 

that  tlu^  formation  of  tu- 

bei-cles  by  tubercle-ba(;illi 

may  be  accompanied    by        j,,,^   ^87.Tubercuiosis  o„,e.ai  <Mi.:ier-s 

inflammatory    exudations     centre  ..f  tubenie:  /<,  ceiis  of  epiiiieii..i.i 

„,.  1  •  .,  -I      J.        phatic  elements;   (/,  prollfenitinir   epiilieliiin 

ol     such     seventy     that      Ihe  neii:i!i".iiioo.i.    x  -^y 


^'  || 


^ 
■# 


riiilne).  (I, 
;  c,  lyni- 
leliuiio  in 


636  THE    PATHOGENIC    FISSIOX-FUNGI. 

serous  or  serofibrinous,  or  pure  fibrinous  or  fibriuopurulent  exudates 
may  collect  in  larue  quantities  in  the  tissues  (in  the  i)ulnionary  alveoli, 
on  the  pleura,  and  in  the  subarachnoideal  space,  etc.  ).  A  high  (septic) 
fever,  rapid  destruction  of  tissues  with  a  tendency  to  suppuration,  and 
an  unusually  severe  inflammation,  in  part  of  a  hsemorrhagic  character, 
point  to  a  secondary  infection.  Nevertheless,  it  is  often  impossible  to 
determine,  without  a  special  investigation  directed  to  this  i^oint,  whether 
a  pure  tuberculosis  or  a  mixed  infection  is  present. 

For  the  treatment  of  tuberculosis  with  bacterial  extracts  and  curative 
serum  see  g  32. 

Tlie  question  as  to  how  often  tuberculosis  is  transmitted  by  the  passage  of 
bacilli  from  the  mother  to  the  child  is  still  an  open  one.  It  has,  however,  been 
shown  by  S'huioH,  Birrh-llirsrhfilil,  and  Landauzy  th&t  in  cases  of  miliary  tuberculosis 
in  pregnant  women,  tubercle  l)acilli  are  present  both  in  the  intervillous  spaces  and  in 
the  blood  of  the  chorionic  vessels,  and  that  the  liver  of  the  foetus  may  contain  bacilli. 
Further,  cases  of  tuberculosis  of  the  placenta  aiso  occur  (Sclimorl,  lu/ckel,  Limgiritz, 
Wfirthin  and  Cmcie).  which  may  be  regarded  as  stages  on  the  way  of  the  tubercle- 
bacillus  from  the  mother  to  the  fetus. 

Cases  of  tuberculosis  occurring  at  an  earlj^  period  of  life,  reported  by  Demme, 
Banmgnrten,  Rilliet,  Clcarrin,  and  others,  as  well  as  the  statements  of  Armdnni,  Lmi- 
douzy,  and  Martin,  that  the  inoculation  of  portions  of  the  organs  of  human  fo?tuses 
obtained  from  tuberculous  mothers  produced  tuberculosis  in  guinea-pigs,  speak  in  favor 
of  a  passage  of  tubercle-bacilli  from  the  mother  to  the  foetus.  Still  more  important  are 
the  experimental  investigations  of  de  Benzl  and  Gartner,  who  succeeded  through  the  in- 
oculation of  pregnant  guinea-pigs,  white  mice,  and  rabbits  in  producing  tuberculosis  in 
a  part  of  the  young  born  of  these  animals.  Gartner  is  consequently  of  the  opinion  that 
under  certain  conditions  tubercle-bacilli  may  pass  from  the  mother  to  the  fo?tus  in  the 
case  of  both  animals  and  man.  Finally,  Maffucci  and  Baiinu/arten  succeeded  in  effecting 
a  transfer  of  tubercle-liacilli  to  impregnated  hen's  eggs,  and  discovered  that  the  infec- 
tion did  not  disturb  the  development  of  the  chick,  but,  on  the  contrary,  the  bacilli  that 
were  taken  np  by  the  embryo  remained  in  the  tissue  of  the  latter  without  multiplying 
to  any  extent,  later  to  cause  a  tuberculosis  in  the  body  of  the  hatched-out  chick.  Ac- 
cording to  the  evidence  of  anatomical  investigations  a  placental  trein amission  of  tuber- 
culosis to  the  child  cannot  be  doubted.  On  the  other  hand,  a  conceptional  transmission 
of  tuberculosis  from  the  father  to  the  embryo  has  not  yet  been  proved.  Moreover,  ac- 
cording to  th^  investigations  made  up  to  the  present  time  it  may  be  emphasized  that 
tuberriilnfiis  is  to  hr  rrfcrred  iisiinlly  to  an  extrauterine  infection  and  tliat  children  of 
tuberriilniis  jHin  iitfi  sulVcr  from  tuberculosis  so  frequently  because  they  are  more  exposed 
to  (III  iiifirt!<ni  icitli  /'/V/v'/Ay.s/.<<  than  are  the  children  of  healthy  parents.  An  especial 
prtilisiinxiti'n,  to  tuberculosis  in  the  children  of  tuberculous  jMrents  has  not  jet  been 
demonstrated. 

In  aiiiiiials  a  transmission  of  tuberculosis  to  the  foetus  seems  occasionally  to  occur, 
according  to  the  reports  of  Zippelius,  Jessen,  Pi'itz,  Grothans,  Malvoz,  Lydtin,  Brourier, 
Adams,  and  others.  Johne  was  not  only  able  to  demonstrate  in  a  f(etal  calf  the  pres- 
ence of  miliary  nodes  and  larger  nodules  in  the  lungs,  liver,  and  various  lymph-glands, 
but  also  to  show  the  presence  of  characteristic  bacilli  in  the  hsions. 

From  the  side  of  clinicians  and  physicians  the  so-called  scrofula  has  been  many 
times  regarded  as  an  especial  pathological  condition  of  the  organism  of  the  child,  pre- 
disposing it  in  an  especial  degree  to  tuberculosis.  As  scrofulous  are  regarded  those 
children  who  permanently  or  at  least  very  frequently  suffer  from  inflammations  of  the 
mucous  membranes  (nose  and  its  accessory  cavities,  conjunctiva,  middle  ear),  as  well  as 
of  the  skin,  also  from  swelling  of  the  lymph-glands  leading  occasionally  to  necrosis  and 
suppuration,  Anally  also  from  chronic  inflammations  of  the  bones  and  joints,  and  who 
present  a  flabby,  pale,  often  bloated  appearance.  In  many  cases  these  symptoms  are 
due  to  tuberculosis;  in  other  cases  they  are  caused  by  an  infection  with  streptococci  or 
staphylococci,  or  are  the  results  of  syphilis.  Scrofula  is  not  a  disease-entity,  but  is  only 
an  especial  sj'mptom-comple.v  belonging  to  different  diseases.  Whether  the  affected 
children  possess  an  especial  predisposition  to  all  these  injections  which  may  be  designated 
as  scrofula  is  difficult  of  proof.  The  organism  of  the  child  is  in  general  easily  infected 
by  these  agents,  and  the  fretpient  illness  of  certain  children  due  to  these  infections  may 
be  referred  to  a  lack  of  cleanliness,  or  to  especial  conditions  of  the  environment  of  the 
child,  or  to  frequent  injuries,  etc.,  as  well  as  to  an  especial  predisposition  of  the  child 
itself. 


. 


TIBEHCULOSIS. 


637 


)'on  Bchring  has  in  recent  years  upheld  (lie  view  tliat  tubercnlosis  is  nhnost  al- 
ways the  result  ot  bacilli  enteriui;  throui^h  the  intestine  in  infancy,  and  that  later 
infections  play  a  wholly  subordinate  role.  This  tiieory  is  correct  in  .so  far  as  tlie  lonjj- 
known  fact  is  concerneil,  that  the  intestine  of  infant.s'*akes  up  the  bacilli  more  easily 
than  the  adult  intestine,  ami  that  the  infection  is  not  always  manifest  at  tiie  point 
through  which  the  bacillus  enters,  but  develops  first  in  those  organs,  the  lymph-nodes, 
lungs,  brain,  bones,  etc..  to  which  it  has  been  carried  by  the  i)lood  or  lymph.  Infec- 
tion with  tubercle-bacilli  may  occur  at  any  age.  Furtlier,  the  i^rimary  intestinal  in- 
fection is  not  the  dominating  one,  but  the  infection  of  the  respiratory  tract  is.  Tiie 
latter  results  usually  from  the  direct  entrance  of  the  bacilli  into  the  resjiiratory  jiaren- 
chyma.  Primary  infection  of  the  nose,  larynx,  trachea,  and  bronchi  al.so  occurs,  but 
is  relatively  much  le.ss  frequent  than  the  jirimary  lung-alTection. 

Calmette's  view  of  the  intestinal  o"gan  of  anthracosis  lias  al.so  been  turned  as  an 
argument  favoring  the  ingestion-theory  of  tuberculosis.  Much  has  been  written  upon 
this  subject  tluring  the  last  several  years,  and  while  tlie  ojiinion  of  tlie  majority  of 
jiathologists  favors  the  aerogenous  nature  of  tulierculous  infection  in  late  ciiildliootl 
and  in  adult  life,  the  etiological  importance  of  infection  tlu-ough  tiie  intestine  in  infancy 
has  been  increased  to  such  an  extent  that  this  mode  of  infection  cannot  lie  disreganic.l 
l)ractically. 

Tuberculosis  of  mammals  isob.served  most  frequently  in  tlie  case  of  mltlr.  .-iiid 
]iresents  in  general  a  course  similar  to  tliat  of  the  disease  in  man.  thougli  the  g-unula- 
t  ion-areas  develop  more  frequent- 
ly into  larger  tumor-like  nodules, 
]iarticularly  so  in  cattle,  and  the 
tendency  to  a  generalization  of 
the  disease  is  le.ss.  The  tuber- 
culosis of  the  serous  membranes 
wliich  is  often  designated  as  pearl 
disease  {"Perlsucht  ")  begins 
with  the  formation  of  small  nod- 
ules, leading  then  to  a  more 
marked  proliferation  of  the  con- 
nective tissue,  giving  rise  to  the 
formation  in  the  thickened  serosa 
of  nodules  of  the  size  of  a  jjea  or 
bean  or  even  as  large  as  a  hen's 
egg  or  man's  fist  (Fig.  488), 
which  in  the  beginning  are  soft 
and  sarcoma-like,  but  later  be- 
come firmer  and  denser  and  often 
enclose  calcified  areas  of  casea- 
tion. The  form  of  the  prolifera- 
tion is  sometimes  villous-like  and 
warty,  at  other  times  of  a  mul- 
berry- or  grape-like  form,  cauli- 
fiower-like  or  even  polypoid. 

Next  to  cattle  the  hog  is 
most  freciuently  affected  with 
tuberculo.si.s,  more  rarely  the  hor.se,  goat,  .sheep  and  cat,  and  still  more  rarely  the  dog. 

Of  wild  animals  in  captivity,  the  ape,  lion,  tiger,  bear,  jackal,  panliier,  jaguar, 
giraffe,  and  dromedary  ea.sily  accjuire  tuberculosis.  Of  the  small  anim;ds  used  for 
experiment  the  guinea-pig  is  the  most  suscejjtible.  After  sul)cutaneous  inoculations 
there  results  a  progre.s.sive  tuberculosis  which  kills  the  animal  in  from  alxiut  four  to 
eleven  weeks.  In  rabbits  an  inoculation  tul)erculosis  may  iical.  Field  mice  and  white 
mice  are  infected  with  difficulty. 

Tuberculosis  is  of  frequent  occurrence  in  birds  (chickens,  pigeons,  pheasants,  and 
parrots),  and  is  usually  localized  in  the  ulxlominal  organs. 

The  cultures  of  tubercle-bacilli  from  man  are  dry,  warty,  or  .scaly  and  lustrele.s.s; 
those  of  avian  tuberculosis  moist,  wrinkled,  and  .soft,  and  moreover  grow  l)est  at  43°  C, 
Dogs  are  wholly  immune  to  avian  tuberculo.sis,  but  not  to  human  tul)erculosis.  The 
intraperitoneal  inoculation  of  mammalian  tuberculosis  {Leray)  cau.ses  in  rabl)its  numer- 
ous caseous  foci  in  the  liver  and  .spleen  witii  few  giant-cells  and  scanty  l)acini.  and  in 
the  lungs  numerous  caseous  nodules  containing  mimerous  bacilli.  Inoculations  mto 
these  animals  of  chicken-tuberculosis,  on  tlie  other  iiaiid.  cause  a  .scanty  production  (.1 
non-caseating  cellular  proliferations  cont.nining  giant-cells  and  great  numl)ers  of  l)acilli. 

According  to  Mafjucci,  Martin,  (lartner,  and  others,  the  inoculation  of  liuman 
tuberculosis  into  chickens  does  not  produce  tuberculosis,  but  the  bacilli  remain   alive 


]  i(.    4H,S.— (.n)\Mlwfii 


638  THE    PATIIOGEXIC    FI.SSIOX-FUNGI. 

for  weeks  within  the  Ijody  oi  the  chicken.  Pigeons  {Auclair)  die  after  intraperitoneal 
inoculation,  bu.  no  tubercles  are  found  in  tiie  tissues;  the  liver  and  lungs  may  con- 
tain livirg  bacilli  fourteen  days  after  the  inoculation.  In  guinea-pigs  (Straus)  the 
bacilli  of  human  tuberculosis  cause  much  more  severe  changes  than  do  the  bacilli  of 
chicken-tuberculosis.  In  mice  infected  with  avian  tuberculosis  (Weber  and  Bnfin^r) 
there  occurs  a  moderate  increase  of  the  bacilli  without  intoxication  and  without  any 
marked  reaction  on  the  part  of  the  tissue.  When  kept  in  the  mammalian  body 
(guinea-pigs  and  mice)  for  one  to  two  years  the  virulence  of  avian  bacilli  for  guinea- 
pigs  is  not  changed.  Whether  man  is  susceptible  to  avian  tuberculosis  is  still  an  open 
question. 

The  question  whether  the  tuberculosis  of  animals,  particularly  of  the 
domestic  animals,  is  identical  with  that  of  man  has  been  the  subject  of  lively  dis- 
cussion during  recent  years.  The  majority  of  writers  believe  in  their  identity.  Koch 
and  vo)i  Baumgurten  deny  it.  In  favor  of  the  latter  view  may  be  taken  the  fact  tliat 
the  bacilli  of  different  sources  show  differences  in  cultures,  cultures  of  avian  tuber- 
culosis in  particular  showing  essential  differences  from  those  of  human  tuberculosis. 
Further,  inoculations  of  human  tubercle-bacilli  into  domestic  animals,  for  example, 
into  cattle,  are  either  negative  or  cause  a  milder  disease  than  that  resulting  from  the 
inoculation  of  bacilli  obtained  from  sick  cattle.  In  spite  of  these  facts  it  cannot  be 
doubted  that  we  have  to  deal,  not  with  different  forms  of  disease;  but  that  the  tuber- 
culosis of  man  and  that  of  the  domestic  animals  are  identical  diseases  produced  by 
varieties  of  the  same  species  of  bacillus.  When  the  bacilli  increase  for  a  long 
time  within  the  same  species  of  animal  they  acquire  properties  that  make  them  less 
virulent  for  other  species  and  they  are  Wich  difficulty  made  to  grow  in  the  latter. 
Human  tuberculosis  is  nevertheless  still  directly  transmissible  into  other  mammals, 
and  man  may  be  infected  with  the  bacilli  of  mammalian  tuberculosis.  Uncooked 
cow's  milk  and  meat  containing  tubercle-bacilli  can  convey  bovine  tuberculosis  into 
man,  and  the  attendants  of  cattle  can  be  infected  from  sick  animals  also  through 
ujunds  or  the  respiratory  tract.  The  avian  strain  of  tubercle-bacilli  is  the  farthest 
removed  in  its  properties  from  the  human  strain.  In  parrots  there  occurs  also  a 
tuberculosis  the  bacilli  of  which  are  identical  in  their  propertie:;  with  those  of  the 
bacilli  of  human  tu])erculosis. 

Tuberculosis  occurs  also  in  cold=blooded  animals,  fish,  blind  worms,  frogs, 
snakes,  lizards,  tortoises,  etc.,  and  is  likewise  caused  by  an  acid-fast  bacillus,  that  pos- 
sesses an  optimum  of  growth  at  15°  C,  and  grows  at  temperatures  of  10°-31°  C.  It 
has  been  assumed  (Bataillon,  Ferre,  and  others)  that  this  bacillus  is  also  a  variety  of 
the  bacillus  of  mammalian  tuberculosis.  Friedmunn  has  attempted  to  inuiiunize 
guinea-pigs  against  tuberculosis  by  inoculating  them  \\\i\\  the  less  virulent  !)aci]li  of 
the  tuberculosis  of  cold-blooded  animals. 

As  pseudotuberculosis  may  be  classed  all  those  affections  characterized  by  the 
formation  of  cellular  and  fibrous  nodules,  and  in  part  also  imdergoing  neci-osis,  and 
which  are  similar  to  tubercles,  but  which  are  not  caused  by  Koch's  bacillus.  Accord- 
ing to  the  etiology  the  following  forms  may  be  distinguished: 

1.  Pseudotuberculosis  due  to  dead  foreign  bodies.  This  may  be  caused  by  the  experi- 
mental injection  of  lycopodium-spores,  olive-oil,  and  mercury  into  the  blood-vessels, 
the  inhalation  of  irritating  material  into  the  hmgs,  the  injection  of  large  quantities  of 
milk  into  the  peritoneal  cavity,  etc.  The  piesence  in  tiie  tissue  of  caterpillar  hairs, 
pieces  of  wadding,  silk  threads,  etc. ,  cholesterin  table 
and  stomach-contents  wiiicli  liave  gained  entrance  iiUo 
also  lead  to  the  formation  of  tihroeelliilar  nochdes. 

3.  IM'mhdulM'iruIosiH  raiisvd  bi/  inonmnorphoux  andy* 
IhirhnI--:.  and  Hexner  h-.ive  described  forms  of  Chi,h,ihri 
a]>|iaiently  tuberculous  lungs  and  bronchial  glands  wli 
as  1  ill' cause  of  the  disease.      ConruiDid  UmwA.  in  an 
a  bacillus  wiiicli  was  not  identical  with  yv'w//'.s  baciil 

resemi)liiig  tuberculosis  may  lie  jji-oduced  in  guinea-pigs  by  the  injection  of  the  buttci- 
bacillus  ol  Itnbuto/ritsch  (which  probably  comes  from  cow-dung)  as  well  as  by  tiie  grass 
l)acillus  of  Moeller;  and  in  white  mice  by  the  inf)culatioii  of  tiic  butter-baciliusof  A'"//'. 

In  the  rodents  a  disease  resembling  tuberculosis  is  not  infre<juently  produced  liy  a 
plump,  thick  bacillus  witli  rounded  ends  (Pfciffcr,  Pirinz.  Zanm-i,  ^\»rii'rd,  B(»i»)nc,  bd- 
banco.  and  others).  Other  forms  of  bacillary  pseudotuberculosis  liave  lieen  observed  in 
rabbits  (Ebcrth),  in  birds  (Mnir),  in  tiie  cow  (Vourinoiit),  etc. 

8.  Pxeudi>tnberculoHiH  due  fo  /ti/jJionn/fctcs  occurs  in  the  hmgs  and  may  be  produced 
artificially  liy  the  injection  of  difl'erent  forms  of  aspergillus  and  mucor;"but  tJie  affec- 
tions so  produced  show  peculiarities  wlii(;li  make  possible  a  differentiation  from  true 
tuberculosis. 

4.  I's(iid,,tiibi'rriilnsis  caused  hi/ anunal  jjarasttcs  occurs  ].ar1  iculariy  in    the  sheep, 


*sfi 

om  rupturei 

I  ov 

aiian  cysls, 

the 

periK 

meal  c; 

ivit\ 

•,  etc.,  may 

ili/n 

(iriihi) 

/,s  hirt, 

rii(. 

Fjipi/it/cr, 

/■'and  Sin 

ptothri 

r  oh 

aiiieil  from 

lieh 

they 

are  in( 

liii. 

I  to  reganl 

larc 

itly  tubercul 

ous 

'Ibow-joiiit 

Ai 

atl'ec 

tion  of  thv. 

peritoneum 

TriJKlUTLOSlS.  (•).•{'.) 

liog,  goat,  cut.  hare,  roe,  stag,  and  ohainois,  and  it  is  caused  l»y  dilTerent  fmnis  oi.Stioii- 
fiyliix  and  by  PKi'iidaliiis  copi/lfirig  (M//U<r):  it  is  tlierclore  a  vciinian  psoidctttdjcroidosis. 

Literature. 

(P<(tJi()/<>f/i/  <>/  Tiihtn-iilo.si.s.  ) 

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1SS;>;    Experimentelle  congen.  Tnberkulose.     Arb.  a.  d.  patli.  Inst,  /u    rubiMirtii, 

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I 


fi40  THE    PATHOGENIC    FISSION-FUNGI. 

Romberg:   Die  Serumdiagnose  bei  Tuberkulose.     D.  med.  Woch.,  1901. 

Sawada:   Hiimatogene  Miliartuberkulose    der  Lunge.      I).  A.   f.  klin.  Med.,  76  Bd., 

l(H);i. 
Sanchez  Toledo:    Transmission  de  la  tubercul.  de  la  mere  au  foetus.     Arch,  de  med. 

exp..  i.,  1889. 
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SuD])!.,  1899. 
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Schliiter:    Die  fotale  tuberkulose  Infektion,  Leipzig,  1902. 
Scliinorl  u.  Birch-Hirschfeld:  Uebergang  von    Tuberkelbacillen  aus  dem  mtitter- 

hclien  Bhit  auf  die  Trucht.     Beitr.  v.  Ziegler,  ix.,  1891. 
Schmorl  u.  Geipel:    Tuberkulose  der  Placenta.     Verh.  d.  D.  path.  Ges.,  vii.,  1904. 
Schmorl  u.  Kockel:    Tuberkulose  der  menschl.    Placenta.      Beitr.  v.  Ziegler,  xvi., 

1S<»4. 
Schottlander:  Ueber  Eierstockstuberkulose,  Jena,  1897. 
Schlirhoff:     Pathogenese  der  allgem.    Miliartuberkulose.       Cbl.   f.   allg.    Path.,    iv., 

1893. 
Straus:    La  tuberculose  et  son  bacille,  Paris,  1895. 
Virchow:    Die  krankhaften  Geschwiilste,  ii.,  Berlin,  1865. 
Warthin:  Tuberculosis  of  the  Placenta.     Jour,  of  Infect.  Dis.,  1907. 
Weig-ert:    Die  Entstehung  d.  acuten  Miliartuberkulose.     Deut.  med.  Woch.,  1897. 
Wild:    Entstehung  der  Miliartuberkulose.     Virch.  Arch.,  149  Bd.,  1897. 
Ziegler:   Ueber  Tuberkulose  u.  Schvvindsucht.     Samm.  klin.  Vortr.  v.  Volkmann,  No. 

151,  1878;  Tuberkulose.     Eulenburg's  Realencyklop.,  xxiv.,  1900  (Lit.),  u.  Eulen- 

burg  Jahrb.,  1904. 

See  also  §  170. 

(Tiibe)Ti(Iosis  of  Animals.      PseudoiiihcrcHlosh.) 

Apostopulos:    Histologic  d.  Pseudotuberkulose.     Arb.  her.  v.  Baumgarten,  ii.,  1896. 

Auclair:    La  tub.  humaine  chez  le  pigeon.     Arch,  de  med.  exp.,  1897. 

Bang:   I']utertuberkulose   u.  tuberkulose    Milch.      Deut.    Zeitschr.   f.  Thiermed.,  xi., 

1SS5. 
Baumgarten:    Uebertragung  d.  Tuberkulose  durch  die  Xahrung.     Cbl.  f.  klin.  Med., 

ISSl. 
Bollinger:    Identitat  d.  Perlsucht  mit  menschl.  Tuberkulose.     Miinch.  med.  Woch., 

1X95. 
Bonome:  Sulla  pscudotuberculosi  microbica.     Arch,  per  le  Sc.  Med.,  xxi.,  1897  (Lit.). 
Chantemesse:    La  tubercuiose  zoogleique.     Ann.  de  ITnst.  Pasteur,  1887. 
Courmont:    Tuberc.  bacillaire  d'origine  bovine.     Et.  sur  la  tub.  publ.  par  Verneuil, 

ii.,  1890. 
Delbanco:    Pseudotuberkulose  d.  Nagethiere.     Beitr.  v.  Ziegler,  xx.,  1896  (Lit.). 
Eberth:    Pseudotuberkulose  d.  Kaninchens.     Fortschr.  d.  Med.,  1885;    Virch.  Arch., 

1()_'  Bd..  1885. 
Frothingham:    Impfversuche  an  Kalbern.     Zeitschr.  f.  Thiermed.,  i.,  Jena,  1897. 
Gilbert  et  Roger:    Inocul.  de  la  tuberculose  aviaire  au  cobave.     Mem.  de  la  Soc.  de 

biol.,  1S9]. 
Grancher  et  Ledoux-Lebard:    Tuberculose  zoogleique.     Arch,  de  med.   exp.,  1889, 

1S9(). 
Jeanmaire:   Hist.  Verand.  bei  d.  verminosen  Pneumonie  d.  Katzen  u.Hasen.     Inaug.- 

Diss.,  Freiburg,  1900. 
Jensen:    Tuberkulose  beim  Hund  und  bei  der  Katze.     Deut.  Zeitsch.  f.  Thiermed., 

xvii.,  1891. 
Joline:    Die  Geschichte  der  Tuberkulose,  Leipzig,  1893;    Huhnertuberkulose.     Deut. 

Zeitschr.  f.  Thiermed.,  x.;    Uebertragung  der  Tuberkulose  v.  Mensch  auf  Hund. 

lb.,  xiv.,  1889. 
Kastner:   Infectiositiit  des  Fleisches  perlsiichtiger  Thiere.     Miinch.  med.  Woch.,  1892. 
Kostenitsch  et  Wolkow:    Tuberculose  aviaire  chez  le  lapin.     Arch,  de  med.  exp., 

.,  1S93. 
Kruse:   lliihnertuberkvilose  beim  Menschen  u.  Siiugethier.     Beitr.  v.  Ziegler,  xii.,  1893. 
Leray:    Tub.  ae  I'homme  et  tub.  aviaire.     Arch,  de  med.  e.xp.,  vii.,  1895. 
Mafifucci:  Aetiologie  a.  lub.     Cbt.  f.  a.  Path.,  i.,  1890;    Hiihnertuberkulose.     Zeitsch. 

I.  lij'g.,  xi.,  1892. 
Malassez  et  "Vignal.    Tuberculose  zoogleique.     Arch,  de  phys.,  iv.,  1889. 
Muir:    On  Pseudotuberculosis.     Journ.  ot  Path.,  v.,  1898. 

Miiller.   Die  Nematoden  a.  Saugethieriungen.     Deut.  Zeitschr.  t.  Thiermed.,  iv.,  1889. 
Ostertag:    Handbuch  der  Fleischbeschau,  Stuttgart,  1904. 


SYriiiLis.  G41 

Pfeifier:    T'oher  die  bacilliirc  P.stMKlotulKTkuldse  bci  Nagctliiercn,  Lvip/At^,  ISSS. 
Ribbert:    Vcrbreitunsi  (lt>r  Hiu-illen  bi'i  lliilinorn.     Dcut.  mod.  Woeli.,  bss;{. 
Straus  vt  Gamele'ia:    Hocli.  cxii.  sur  la  tubcrciilosc.     Arcli.  dc  nu'd.  v\\t..  iii..   ISOl. 
Weber  u.  Bofinger;    Hiilni(Mtul.(Tkul..sc.      luli.  Arb.  a.  d.   I\.   ( ;csiiiidlicits:iiiitc,   i., 

lltl)4. 
Wehmer:  Pcrlsucht.     ]>uloiil)urn'.s  Koak-iu-vklop..  xviii.,  bS9S  (Lit.). 
Wolfie:    IVrlsufht  u.  iiKMi^flik  'i'liherkiilost-. "   I),  nu'd.  Woch..  lOOL'. 
Wrede:    rstMukitiiborkuloseliaciUeu  bt'iiu  .Mensclu-n.      ]^.  v.  Z.,  xxxii.,  19().'5. 
Zagari:    Tuberculosis  zoofjloeioa   oikn-   rseudotiiberkuiose.     I'ortschr.   ik    .Med.    vii., 

1  Situ. 
Ziegler:  Tiiberkuk)se.     luik'iiburii's    KeakMicvkk)p..   \\i\..     litdO     (Lil.).    ii.    Jaik'ii. 

Jahrb..  ii.,  19()k 

?;172.  Syphilis  is,  like  tubt'i'culosi.s,  an  iiilVctidUs  di.sfa.H',  whicli, 
]ii<te«'odiiig- from  a  local  infection,  spreads  throniiiiont  tlic  oijianism  by 
Hicans  of  the  blood- and  lyinpli-clianncks,  and  leads  to  the  foiination  of 
localized  intiammations  and  i)r(>liferations  of  j;rannIation  tissne,  vhicli, 
however,  do  not  present  so  cliaracteristic  a  structure  as  does  the  tnl)ercle. 

In  1905  Schaudinyi  and  Hoffman  announced  the  constant  occurrence  in  .syphilitic 
lesions  of  a  characteristic  organism.  Control  examinations  of  nnn-sypiiilitic  lesions 
failed  to  reveal  it.  To  the  newly  discovered  parasite  the  name  of  Spirochtete  pal- 
lida was  given.  Corroboration  of  the  finding  of  Schaiulinn  and  Hoffman  was  .soon 
forthcoming  from  a  large  number  of  investigators  in  all  parts  of  the  world,  it  was 
found  to  ))e  constantly  piresent  in  the  primary  lesions,  in  all  forms  of  secondary  and 
tertiary  lesions,  in  the  blood,  lymph,  and  cerebrospinal  fluid  of  syphilitics,  in  the 
lesions  of  congenital  syphilis  and  in  the  blood,  lymph,  cerebrospinal  fluid  and  organs 
of  ca.ses  of  congenital  syphilis,  and  in  the  placenta  of  such  cases.  It  has  also  been 
demonstrated  in  the  experimental  syphihs  of  apes  {Metschnikoff).  But  little  evidence 
has  been  brought  again.st  its  position  as  the  etiological  agent  of  .syi)liilis,  and  the  ma- 
jority of  writers  now  accept  it  as  such.  Control  investigations  have  been  particularly 
unanimous  as  to  its  absence  in  non-syphilitic  lesions.  Although  the  organism  has  not 
been  cultivated  and  the  third  and  fourth  laws  of  Koch  have  not  yet  been  fulfilled,  we 
are  justified  from  the  evidence  now  at  hand  in  considering  the  presence  of  the  Spiro- 
chete pallida  as  diagnostic  of  syphilis,  even  if  we  cannot  shoiv  positively  that  it  is  the 
causal  agent. 

The  Spirochete  pallida  is  a  delicate,  non-refractilc  sj^iral  organism,  varying  in 
length  from  2-20  /£,  the  average  length  being  about  4-14  //.  The  spirals  are  tight 
and  corkscrewlike,  fading  out  at  the  pointed  ends.  They  vary  in  munber  from  threi- 
to  twenty-five  or  more.  The  large  nimiber  of  spirals  in  proportion  to  the  length  of 
the  entire  organism  is  very  characteristic.  The  whole  organism  is  usually  somewhat 
curved.  Delicate  terminal  flagella  have  been  observed.  The  spiral  form  is  retained 
when  the  organism  is  at  rest.  It  has  the  power  of  rotation  on  its  long  axis,  of  moving 
forward  and  backward,  and  of  making  whip-like  undulations.  A  nucleus  has  not  been 
positively  demonstrated.  It  does  not  bear  spores  and  no  evidence  of  transverse 
division  has  been  observed.  «Sc/iau<iinn  believed  that  it  luwsc.sses  an  undulating  mem- 
brane. At  the  present  time  it  is  not  definitely  decided  whether  to  regard  tiie  organ- 
ism as  a  protozoon  or  as  a  spirillum.  Schandinn  favored  the  former  view.  In  accord- 
ance with  this  belief  the  names  Spironema  and  Treponema  pallidum  liave  l)een  proposed 
for  it. 

The  Spirochcete  pallida  stains  very  poorly,  but  can  be  easily  dem()nstrat<'d  in 
smears  from  primary  lesions  by  staining  with  Wright's  stain,  tiie  Uomanowsky  or  tiie 
Giemsa  stain.  It  is  very  inijHJrtant  that  the  smears  be  stained  as  soon  as  made:  it 
often  cannot  be  found  in  smears  that  arc  not  jierfectly  fresli.  From  tlie  Siiinxhatv 
refringens  it  is  distinguished  by  its  delicacy,  pale  staining,  and  the  mimber  of  its 
spirals  and  their  tight,  corkscrew  arrangement.  The  refringens  is  larger,  thicker,  more 
refractile,  stains  easily,  and  has  broad,  loose  wavy  spirals,  and  its  ends  arc  usually 
blunt.  Levaditi's  method  may  be  used  for  staining  the  ])allida  in  sections.  For  liter- 
ature concerning  Sp.  pallida  see  Folia  Hwrnatologica,  190.3,  190(1.  1907. 

The  poison  through  whose  inoculation  syphilis  is  produced  occurs 
only  within  the  human  organism,  where  it  is  al()ne  reproduct-d,  and  is 
communicated  to  otliei-  individuals  oidy  l)y  direct  or  in<lirect  transfer. 
Metschnikoff,  Koux,   Lassai,  and  Xeisser  have  succeeded  in  conveying 

syphilis  to  anthrapoid  apes  (the  chimi)an/ee)  thnmgli  the  i -nlatiou  <d' 

syphilitic  tissue.     When  imphinted  in  an  organism  the  infective  agent 
.    41 


042 


THE    PATHOGENIC    FISSIOX-FUXGI. 


excites  infliimmatory  processes  of  the  most  varied  intensity  and  extent — 
from  a  simple  local  transitory  liypememia  to  the  prodnction  of  large  ex- 
udates or  tumor-like  granulations,  or  extensive  hyperjilasias  of  connec- 


FiG.  489.— Initial  sclerosis  (alcohol,  hfpmatoxylin,  eosin).  o,  Coriiim,  slightly  inflamed:  ?),  initial 
sclerosis;  connective  tissue  inflltrat«d  with  cells;  c,  rupture  of  the  cells  into  the  epithelium ;  t/,  f,  lymph- 
vessels  lilletl  with  round  cells.     :■:  S.\ 


tive  tissue..    The  child  of  a  mother  infected  with  syi)hilis  may  receive  the 
infection  through  the  placenta. 

If  the  first  focus  of  inflammation  develops  at  the  point  of  infection, 
which  is  usually  located  in  the  skin  or  mucous  membranes  (mouth, 
throat,  mucosa  of  genital  apparatus),  there  is  formed  first  a  paj)ule 
which  spreads  toward  the  surface,  and  within  eight  to  ten  days  after  its 
appearance  forms  scales,  or  ulcerates  and  secretes  a  small  amount  of 

serous  or  purulent  fluid  Avhich  di'ies 


^^'^--v^; 


.m\'^ 


m 


to  a  scab ;  at  the  same  time  its  base 
l)ecomes  hardened  and  forms  a 
thick  disc-like  or  a  thin  parchment- 
like deposit  in  the  skin.  Occasion- 
ally a  vesicle  is  also  formed,  and 
this  becomes  an  erosion,  and  then 
an  ulcer  with  scanty  secretion  and 
having  an  indurated  base.  In 
still  other  cases  an  ulcer  is  first 
formed,  and  the  base  becomes  in- 
durated subsequently. 

The  induration  is  called  the  in= 
itial  sclerosis  or  the  Hunterkm  in- 
duration (Fig.  489,  h) ;  the  ulcer  is 
known  as  a  hard  chancre.  The 
former  is  caused  essentially  by  a 
collection  of  small  round  cells  (Figs. 
4S9,  h;  490,  «)  in  the  spaces  of  the  connective  tissue.  Occasionally 
epithelioid  cells  (Fig.  490,  h)  and  isolated  giant-cells  are  also  formed  (c). 


% 


FtG.  490. -Section  from  a  syphilitic  initial  sclero- 
sis (alcohol,  alum  cjirmine).  a,  Uound-oell  inflltra- 
tion;  /j,  large  mononuclear  formative  cells;  c,  mul- 
tinuclear  giant  cells.     X  350. 


I 


SYPHILIS.  643 

Willi  Ihese  changes  the  height  of  the  process  is  reached  ;  t  lie  -ivaler  piirl. 
of  the  tissue  disiiilegrales  and  ulcerales,  or  is  ahsorhcd  alter  (lisiiitcgr;i- 
tion.     A  part  of  the  cells  are  utilized  in  the  formal  ion  of  s<-ar  tissu*-. 

Within  the  area  of  the  initial  sclerosis  and  its  iniinediwte  n«'iglilM.r- 
hoodthe  lympli-vessels  (Fig.  489,  </,  c)  are  dilated  iiimI  lilled  witlileiico- 
cytes.  Later,  after  the  lai)se  of  a  certain  lengtli  (.1  lime  llie  lympli 
glands,  the  skin,  and  the  nincons  niend)ianes  heeonie  iii\(.lved  in 
intlaniniatory  jjrocesses  (  symptoms  of  tlu'  secondary  stage  ).  Still  later, 
there  follow  syphilitic inllammat ions  of  tlu^  internal organsand  tlie  hones 
(tertiary  stage).  These  are  in  i)art  like  other  non-syphilitic  inllamma- 
tious,  but  special  forms  of  granulation  tissue  aie  sometimes  produced. 
The  syphilitic  atfections  of  the  skin  which  are  grouped  under  tlie  term 
syphilides  form  sometimes  only  red  spots,  sometinu's  laiger  or  smaller 
papillary  elevations  which  may  be  associated  witli  tlie  foiniation  of  vesi- 
cles and  pustules  as  well  as  with  the  i)roduction  of  scales.      Accordingly, 


—f 


^ ''    -r*    *4.  •     **^»'V 


6-  '>v^  -(-^^"4'^> 


r 

c 


mjK--" 


^*<:c2b''    ^ 


■>^^'-- 


Fig. 491.— Condyloma  latum  ani  (alcohol,  Bismarck-brown),  a.  Horny  layer;  /).  mucous  layer  of  tho 
epidermis;  c,  corium;  d,  loosened  liorny  layer  infiltrated  with  small  cells;  e,  swollen, /,  swollen  and  In- 
flltrated  mucous  layer ;  (/,  epiihcli:!!  criis  containing  round  cells;  /i,f;ranular  ma.saes  of  coa^^ula;  (.swollen 
papillary  body  infll'tratfid  with  nils  iin.l  fluid  ;  h,  cx^rlum,  swollen,  and  inllltrated  with  cells,  lluld  and  coujf- 
ulated  albumin;  I,  dilated  lyin|ili-v(-M  is  filled  with  dots;  m,  sweat-fjlands.     X  1">(I. 

the  different  forms  of  cutaneous  syphilides  lia\c  been  called  by  (iilVeivnl 
names,  as  follows:  Jioseo/a  HjiphUiiic<i,  and  jKijin/ar,  rrsimhir,  jnisln/nr, 
and  ulcerative  si/philldes  as  well  as  a  jhsoriosis  siijihililicut.  A  common  ele- 
ment in  all  these  atfections  is  a  more  or  less  marked  inllammat  ion, 
Avhich  is  characterized  ])articularly  by  a  tissue-intill ration  :iiid  in  pail 
also  by  proliferation.  Thus,  for  example,  in  the  hirf/r  jxi/tii/dr  si/p/iiliilr 
ov  condi/Joma  latum  there  is  a  beet-like;  elevation  of  the  skin  caused  by 
an  infiltratiou  of  the  papillary  body  (Fig.  401,   /),  the  coriiim  (/.),  and 


644 


THE    PATHOGENIC    FTSSIOX-FrXGI. 


^.?^^ 


% 


v"*^    n^         -'i» 


/ 


y^ 


Fig  49^  — Aremn? )  ( IK  ephalitis  svpbihtioa  ffummosa  (MiiUers  nuid  aUobol,  h  em  itowliii).  a. 
Brain  cortex  h  iiuk  i  ineiiiiijt  ^  t  ^eln  siiirourKkd  l)\  celliilii  exiuiit  I  fre>,li  ctllulir  ffriiiulation 
tissue;  (?i  flhiocLllul  ii  ^i  iiuildti  )n  tishiu  (t  <  is(  ittd  /ranuU  ion  tissiu  i  irteij  vitti  markeillv 
thickeni  (i  imiiu  I  mcl  iU\(  iiiai  i  inflltrited  with  (t  IK  f  cellular  lufllti  iti  )n  of  the  pi  i  she  iths  of  the  cor- 
tical vesMN  f,  pt  rn ISC  ul  II  CLllulir  inliltmtion  of  lUetoiticdl  sub-5t  iiKi  </  diliUM  1\  spreiding  cellular 
InQltratiou  iin  i  im^  the  biain  &uhst  inti       X  14 


<^:sSMr 


^jw?.'.' 


^^-■ 


1  I.;.  4y3—.Syi)luli.s  of  tlu:  skull-cap.  a,  IViiostc-um;  h,  bouv  trabt-cukr;  c.  .sinall-ccIK-d 
mnitration  of  the  marrow;  d,  necrotic  infiltrated  marrow-tissue;  e,  periosteum  proliferating  into 
the  bene;  /,  fibrous  endosteum;  g,  osteoclasts  and  Howship's  lacunae.       X  40. 


.SYiMiii^is.  (;45 

also  tlio  epithoHnm  {e,  f,  g,  h)  with  cells  and  a  (luid  cxudalc  wliicli  cna-ii- 
latos,  causing-  liaidcnin«;-  of  the  tissue.  If  (he  horny  layer  (tf  llic  ejMdVi'- 
lais  becomes  macerated,  these  masses  of  exmhite  may  appear  np<.n  ilir 
surface,  and  give  rise  to  a  moist  contlition  of  the  condylnma.  In  iIm- 
pustular  syphilides  tlie  inilannuation  leads  to  a,  i>nrulenl  liipM-fact  ion  ui" 
the  ei)itlielium,  and  in  llie  nlccialing  foiins  also  of  thepapillar.x  l..,(|y 
and  of  the  corium,  so  that  iilcci-.s  result. 

Intlanimatory  changes  similar  to  those  in  llie  skin  :ii»|)ear  in  tin; 
secondary  stage  of  syphilis,  also  in  the  mucous  membranes,  jiarl  i(  iilarly 
of  the  month,  throat,  and  res])iratory  passages. 

The  syphilitic  lesions  of  the  tei'tiary  stage,  api)eaiing  in  the  inli-rnal 
org-aus,  in  the  glands,  Ixmes,  muscles,  subcutaneous  and  submucosal  tis- 
sues, in  the  meninges  of  the  biain,  etc.,  in  so  far  as  they  <'onsist  not  only 
of  slight  degenerative  and  inllammatoiy  ])roccsses  or  li>  perplasias  of  «-on- 
iiective  tissue  without  characteristic,  feat  u  res,  ai)j)(^ar  as  formations  Mliicli 
are  usually  designated  as  gummata  or  as  syphilomata  (NirelH.w  ).  In 
its  early  stages  the  gumma,  as  well  as  the  broad  condyloma,  re]tresents 
au  inflammatory  process  localized  to  one  tissue-area ;  i»ut  the  gumma  is 
usually  more  rich  in  cells  and  undergoes  in  part  a  suppuration  <»r  cheesy 
necrosis  (Fig.  492,  d.,),  while  in  other  portions,  particularly  the  iieiijih- 
eral,  granulation  tissue  (d)  and  later  connective  tissut^  (f/i)  are  devel- 
oped. The  gumma  occurs  particularly  in  the  i)eriosteum  (Fig.  4(».'})  and 
membranes  of  the  brain  (Fig.  492),  as  well  as  in  the  parenchymatous 
organs  of  the  abdomen,  especially  in  the  liver  (Fig.  494,  a,  b),  sj)leen, 
and  in  the  testicles. 

In  the  meninges  of  the  brain  and  spinal  coid  syphilitic  inllammat  ions 
lead  in  part  to  cicatricial  thickenings  and  in  ]»art  to  the  formation  of  en- 
capsulated caseous  masses.  Periosteal  syphilis,  which  occurs  nu)st  irv- 
quently  in  the  tlat  bones  of  the  skull-cap  (Fig.  493),  and  often  in  the 
facial  bones,  and  the  gi-eat  long  bones  (the  til)ia),  and  may  extend  over 
the  greater  part  of  the  skeleton,  shows  likewise  the  chaiacter  of  a 
granulomatous  inflammation  which  leads  to  the  foiination  of  scar-tissue 
and  new  bone,  so  that  osteophytes  or  hy])erostosis  may  I'csnlt.  'J'ne 
severe  forms,  as  represented  l>y  the  formation  of  gummata,  have  a 'de- 
structive action  upon  the  bones  and  lead  to  caries  and  necrosis.  The 
fresh  inflammatory  focus  appears  as  a  gray  translucent,  yellow  or  grayish- 
white  pus-like  focus  suiroundcd  by  hypeiaunic  tissue,  having  its  seat  in 
the  periosteum  from  which  it  may  also  extend  to  the  marrow.  Tlu'  yel- 
lowish foci  consisting  of  masses  of  small  cells  (Fig.  49;>,  r)  may  <lie,  the 
cells  losing  their  nuclei  (d),  and  in  such  i)laces  neci'osis  of  the  bone  may 
also  result.  Inli\  ing])eiiosteal  and  endosteal  tissu*'  there  oeeuis  a  new- 
formation  of  ccmnective  tissue  (',/),  which,  with  the.  foiination  of  multi- 
nucleated osteoclasts  (r/)  and  the  formation  of  llowship's  lacuna-,  leads 
to  destruction  of  the  bony  trabeculte.  In  the  case  of  a  healing  of  tlui 
process  this  connective  tissue  inay  be  again  changed  into  boiu'. 

In  the  liver  the  syphilitic  lesions  lead  to  the  formation  of  ladiating 
connective-tissue  scars  (Fig.  494,  b,  r,  d),  which  often  cm-lose  cheesy  rem- 
nants of  the  original  intlammat(n-y  focus  (a),  that  is,  a  caseous  gumma. 
The  process  is  similar  in  the  other  organs,  for  example,  in  the  tesiicies 
and  in  the  spleen. 

The  disintegration  of  syphilitic  foci  of  the  skin  and  subcutam-ous  tis-^ 
sue,  as  well  as  of  the  mucosa  and  sulnnucosa,  leads  to  the  formation  of 
ulcers,  which,  in  the  case  of  the  mucous  membran«'S,  occ-nr  most  fre- 
quently in  the  region  of  the  mouth,  throat,  and  the  upper  lespiratory 


646  THE    PATHOGENIC    FISSIOX-FUNGI. 

tract  (Fig.  495,  a).  In  the  neighborhood  of  the  ulcers  arising  in  mncous 
membranes  there  are  not  infrequently  formed  ijapillary  proliferations 
(Fig.  495,  b,  c). 

The  cause  of  the  frequent  disintegration  and  necrosis  occurring  in 
syphilitic  inllammations  lies  in  the  peculiar  character  of  the  exciting 
cause  of  the  disease.  A  second  factor  may  also  be  largely  responsible 
for  this  manner  of  termination — namely,  the  extensive  participation  of 


/- 


Fig.  494.— Gumma  hepatis  (alcohol,  alum  carmine) .  a.  Caseous  nodule ;  b,  homogeneous  connective 
tissue ;  c,  connective  tissue  with  remains  of  liver  tissue ;  d,  connective-tissue  bands  radiating  into  the 
liver  tissue;  e,  cellular  focus  at  the  edge  of  the  caseous  nodule;  /,  cellular  focus  within  the  connective- 
tissue  rays ;  »,  liver  tissue.    X  12. 

the  blood-vessels,  particularly  of  the  arteries,  in  the  inflammation. 
When  a  syphilitic  inflammation  leads  to  the  formation  of  granulation 
tissue  or  to  a  connective-tissue  hyperplasia,  the  vessel-walls  also  become 
thickened,  x)articularly  the  intima  (Fig.  492,  e'),  so  that  the  vessel-lumen 
is  narrowed  and  nob  infrequently  completely  closed.  Occasionally  the 
syphilitic  process  is  localized  chiefly  in  the  vessels. 

Besides  the  peculiar  foci  of  inflammation  which  point  to  a  localiza- 
tion of  tlie  exciting  cause  of  syphilis,  there  not  infrequently  occur  in 
individuals  who  have  suffered  a  syphilitic  infection  specific  ilcgennaiions 
of  the  central  wrroii.s  .si/stnn  (tabes,  i)rogressive  paralysis),  which  are  asso- 
ciated with  prolileralions  of  neuroglia.  Nevertheless,  these  affections, 
though  regarded  as  the  sequelw  of  syphiHs,  present  histologically  no  pecul- 
iarities characteristic  of  syphilis,  and  occur  in  the  same  form  in  other 
indi\  idnals  who  have  never  had  a  syphilitic  infection. 

Hereditary  syphilis  is  characterized  chiefly  by  peculiar  tissue -changes, 
which  difler  considerably  from  the  manifestations  of  acquired  syphilis, 
but  clianges  also  occur  which  correspond  to  the  latter.  In  the  skin 
liereditaiy  syi)liilis  may  cause  macular,  papular,  and  pustular  syphi- 
lides  whieli  may  lead  to  ulceration.     The  liver,  kidneys,  adrenals,  and 


SYPHILIS. 


G47 


the  bones  may  show  pironnisciilit'd  uc- 
croticfoi'i  or  inHainiuatorv  eclhilar  iiilil- 
tratioiis.  The  spU'cii  is  usually  iiioic  or 
less  eiilar.ued,  and  in  indi\idiial  cases 
may  attain  ten  times  its  normal  volume. 
In  tlie  liver  there  occur  intiavascular 
and  perivascular  collections  of  round 
cells  which  often  collect  in  small  closely 
packed  foci;  associated  Mith  these  there 
is  a  periportal  new-fornnition  of  con- 
nective tissue,  Tliere  is  also  a  diffuse 
liyperplasia  of  connective  tissue  throu<;h- 
out  the  entile  liver  (Fii;".  49(j,  a,  h),  g^iv- 
ing  to  the  organ  a  tiiin  consistence  and 
a  peculiar  yellowish-brown  color.  Fur- 
ther, there  is  also  a  i)rol  if  oration  of  con- 
nective tissue  limited  to  the  perii)ortal 
tissue.  The  lungs  may  present,  through- 
out or  in  part,  a  dense  gray  or  grayish- 
white  structure  resembli)ig  that  of  sar- 
coma tissue.  This  appearance  is  due  to 
the  formation  in  the  altered  area  of  a 
cellular  connective  tissue  (Fig,  497,  a, 
b)  which  contains  only  imperfectly  de- 
veloped alveoli  (e,  e^)  and  bronchi  (<], 
dj)  or  none  at  all.  In  cases  of  slight 
severity'-  there  exists  only  a  thickening 
of  the  peribronchial  and  perivascular 
tissue  and  interalveolar  septa,  in  part 
associated  with  an  accumulation  of  desquamated  epithelium  in  the 
alveoli.     In   the   kidneys  and  testicles  the  supporting  connective  tis- 


-Syphilitifi  ulceration  of  the 
t  ion  thrniifrli  the  larynx 
and  trarli.a.  a,  Iliii  :  I,,  itiiiki-ninjrs  and 
impillMiy  pPilifiTiitinns,,!]  tin-  .-pitrldiils;  c, 
tliickftiinjrs  and  papillary  i>ic>lifi'riilions  on 
the  left  wall  of  the  larynx  and  the  supe- 
rior thyro-arytenoid  ligament.  Natural  size. 


3S-'- '. 

P^. 


m 


M 


Fig.  496. -Induration  of  the  liver  in  congenital  syi.hills  (Miiller's  tliiid,  hieniatoxylln.  eosln).    o,  Hr- 
pertrophic  periportal  connective  tissue;  h,  indurated  gland  tissue  inflltrated  with  connective  Ussue;   c, 

collections  of  cells.     X  KM). 


648  THE    PATHOGENIC    FISSIOX-FUXGI. 

sue  may  likewise  be  inereased  in  ])]a(.'es,  and  abnormally  rich  in  cells. 
JSypJi His  also  often  causes  in  f/kouhdar  on/tois  a  patliolofjical  (leiyJoiment 
of  the  eonneeiive-tissue  elements  and  codcctions  of  cells,  while  the  epi- 
thelial tissues  are  retarded  in  their  development.  In  the  blood  the 
number  of  white  corf>uscles  apj)ears  often  to  be   increased.     Finally, 


FiQ.  497.— Changes  in  the  lung  in  congenital  syphilis  CMuller's  fluid,  htematoxylin.  eosiii  i.  a.  Prolifer- 
ating stroma  rich  in  cells;  b,  cellular  granulatioii-foci ;  c,  artery  with  thickened  adventitia :  </,  rt,  gland- 
like bronchi,  which  in  part  U1,)  contain  desquamated  epithelium  and  round  cells;  e,  Cj,  alveoli,  which  in 
part  (Cj)  contain  desquamated  epithelium  and  round  cells.     X  52. 

there  not  infrequently  occur  in  the  bones  disturbances  of  endochondral 
ossif  cation,  which  are  characterized  chiefly  l)y  irregularity  in  the  forma- 
tion of  the  medullary  cavity  and  in  the  deposit  of  lime-salts  in  the  car- 
tilage, and  lead  to  disturbances  in  the  structure  of  the  subchondral 
spongy  bone-substauce.  Through  the  formation  of  granulation-tissue 
proliferations  which  undergo  caseous  necrosis,  larger  defects  may  arise 
in  the  bone  substance. 

It  has  been  assumed  by  many  authors  that  syphilis  can  be  transmitted  to  the 
foetus  not  only  through  the  mother  but  also  from  the  father  through  the  sj^erm,  and 
that  the  latter  event  can  occur  without  the  mother  becoming  infected  witli  syphilis. 
Matzenauer  opposes  this  view  and  declares  that  no  clinical  observations  exist  that 
exclude  the  transmission  of  lues  through  the  mother.     (See  §  18.) 

According  to  Blaschko  (Berl.  kiin.  Woch.,  1908),  Wassermann's  "  complement- 
binding  "  test  for  syphihs  is  rehable,  in  that  it  never  gives  positive  findings  in  the  cer- 
tain absence  of  syphihs.  Complement  is  added  to  an  inactive  serum  obtained  from 
apes  previously  treated  with  organ-extracts  or  serum  from  a  syphihtic  man.  After  a 
certain  time  the  serum  thus  treated  is  tested  with  an  inactive  specific  hsemolj'tic 
serum  and  its  corresponding  red  cells  to  see  if  the  complement  is  wholly  or  partly 
anchored.  Inhibition  of  haemolysis  occurs  in  the  case  of  a  serum  resulting  from  the  use 
of  syphihtic  material. 

Literature, 

(S!/2)hnis. ) 

Aschoflf:  Akute  Entztmdung  der  Leber  und  Xebennicren   bei  kong.  Syph..     \erli.  d. 

D.  p.  Ges.,  vi.,  1904. 
Bender:  Zusammenfassender  Bericht  iiber  die  Bacillen  d.  Syi:)hilis.     Cbl.  f.  Bakt.,  1SS7. 
Campana:  Dei  morbi  sifilitici  e  venerei,  Genova,  1889. 

Chotzen:  Btreptokokken  bei  hered.  Syph.     Vierteljahrsschr.  f.  Derm.,  xlv.,  1SS7. 
Dohrn:  Zur  Frage  der  hereditaren  Syphilis.     Deut.  med.  ^yoch.,  1892. 


LEPROSY.  (-,49 

Doutrelepont:  Syphilis  u.  SmcjiinahaiilU-n.     Vit-r((Ij:ilirssrlir.  f.  Derm.,    xiv.     ISS?; 

Stni-Iokokken  u.  Bat'illon  Ix-i  luTcditairr  Svphilis.     (Viitrl>l.  I'.  Hakl..  ii.,  lSS7. 
V.  During':   Hereditare  Sypliilis.     ];ulfiil)ur.u;"s  [{calciicykloi)..   ISii;)  (Lit.). 
Ehrmann:    Iiiitialsklfms^-  dos  IVnis.     A.  f.  Derm.,  (is' Hd..  I'HIJ. 
E'ichhorst:    i:U-phaiui:i>is  syphiUtica.  dor  Lii)|u-ii.      N'irch.  Arch.,   ]A\   H.I.,  1S<)3. 
Finger:    Die  SypliiHs  als  Infect ioiiskrankhoif  voiii  StaiidiMinktc  iUt  iModcnicii  Baktc- 

riolof^ie.     Arch.  f.  Derm.,  xxii.,  ISiK);    Die  Syi)liili.s  u.  (he  veiierischeii  Kraiikheiteii, 

Wien,  11)01:    Die  Vcrerl)un.<:;  der  Sypliihs,  Wieii.  1S<)S  (lat.). 
Fournier:  Die  Vererbung  tier  Svphihsj  Wien,  1S<»1;    Svphihs  hereditaria  tarda    Wien. 

1S94. 
Hecker:  Beitr.  z.  Hist.  ii.  Path.  d.  congen.  Svphihs,  Xanmhm-i:,   1S9S,    n.  D.   med. 

Woch.,  1902. 
Heller:   Die  Lun>;euerkrankimg  bei  anceb.  Syphihs.     Dent,  .\rcli.  f.  klin.  Mech,   is.sT. 
Heller,  J.:    Syphihniycina  hereditaria.      A.  "f.  Derm.,  (i,')  Bd.,  1{»0:5. 
Hochsinger:  St'.idien  (ibcr  die  hereditiire  Syphilis,  i.,  Wien,  ISHS  (I,it.). 
Hiigel  u.  Holzhauser:  Sypliihsimpiuiiiien  am  'i'iiier.     Arcii.  f.  Derm..  .")()  Bd  ,  I'.tDO. 
Hutinel  et  Hudelo:  Et.  sur  les  lesions  syphiliticines  du  foie  ciiez  h-s  foetus  et  lea  nou- 

veaunes.     Arcli.  de  med.  exp.,  isyo. 
Kassowitz  u.  Hochsinger:  Ueber  einen  Mikroorganisnnis  in  den  (ieweben  herediliir 

svphilitischer  Kinder.     W^ien.  med.  Blatter,  ISSG. 
Lang:   Vorl.  iib.  Pathol,  u.  Ther.  d.  Syphilis,  Wiesbaden,  1S9(;. 
Lang  n.  TJllmann:  Syphilis.     Ergebn'.  d.  allg.  Patii.,  v.,  1900  (Lit.\ 
Lassar:   Impfversiiche  an  anthropoiden  Affen.     lierl.  klin.  Woch..  190;}. 
Lustgarten:  Syphilisbacillen.     Wien.  med.  Wocli.,  1884;   Die  Svphilisbacillen,  Wien. 

1.SS.3. 
Markuse:  Stand  der  Syphilis-  u.  Smegniabaeillen.     Vierteljahrss<'lir.  f.  Denn.,  xv., 

1SS8. 
Matzenauer:  Die  Vererbung  d.  Syphilis.     A.  f.  Derm..  Ergiinzungsh..  190.'i. 
Mauriac:  Lecons  sur  les  maladies  v^neriennes,  Paris,  1890. 
Metschnikoff  et  Roux:  Et.  exper.  sur  la  syphilis.     Ann.  del'Inst.  Pasteur,  1903,  u. 

1).  med.  AVoch.,  1904. 
Meyer:  Svphihs  d.  Centralnervensystems.     Cbl.  f.  allg.  Path.,  ix.,  1898  (Lit.). 
Mracek:  Atlas  der  Syi.hilis,  Mimchen,  1898. 

Miincheimer:  Die  extragenitale  Sypliilis.     Areh.f.  Derm.,  40  Bd.,  1.S97  (Lit.). 
Neisser:   Tebertragung  d.  Sypliilis  auf  Affen.     D.  med.  Woch.,  1904. 
Neumann:  Die  Vererbimg  der  Sypliilis.     Arch.  f.  Derm.,  xxiv.,  189S. 
Paris  ft  Salomon:  Org.  hematoiioiet.  chez  I'inf.  syph.    A.  ile  med.  exp.,  1904. 
Pi-ocksch.:  Die  Literatur  iiber  die  venerischen  Kranklieiten.  Bojin,  1889  91. 
Runipf:   Die  sviiliilitischen  Erkrankungen  des  Nervensystems,  Wiesbaden.   1887. 
Stroebe:  Zur  Histologie  d.  congen.  Nieren-  u.  Lvmgcnsyphilis.     ("bl.  f.  allg.  Path.,  ii., 

1891. 
Surico:  La  Sifilide  congenita.     Giorn.  Ital.  della  Mai.  Ven.,  1900. 
Virchow:  Die  krankhaften  Geschwiilste,  ii. 

Waelsch:  Die  Bacillenbefunde  bei  Sj^hilis.     A.  f.  Derm..  08  Bd..  1904  (Lit.\ 
Wassermann,  Neisser  u.  Bruck:    Eine    Serodiagnosti.sche    Reaction  bei  Syphilis. 

Dent.  med.  Woch.,  190G;   Z.  f.  Hvg.  u.  Inf..  .")")  Bd..  No.  3. 
Zeissl:  Svphilis.     Eulenburg's  Realencvkloi).,  xxiii.,  1900;    Lehrb.  d.  vener.   Krankh.. 
1902.' 

§17,3.  The  Bacillus  lepree  ((U'scrilx-d  l»y  Ncissci-  in  LS7!»  and  issj, 
aud  by  Armauer  Hansi'ii  in  ]SSU)  is  a  siiimI!  sIcikI.t  l.acilliis,  liom  I  m  «;•. 
long.  It  is  regarded  as  tlie  cause  of  leprosy— also  called  r/rit/iaiiliti.sl.s 
Gnvcornm.  It  is  found  constantly  and  in  gical  nnnduMs  in  liic  di.scascd 
tissues  (  Figs.  4«>s,    4!M),  .-iOO) 

The  foci  of  disease  in  leprosy  are  in  general  <-liaract('rizcd  By  a  pro- 
liferation (Fig.  4!>S)  Avhich  consists  of  cells  of  <lijferent  sizes  and  of  a 
fibrous  ground  tissue.  Tlu^  bacilli  lie  sometimes  between  (d,  sometimes 
in  the  cells  (c,  cl),  andintln^  latter  appear  usually  in  such  great  nnmbers 
that  the  cells  may  become  greatly  swollen  (d)  and  in  jiarl  become 
changed  into  mon()-  and  multinnclcar  giant-cells  (  Fig.  4!M»).  Tlie  latter 
occasionallv  enclose  large  vac noles  which  <-ontain  great  nnmbers  of  bacilli 
as  well  as^the  granular,  thready  detritns  of  the  li<|nelie(l  protoplasm. 
The  nuclei  remain  preserved  for  a  long  time,  ami  are   piessed  to  the  pe 


G50 


THE    PATHOGENIC    FISSIOX-FUXGI. 


ripliery  by  the  vacuoles  containing  the  bacilli.  Later  they  are  destroyed, 
so  that  the  entire  cell  becomes  changed  into  a  vacnole  containing  bacilli 
("Fig.  499).  The  cells  in  which  the  bacilli  lie  are  in  part  the  original 
cells  of  the  tissne,  and  in  part  newly  formed  cells. 


Fig.  498.— Tissue  from  a  leprous  nodule  (alcohol,  fuchsin,  methylene-blue).  a,  Flbrocellular  tissue ; 
b,  round-cells ;  c,  medium-sized  cells;  d,  very  larf?e  cells  tilled  with  bacilli ;  e,  free  bacilli,    x  200. 

Fig.  499. — Giant-cells,  with  vacuoles  containinfc  bacilli,  from  leprous  proliferations  of  the  nasal  mucosa 
(alcohol,  Gabbefs  stain).    X  400. 

The  bacilli  are  surrounded  by  a  slimy  envelope  (Xeisser),  and  react 
to  stains  in  much  the  same  manner  as  do  tubercle -bacilli.  The  same 
staining  methods  may  therefore  be  iTsed  for  the  former  as  for  the  latter. 
The  stained  bacilli  often  show  clear  si)ots  or  appear  as  if  made  up  of 
stained  grannies. 


•'^^^^^I^^^S^^"'^^  ^^''"^'  ''^^"''■""" 


Fio.  .5nn.-Sf(tii)n  tl)nm<rh  a  leprous  nodule  of  the  skin  (alcohol,  Gabbet's  method),  a.  Epidermis;  h, 
cortum:  c.  han-foliKi..;  (/,  leprous  fcx-us  in  the  neighborhood  of  the  hair-follicle;  e,  duct  of  sweat-gland ; 
r,  leprous  Hdi  I  Ml.-  about  duct  of  sweat-gland ;  g,  leprous  foci  in  the  neighborhood  of  sweat-gland  ;  h,  leprous 
locus  having  n.icsin-.ial  relation  with  any  of  the  specific  skin  structures  ;  i,  foci  of  bacilli.     .X  32. 


I.KIMiOSV. 


nr.i 


Attempts  to  cultivate  lepra  bacilli  have  led  to  no  important  nsuUs, 
since  the  bacilli  obtained  in  the  cultures  could  not  positixcly  bo  idcnfi- 
lied  as  lepra  bacilli.  In  the  transplantation  of  lc|)rons  tissues  into  ani- 
mals there  occurs,  of  coujse,  a,  transplant inji-  ol"  llie  bacilli,  Init  tlio 
latter  do  not  multiply  and  lu)  i)ro<;ressi\  c  disease  results. 

The  infection  of  man  takes  place  by  a  direct  or  indiiect  transfer  from 
individual  to  individual.  The  nasal  secretion  is  especially  infectious 
(Sticker),  particularly  when  leprous  supi)urations  are  i)resent  in  tlie 
nose.  In  the  case  of  "^leprous  allecti(»ns  of  the  resjiiratory  tract  the  spu- 
tum nuiy  contain  bacilli;  and  in  tlu^  bn-ma1ion  of  nodules  and  ulcers  in 
the  skin  the  secretions  from  the  latter  may  also  contain  the  bacilli. 
Contagion  seems  to  lesult  most  freipiently  fi-om  the  nose  (  St  icker ) ;  in 
favor  of  this  view  speaks  the  fact  that  the  anterior  nasal  region  is  usu- 
ally involved  very  early.  The  bacilli  are  spiead  throughout  the  body 
chiefly  by  the  lymphatic  system;  Imt  they  may  also  get  into  the  blood- 
stream. 

Besides  the  nose,  the  skin  and  the  peripheral  nerves  are  ch icily  con- 
cerned in  the  disease;  but  the  bacilli  may  multiply  in  other  tissues,  as 


y  L>A 


Fig.   SOl.-Leontiiisisleprosa.     (After  (i.  Miiiicli.) 


in  the  testicles,  liver,  in  the  ganglia,  and  in  the  spleen 
rise  to  foci  of  disease  in  the  oigans. 

At  the  place  of  colonization  the  bacilli  excite  iullani 
sue-proliferation.  (Jranulation  tissue  containing  blood-v 
this  remains  for  a  longtime  in  a  condition  which  is  ( 
great  richness  in  cells,  and  forms  the  basis  I'oi-  no<hil(^ 


,  thereby  giving 

nialion  with  tis- 
I'sscls  is  foinn-d  ; 
haracteri/.ed  by 
;  and  lnnioi>   in 


652  THE    PATHOGEXIC    FISSIOX-FUXGI. 

the  sUin  and  nose  and  for  spindle-shaijed  thickenings  of  the  nerves,  and 
is  the  cause  of  the  irritation  and  laier  of  the  dei;eneration  and  destruc- 
tion of  the  nerve-tibi-es.  The  bacilli  and  the  tissue-proliferations  caused 
by  their  multiplication  often  group  themselves  in  the  skin  about  the  hair- 
follicles  (P'ig.  500,  d),  the  ducts  (/'),  and  the  coil  (ff)  of  the  sweat- 
ghiuds,  but  such  a  relationship  is  not  always  to  be  seen  (h).  Moreover, 
the  bacilli  may  penetrate  into  the  blood-vessels,  the  hair-follicles,  and 
sweat-glands  (Touton),  and  thence  on  to  the  surface  of  the  skin.     Infec- 


FlG.502.-Li'|iiu  atia'stli.tiru  ulcrioMi  of  the  leg  ami  f(X)t.     (After  (i.  Miiiich.) 

tion  of  the  arterial  walls  causes  a  proliferating  arteritis,  by  which  the 
walls  become  greatly  thickened  and  the  lumina  narrowed.  In  the  ner- 
vous system  the  bacilli  are  found  both  in  the  connective  tissue  and  in  the 
nervous  elements,  particularly  in  the  ganglion  cells  (Sudakewitsch). 
The  cells  occupied  by  them  undergo  degeneration  in  the  course  of  time, 
occasionally  with  hydropic  swelling  and  the  formation  of  vacuoles. 

The  tissue-proliferations  caused  by  the  growth  of  the  bacilli  may 
almost  wholly  disajjpear  through  the  disintegration  and  absorption  of  the 
cells  after  the  condition  has  lasted  for  years;  but  there  always  remain 
indurations  rich  in  cells  and  pigmentations  in  the  skin.  Caseation  never 
takes  place. 

LeproHy  of  the  sl-in  occurs  especially  in  the  face,  on  the  extensor  sur- 
face of  the  knees  and  elbows,  as  well  as  on  the  back  of  the  hands  and 
feet.  It  begins  with  the  formation  of  red  spots  which  either  a  anish,  leav- 
ing pigmented  spots  behind,  or  become  elevated  into  nodules  of  a  brown- 
ish-red color  {lepra  tuherosa  sive  tiibcrculo.sa  sire  no<lo,sa).  In  the  region 
of  the  red  spots  the  tissue  contains  large  numbers  of  bacilli  (  Philipson), 
which  for  the  most  part  lie  within  the  vessels,  and  already  at  this  stage 
the  prolifeiation  of  the  tissue  can  be  demonstrated.  According  to  the 
investigati(nis  of  Miiller  the  vesicular  eruptions  which  occur  in  leprosy, 
and  weie  foiinerly  regarded  as  the  sequelte  of  the  leprous  disease  of  the 
nerves,  are  caused  by  the  presence  of  the  bacilli. 

The  nodules  may  leniain  unchanged  for  months,  or  they  may  increase 
in  size  and  become  confluent,  so  that  very  large  protuberances  may  be 
formed,  which,  because  of  the  distortion  of  the  face  thereby  occasioned, 
ha\e  given  occasion  for  the  designation /«ctVs  leontina  (Fig.  501). 

Through  eoderndl  influences  idcers  may  be  produced  which  show  no 
tendency  to  healing.  Kew  nodules  appear  occasionally  following  ery- 
sljjelatous  reddenings  and  swellings  of  the  skin.  The  glands  of  the  sub- 
maxillary and  inguinal  region  swell  to  form  very  large  nodules. 

Lcprosji  of  the   nerres   (h'pra  nerrorinn  sire  ancestJietiea)  leads  first  to 


LF.l'HOSV 


(M.i 


liyi)(M;i\stliosi;i  and  pain,  later  to  an.Tstliesia,  more  rarely  to  mol 
SI'S  in  the  re«;ion  of  t lie  aft'eeted  nerves.  The  furtlier  eonse<|nene 
disease  of  the  nerves  are  distnrhanees  uliieh  e\]>i-ess  theinselv 
skin  V)y  the  formation  of  vhite  and  br(»\vn  sjxtls  {Irpnt  nutrnlosn 
((ii(C,st/u'l/f(i.  iiu>rpha'((  nif/ni  rt  allxi),  and  in  the  hones  and  mi 
atiophy.  Since  tiiose  snl'feriii.u'  Irom  the  disease  arc  likely  1 
tiuMMselves  after  the  a])pcaiance  of  ana-stliesia,  nh-cis  arc  often 
at  a  later  jteriod  (Fij;s.  .")(►•_*,  TM\)  Avhich  canse  (h-cp  erosions  ; 
lead  to  the  loss  of  entire  i)halanges  {h'xn'ci  mutUan.s). 

Leprosy  of  the  skin  and  of  tlie  nerves  are  usnally  eond»ine 
larelv  do  they  occnr  alone.     Besides  the  nose,  skin,  and  ncrv»'s. 


V  par;il\  - 
■csof  I  lie 

.'S  ill   tlle 

,    iiiiiriiht- 

iscU-s  l.y 

injnr«' 

formed 


I;    moiT 
the  cen- 


•i-s  ill  Illflmml.    (Aft'T 


tral  nervons  system,  mueons  membranes,  cornea,  the  cartiia^ics. 
lungs,  spleen,  iymph-giands,  and  the  testicles,  hecom*'  diseased. 

In  Enrope  leprosy  is  confined  mainly  to  Noi-way,  Swt'den.  V\ 
the  Ilaltic  .Sea  provinces  of  Rnssia,  and  tlu'  coasts  of  the  .Mediterr 
but  occurs  spora<lically  in  other  regions.  It  occurs  \cry  fre(|Uc 
Hindustan,  China,  Sumatra,  Hoiiieo,  Java,  and  Mexico,  on  the  n< 
and  eastein  coasts  of  South  America,  in  I'pper  and  Lower  (Jni 
Cape  Colony,  and  on  the  northern  coast  of  Africa. 

Leprosy  is  prevalent  in  Mexico,  the  West  Indies,  and  in  the  PhilippiMcs.  a 
are  found  in  New  Brunswick  and  other  parts  of  Canada.  (  ases  :ire  also  .« 
tliroughout  the  United  States,  the  most  important  centres  Ix-mg  in  Louisiana, 


liver, 

illhUKl. 

aiie:iii  : 
iitU  in 
irtliern 
nea.   in 


ml  cases 
cat  ten.'* I 
Califor- 


654  THE    PATHOGENIC    FISSIOX-FUNGI. 

nia,  and  Minnesota.     According  to  a  Senate  report  of  1902,  there  were  at  that  time 
278  known  cases  of  leprosy  within  the  borders  of  the  United  States. 

Literature. 

(^Lcpra-hacilU.     Le])roHij. ) 

Arning:  Lepraimpfung    beim    Menschen.     Arch.    f.    Derm.,    1889,  Erganzungsheft', 

Lepra  mit  besond.  Berucksicht.  der  Uebertragung  durch  Hereditat  u.  Contagion. 

lb.,  xxih.,  1891. 
Babes:  Unters.  lib.  d.  Leprabacillus  u.  d.  Histologic  der  Lepra,  Berlin,  1898  (Lit.); 

Kultur  der  von  mir  bei  Lepra  gef.  Diphtheridee.     Cbl.  f.  Bakt.,  xxv.,  1899;    Die 

Lei)ra,  Wien,  1901. 
Bergmann:  Die  Lepra  in  Livland,  Stuttgart,  1897. 
Blaschko:  Die  Lepra  im  Kreise  Memel,  Berlin,  1897. 
Bonome:  SiiUa  l('i)ra  dei  polmoni.     Arch,  per  le  Sc.  Med.,  xii.,  1888. 
Bordoni-TJffreduzzi:  La  coltivaz.  del  bac.  d.  lepra.     Arch.  p.  1.  Sc.  Med.,  xii.,  1888. 
Czaplewski:  Aus  eineiu  Leprafall  geziichtete  Bacillen.     Cbl.   f.   Bakt.,   xxiii.,   1898. 
Damsch:  rel)ertra,iiuiii;sversiu-lie  v.  Lepra  auf  Thiere.     Virch.  Arch.,    92  Bd.,   1883. 
Doutrelepont  u.  Welters:  Yiseerale  Lepra.     Arch.  f.  Derm.,  34  Bd.,  1896. 
Ehlers:  Aetiol.  Studien  iiber  Lepra,  Berlin,  1896. 
Finger:  Lepra.     Ergebn.  d.  allg.  Path.,  vi.,  Wiesbaden,  1901. 
Gerlach:  Die  Beziehungen  zwischen  Hautflecken  u.  d.  Nervenerkrankung  bei  Lepra 

ana?sthetica.     Virch.  Arch.,  125  Bd.,  1891. 
Hansen,  A.:   Lepra.     Handb.  d.  pathog.  Mikroorg.,  ii.,  Jena,  1903. 
van  Houtam:  Cultivat.  of  the  Bac.  LepriE.     J.  of  Path.,  viii.,  1902. 
Joseph:  Viscerale  Lepra.     Arch.  f.  Derm.,  43  Bd.,  1898. 
Klingmuller:  Lepra  maculo-anresthetica. 

Kuhne:  Zur  path.  Anat.  d.  Lepra.     Monatsh.   f.  pr.  Derm.,  Erganzungsh.,  iii.,  1887. 
Leloir:  Traite  pratique  et  theorique  de  la  lepre,  Paris,  1886. 
Lie:  Zur  pathol.  Anat.  der  Lepra.     Arch.  f.  Derm.,  29  Bd.,  1894. 
Mliller:  Lepra.     Deut.  Arch.  f.  klin.  Med.,  xxxiv.,  1884. 
Munch:  Leju-a  u.  Vitiligo  im  Suden  Russlands,  Kiew,  1884-86. 
Neisser:  Bacillus  leprae.     Bresl.  arztl.  Zeitschr.,  1879;    Virch.  Arch.,  84,  103  Bd.,  v. 

Ziemssen's  Handb.  d.  spec.  Path.,  xiv.;   Structur  d.  Lepra-Bacillen  u.  -Zellen.  Cbl. 

f.  a.  Path.,  i.,  1890. 
Philippson:  Histologie  d.  hyperam.  Flecke  d.  L.  tuberosa.     Virch.  Arch.,  132  Bd.; 

Symbiose  d.  Tuberkelbacillen  mit  Leprabacillen.     lb.,  132  Bd.,  1893. 
Prus:  Verhalten  d.  Morvan'schen  Krankh.  zur  Lepra.     Arch.  f.  Psych.,  27  Bd.,  1895. 
Ramon  y  Cajal:  Sobre  1.  celulas  gig.  de  la  lepra.  Caceta  San.  de  Barcelona,  ii.,  1890. 
Rickli:  Zur  pathol.  Anatomic  d.  Lepra.     Virch.  Arch.,  129  Bd.,  1892. 
Scheube:  Die  Krankheiten  der  warmen  Lander,  Jena,  1903. 
Scholz  u.  Klingmuller:  Ziichtungsversuche.     Internat.  Lepra  Arch.,  1900. 
Sokolowski:  Zur  pathol.  Anat.  d.  Lepra.     Virch.  Arch.,  159  Bd.,  1900. 
Sticker:  Lepra.    Mimch.  med.  Woch.,  1897;  Arb.  a.  d.  K.Gesundheitsamte,  xvi.,  1899. 
Sudakewitsch:  Zur  patliol.  Anatomic  d.  Lepra.     Beitr.  v.  Ziegler,  ii.,  1887. 
Teich:  Kultur  d.  Leprabacillus.     Cbl.  f.  Bakt.,  xxv.,  1899. 
Thoma:  Anatomisches  iib.  Lepra.     Virch.  Arch.,  75  Bd.,  1871;    Deut.  Arch.  f.  klin. 

Med.,  47  Bd.,  1891. 
Touton:  Topographic  d.  Leprabacillen  in  d.  Haut.     Virch.  Arch.,  104  Bd.,  1886. 
Uhlenhut  u.  Westphal:  Histol.  d.  Lepra  tuberoso-anaesthetica.     Cbl.  f.  Bakt.,  xxix., 

1901. 
Unna:  Lcprastudien.     Monatsh.  f.  prakt.  Derm.,  Erganzimgsh.,  1885;  Dermat.  Stu- 

<lien,  i.,  Hamburg,  1SS6.     Deut.  med.  Woch.,  1886;   Virch.  Arch.,  103  Bd.,  1886. 
Virchow:   Die  kraukli.  (leschwiilste.  ii.;    Lepra  d.  Milz.     Berl.  klin.  Woch.,  1885. 
Wesener:  Zur  I'eltertragharkeit  d.  Lepra.     Beitr.  v.  Ziegler,  viL,  1890. 
Welters:   Der  IJaeillus  lepra?  (zusammenfassender  Bericht).     Cbl.  f.  Bakt.,  xiii.,  1893. 

See  also  the  Mittheil.  u.  Verhandl.  d.  Lepraconferenz,  Berlin,  1897;  and  the  Zeitschr. 
"  Lepra,"  edited  by  von  Ehlers,  appearing  since  1900,  in  Leipzig. 

§  174.  The  Bacillus  mallei  is  a  bacillus  discovered  by  Loffler,  Schiitz, 
and  Israel  in  ^laiiders  loci,  and  later  confirmed  and  studied  by  Weich- 
selbanni,  Kitt,  and  otliers.  It  istobe  regarded  as  tbecause  of  glanders 
(iiKi/lf'm,  }iiaJi((sini(.s)  and  of  fare;/  (sJihi  c/landers,  maUrits  farciminosus), 
a  contagions  disease  of  liorses,  which  occurs  in  man  chiefly  through 
transmission  from  horses. 


Cil.A.NDKHS. 


655 


The  glanders  bacilli  are  very  small,  slender  rods,  wliidi  (mtiii-  in  tli*- 
diseased  foci,  sometimes  scattered,  sometimes  lyini;  lo-ctlier  in  smull 
clumps.  Alkaline  methylene-blne  or  genlinn-violcl  is  ciiiploycd  es- 
pecially for  tlieir  stainins.-;. 

The  bacilli  are  present  chielly  in  Iheglandt'i-s-foci.  ImiI  ;iI  I  imrsai»pr:ir 
iu  tlie  blood  of  the  atfected  individnal  (LiilllU'r,  Kilt ). 

The  bacilli  gro\v  at  a  temperatnre  of  ;>()°-40"  V.,  npon  (-((aunlalccl 
blood-serum,  as  well  as  upon  slices  of  boiled  ])ot:ito,  and  upon  potato- 
pap.  Upon  the  latter  they  form  andu'r-yellow  coatings  that  later  be- 
come red.  Upon  blood-serum  they  form  small  yellowish  transparent 
drops  which  later  become  milky  white,  irpon  agar  the  colon i«'s  are 
grayish-white.  In  cultures  club-shaped  forms  and  threads  are  not  infre- 
quently seen.     Spore-formation  has  not  been  demonstrated. 

Horses,  asses,  sheep,  young  dogs,  goats,  cats,  guinea-i)igs,  and  held- 
mice  are  suitable  for  inoculation.  In  cats,  after  inoculation,  there 
develop  iu  the  testicles  cellular  foci  consisting  essentially  of  leucocytes 


W^^S^^^'^-^'^^^^S^^^iM^^^^'^ 


Fig. 


114.— Glanders  of  a  cat's  testicle  (Muller's  fluid,  hicinatoxylin).    a,  Seminlffroiis  liiinilfs;    l>, 
tubules  filled  with  leucocytes ;  d,  foci  of  leucocytes  in  the  connective  tissue,    x  iW. 


(Fig.  504),  which  lie  partly  inside  tlie  canalicnli  (/>,  c)  and  i)artly  around 
them  (d).  The  injection  of  the  pus  of  glanders  into  the  jx-ritoneal  ca\  - 
ity  of  male  guinea-pigs  causes  the  testicles  to  swell  rapidly  (Straus). 
After  subcutaneous  inoculafions  ulcers  (h'velop  at  the  seat  of  inoctda- 
tion,  followed  by  swelling  of  the  neighboiing  lymph-glands.  bat<'r,  jio<1 
ules  may  develop  in  the  internal  organs,  anci  ulcers  may  be  formed  in 
the  nose.  Typical  glanders  may  be  ])rodiiced  in  hors«'saiid  asses.  Cattle, 
white  mice,  and  house-mice  are  immune. 

The  usual  atrium  of  infection  in  horses  is  the  mnc(»ns  memlnaiie  of 
the  nose;  following  this  is  the  involvement  of  tin'  suhmaxillary  glands. 
and  further  a  metastasis  in  various  organs.     In  the  nasal  mncosji  there 


656  THE    PATHOGENIC    FISSIOX-FUNGI. 

arise  as  the  result  of  the  infection  either  diffuse  oelluhir  infiltrations  of 
the  mucosa  or  subepithelial  nodules  of  the  size  of  a  millet-seed  or  a  pea. 
In  chronic  farcy  of  the  skin  larger  nodules  are  developed  which  join  to- 
gether in  rows,  forming  worm-like  cords. 

The  uodules  of  the  mucous  membrane  break  down  easily.  The  cells 
of  which  they  are  composed  bear  for  the  greater  pait  the  character  of  pus- 
c()rj)uscles.  Tlirough  the  disintegration,  softening,  and  suijpuration  of 
the  nodules  ulcers  with  yellowish  infiltrated  bases  are  formed.  These  en- 
large through  a  pi-ogressive,  nodular  or  more  diffuse  infiltration  and 
subsequent  disintegratiou  of  the  edges  of  the  ulcer,  as  well  as  through  the 
confluence  of  neighboring  ulcers.  Horses  dying  of  glanders  often  present 
in  the  mucosa  of  the  nasal  septum  very  extensive  irregularly  shaped, 
sinuate  ulcers,  with  eroded  edges  and  floors  covered  with  gray  and  yel- 
lowish material.  In  addirion  to  these  there  are  numerous  small,  lenticu- 
lar ulcerations  and  gray  or  yellowish  nodular  foci  which  are  on  the  point 
of  breaking  down.  The  whole  process  is  closely  related  to  jiurulent  in- 
flammation. The  healing  of  the  ulcer  is  characterized  by  the  formation 
of  radiating  scars. 

The  cervical  lymph-glands  are  constantly  swollen  and  inflamed.  Of 
the  internal  organs  the  lungs  especially  are  involved.  They  contain 
either  nodules  having  a  caseated  and  disintegrated  centre  and  a  gi-ayish 
cellular  periphery,  or  foci  of  lobular  pneumouia,  which  present  either  a 
clear  gray  or  a  more  hsemorrhagic  appeai^ance,  or  through  fatty  and 
cheesy  metamorphosis  become  opaque  and  yellowish- white.  Occasionally 
the  mucosa  of  the  alimentary  tract  contains  nodules  of  varying  size,  in 
part  clear  gray  and  consisting  of  cellular  tissue,  in  x^art  opaque  yellow- 
ish-white, undergoing  caseation  or  approaching  suppuration.  The 
spleen,  liver,  kidneys,  and  bone-marrow  may  also  contain  nodules. 

In  farcy,  M'hich  runs  a  more  chronic  course  than  glanders,  there  are 
formed  in  the  skin  and  muscles  nodules  consisting  of  a  small-celled  tissue 
which  later  undergoes  retrogressive  metamorphoses,  caseates  and  disin- 
tegrates. 

In  man  an  infection  with  glanders  takes  place  usually  through 
small  wounds  of  the  skin,  but  may  also  occur  primarily  in  the  mucous 
inembranes  adjacent  to  the  skin.  In  the  skin  and  subcutaneous  tissue  it 
gives  rise  to  roseolar  spots,  Inemorrhages,  and  pai)ular,  nodular,  and  pus- 
tular exantliemata,  caibuncular  and  phlegmonous  inflammations  which 
may  result  in  suppuration,  and  to  i^urulent  inflammations  of  the  lymph- 
vessels  and  lymph-glands.  In  the  mucosa  of  the  respiratory  tract 
catarrhs  are  produced  and  suppurating  nodules  and  nodes  are  formed, 
leaving  ulcers  behind.  In  the  internal  organs  metastatic  small-celled 
nodules  are  formed,  showing  a  tendency  to  sup]niration ;  also  extensive 
abscesses  and  purulent  infiltrations,  especially  in  the  muscles.  In  chronic 
farcy  which  may  last  for  years,  huge  nodules  are  occasionally  formed  in 
the  skin  and  muscles  which  through  disintegration  give  rise  to  ulcers 
which  heal  witli  difficulty.  For  the  diagnosis  of  the  condition  the  bac- 
teriological examination  and  inoculation  experiments  are  necessary. 

According  to  the  investigations  of  Kalninr/,  Preusse,  and  others,  an  active  ])oisou, 
■iiKtUein,  may  be  extracted  from  cultnres  of  glanders  bacilli,  which,  Avhcn  injected  ia 
small  doses  into  horses  sick  of  glanders,  causes  afebrile  rise  of  temperature,  and  may 
b(^  used  as  a  diagnostic  aid. 


KINXOSCLEHOMV.  (i.")7 

Literature. 

{(ihtiKlrrs    and    l/ir    (ihlii<li  is-lxicili lis.) 

Babes:  Observations  sur  la  morve      Ardi.  do  med.  cxp..  iii.,  ISUl.     Ann.  do  I'lnst.  de 

patli.  de  Boucarest,  li.,  1893,  vi.,  189S;  Bckanipfunc;  d.  Hotzes.    Z.  f.  Ilvir.,  ."iit  lid.. 

1902. 
V   Earacz:  Cliron.  Rotz  beim  Menschen.     Virch.  Arcli..  ].")9  Hd..  ]!)()(l. 
Bass:   Die  Rotzkrankheit  der  Pferde.     Dent.  Zeitschr.  f.  Tliionni-d..  \ix..  I.s9;?  (Lit.). 
Baumgarten :  Znr  Frage  der  Sporenbildiiiii:  Ihm  Rotzhacillcn.     ("hi.  f.  Hakt.,  iii..  1S8S. 
Bardoui-UfiPreduzzi :  Ueber  die  Kultur  derKotzhacillen.     Zcitsclir.  f.  llvj:.,  iii.,   1S8K. 
Buschke;  Cliroii.  Kotz  d.  Haut  d.  .Menselu-ii.     Arch.  f.  Derm..  M\  Hd..  i.S9(). 
Cadeae  et  Malet:  Et.  exper.  de  la  transmission  de  la  morve.     Rev.  de  m(-<|..  vii..  1S.S7. 
Coleman  and  Ewing-:  Septicjcmic  Glanders  in  tiie  Human  Subject.     Jour,  of  .Med. 

Pa-..  19U:;. 
Duval-  Morve  humaine.     Arch,  de  mcd.  exp.,  1896. 
Eber:  Ueber  Rotzlymphe  (Mallein).     Cbl.  f.  Bakt..  xi.,    lS9-_'. 
Ehrich:  Rotz  beim  Menschen.     Beitr.  v.  Bruns.  xvii.,  189(1. 
Finger:  Ziir  Frage  der  Immunitat  u.  der  Phasjocvtose  beim  Rotz.     Beitr.  v.  Zitglcr, 

vi..  1889. 
Foth:   Das  Mallein.     Fortschr.  d.  Med.,  xiii.,  1895. 
Froth  in  gham :  The  Diagnosis  of  Glanders  by  the  Straus  Metho.l.     .lour,  of  .Mcd.  Res., 

l.tul. 
Galli-Valerio:  La  morphologic  du  B.  mallei.     Cbl.  f.  Bakt..  xxviii..  19(10. 
Jakowski:  (^'hron.  Rotz  beim  Menschen.     Zeitschr.  f.  klin.  .Med.,  xvii..  1.S91. 
Johne;   Mallcin-Rotzimpfungen  bei  Pferden.     Deut.  Zeitschr.  f.  Thiermed..  xix.,  189."?. 
V.  Kahlden:  Rotz.     Eulenburg's  Realencyklop..  xx.,  1899  (Lit.). 
Kernig:  lun  Fall  v.  chronischem  Rotz  beim  Pfenle.     Zeitschr.  f.  klin.  Med.,  xiii.,  1S87. 
Kitt:  Impfrotz  bei  Waldmausen.     Cbl.  f.  Bakt..  ii.,  1887. 
Kiittner:  Rotz  beim  Menschen.     Virch.  Arch.,  39  Bd..  1867. 
Leclainche  et  Montane:  Anat.  Path,  de  la  morve  pulmonairc.     Arch,  de  lln-t.  P., 

vii.,  1893. 
LofBer:  Die  Aetiologie  der  Rotzkrankheit.     Arb.  a.  d.  Kais.Ge.sundheitsamte,  i.,  1880. 
IffiacCalluni :  Hamatogener  Limgenrotz.     B.  v.  Ziegler,  xxxi.,  1903. 
Btarx:  Morphologie  d.  Rotzbacillus.     Cbl.  f.  Bakt..  xxv..  1899. 
Mayer:  Rotzbacillus  u.  Rotzknotchen.     Cbl.  f.  Bakt.,  xxvii.,  1900. 
Pflug:  Zur  pathol.  Zootomie  d.  Lungenrotzes,  Leipzig,  1877. 
Remy:  Morve  chronique  de  Thomme.     Arch,  de  med.  exp.,  ix..  1897. 
Straus:  Es.sais  de  vaccination  contre  la  morve.     Arcli.  de  mcd.  exp..  i.,  1889. 
Tedeschi:  Rotzmeningitis.     Virch.  Arch.,  130  Bd.,  1892;    Wirkungd.  Einimpfuug  d 

Pvotzes  in  die  Xervencentra.     Beitr.  v.  Ziegler,  xiii.,  1893. 
Wladimirofif:  Rotz.     Handb.  d.  pathog.  Mikroorg..  ii.,  Jena,  1903  (Lit.), 
Zieler:  Cliron.  Rotz  beim  Menschen.     Z.  f.  Hyg.,  4.3  Bd.,  1903. 

§175.  As  the  Bacillus  of  rhinoscleroma,  I'liscli,  rclli/.:iri.  Cliiaii, 
Cornil,  Alvarez,  KoV)iier,  raltanr,  voii  KiselslM-fii",  Ditlridi,  aiidntlieis 
have  de.scribed  •ibacilhis  willi  loiiiided  ends,  wliieli  is  eonslaully  present 
in  the  diseased  condition  known  as  rliiiiosrUroina  or  .srlnoiini  nsjnni- 
torium  (Bornhaupt,  Wolkowitseh),  and  is  therefore  re}j:arded  as  tln' cause 
of  the  same.  It  stains  best  Mitli  methyl-violet,  the  sections  Ixdnj;  jelt  in 
the  stain  for  twenty-fonr  to  forty-eight  liours.  After  staining,  tlie  .sec- 
tions are  treated  witli  iodine  water,  or  left  in  absolute  alcoliol  for  one  to 
three  days.  The  bacilli,  for  the  greater  part,  po.ssess  a  liyaline  capsule 
and  are  closely  relate*!  to  the  ])neunionia-baciIlus  (J^  1«>(!). 

Rhinoscleroma  occnis  chietly  in  eastern  Austria  and  s()uth\v«'slern 
Russia;  i.solatcd  cases  have  been  observed  also  in  Silesia.  Italy,  Egypt. 
Belgium,  Sweden,  Switzerland,  and  Central  America.  It  is  a  clmuiic 
disease  progressing  for  yeais,  beginning  in  the  n(»se  (  Wolkowit.sch  ),  more 
rarely  in  the  pharynx,  larynx,  or  palate,  and  extending  theiic*'  to  neigh- 
boring parts— the  external  nose,  liji.s,  laciiiN  inal  duct,  tradira.  df.  In 
42 


658 


THE    PATHOGENIC    FIfeSIOX-FUNGI. 


the  nose  the  disease  is  characterized  by  a  thickening  of  the  nasal  wall 
which  is  sometimes  diffnse,  sometimes  elevated  or  nodular.  The  exter- 
nal skin  takes  on  a  red  or  brownish-red  color,  becomes  stiif  and  fissured 
and  covered  with  scales.  In  the  throat  and  respiratory  tract  dense,  car- 
tilage-like infiltrations  are  sometimes  present,  at  other  times  a  contract- 
ing cicatricial  tissue  is  formed.  The  infiltrations  may  appear  in  the 
form  of  nodes  and  nodules  or  as  elevations  and  flattened  areas  of 
thickening,  or  they  may  be  spread  out  more  diffusely.  By  the  transfor- 
mation of  the  infiltration  into  scar  tissue  marked  deformities  of  the 


^M 


Fig.  505.— Section  of  rhinoscleromatous  tissue,  with  numerous  degenerated  and  vacuolated  cells  contain- 
ing bacilli  (osmic  acid,  hasmatoxylin).    Preparation  by  Stepanow.    X  340. 

Fig.  506.— Cells  in  condition  of  hyaline  degeneration,  and  hyaline  spherules,  from  rhinoscleromatous 
tissue  of  the  vocal  cord  and  of  the  nose.  Preparation  by  Stepanow.  a,  ft,  c,  d.  Hyaline-degenerated  cells 
containing  small  bacilli;  c.  hyaline  cells  with  encapsulated  bacilli;  /,  </,  cells  with  hyaline  spherules;  h, 
free  hyaline  spherules,  a,  ft,  c,  if.  Stained  with  Loffler's  solution ;  e,  with  haematoxylin  ;  /,  cr,  /i,  with  fuch- 
sia.   X  425. 

affected  organs  may  be  produced.  Deep  destruction  of  the  tissues  is 
absent ;  superficial  ulcerations  may,  however,  occur.  On  section  the  infil- 
trated tissue  appears  yellowish,  spotted,  but  not  infrequently  shows  a 
gray  or  grayish-red  color.  The  tissue  of  the  affected  areas  consists  partly 
of  granulation  tissae,  partly  of  fibrous  connective  tissue.  If  the  former! 
extends  to  the  epithelial  covering  there  appear  in  part  proliferations,  iuf 
part  degenerative  processes  in  the  epithelial  cells,  the  latter  being  char- 
acterized by  the  formation  of  vacuoles  and  by  an  infiltration  of  the  part^ 
with  round  cells.  According  to  Stepanow  the  vacuoles  may  contain 
bacilli. 

The  granulation  tissue  itself  shows  in  many  places  no  especial  pecu 
liarities;  rather  does  it  present  the  same  conditions  present  in  other] 
inflammatory  infiltrations  and  proliferations  of  connective  tissue.  In 
other  i)laces,  on  the  contrary,  there  may  be  found  a  larger  or  smaller 
number  of  large  connective-tissue  cells  containing  one  vacuole  or  show 
ing  a  total  vacuolar  degeneration  or  a  reticulated  structure,  in  the  meshef 
of  which  bacilli  may  be  demonstrated  (Fig.  505),  some  of  the  latter  j)OS- 
sessing  capsules. 

Besides  the  cells  showing  vacuolar  degeneration  there  also  occnr  celh 
of  various  shapes  which  ha\e  undergone  hyaline  change  (Fig.  506,  a,  b. 
c,  d,  e).  These  also  contain  bacilli  with  and  without  capsules,  and  also 
coccus-like  forms.  Through  the  loss  of  their  nuclei  these  cells  may  be 
come  converted  into  non- nucleated  homogeneous  lumps  {(I).  Finally 
there  also  occur  cells  which  enclose  hyaline  splierules  (f,  //),  and  fre^ 
spherules  are  also  found  lying  in  the  tissues  (/;).     In  places  not  yet  afj    gT 


RHINOSCLKHOMA.  050 

feotcil  by  cicaliicial  rctro^nivssioii  tlic  liyaliii.'  Idiiiiat  ions  may  br  picsciit 
in  large  mimbrrs. 

According  to  ralfaiif,  von  Etschho-fj,  DiUrirh,  Wdlloirlturh,  und  ollicrs,  llic  Imrilli 
pf  rhiuoscleroiiia  may  be  cultivated  iipon  biood-senim,  gclutin,  agar-agnr,  and  pota- 
toes, and  also  form  capsules  in  tiie  cultures.  Wlien  grown  in  bouillon' tiicy  show  on 
the  contrary  no  capsules  {Diitvich).  Stab-cultures  in's-clatin  rescnibl(!  closely  the  nail- 
cultures  of  the  Friedliuuler  i)neumonia-bacillus.  but  are  of  a  translucent  graVish-whitt; 
and  not  dead  white.  The  bacilli  stain  more  easily  tlian  tii(!  ])neunionia  l)aeill"i,  and  al.so 
stain  by  Gram's  method,  t'tepanow  observed,  in' inoculations  into  the  eyes  of  guinea- 
pigs,  progressive  iutlammations  and  proliferating  granulations  containing  the  bacilli 
and  hyaline  degenerated  cells. 


Literature. 

{Tiltimm-hroiHU.) 

Alvarez:  Recherches  sur  I'anatoniie  patliol.  du  rhinosclerome.     Arch,  do  pliys.,  vii. 

ISSG. 
Babes:  Rhiuosklerom.     Handb.  d.  path.  Mikroorg.,  iii.,  Jena,  1903  (Lit.). 
Bender:  Das  Rhinoslderom.     Cbl.  f.  Bakt.,  i.,  1SS7. 
Chiari:  Stenose  des  Kehlkopfes  u.  des  Larvux  l)ei  Uhinosklcroni.     \\ien.  med.  Jalirb., 

1SS2. 
Cornil  et  Alvarez:  Mem.  p.  serv.  a  I'hi^t.  (hi   rliinosclerome.     Arch,  de    phvs.,  vi., 

ISSo. 
Dittrich:  Ueber  das  Rhiuosklerom.     Zeitsehr.  f.  Ileilk.,  viii.,   1SS7;    Zur   Aetioh)gie 

des  Rhinoskleroms.     Cbl.  f.  Bakt.,  v.,  1889;    Zeitsehr.  f.  lleilk.,  viii. 
Frisch:  Zur  Aetiolologie  des  Rhinoskleroms.     Wien.  med.  Woch.,  1SS2. 
Jaffinger:  Das  Sklerom  d.  Schleimhaut  d.  Nase,  etc.,  Wien,  1S9'_'. 
Konstantinowitsch:  Entstehung  cler  hvahnen  Korperchcn.     Virch.  Arch.,  107  Bd., 

19()L*. 
V.  Marschalko:  ULstologie  des    Rhinoskleroms.     Arch.    f.    Dcrmatnl.,    .">;>,    ^4    Bii., 

1900. 
Mibelli:  Beitrag  zur  Hist ologie  des  Rhinoskleroms.     Monatsii.   f.  prakt.    Derm.,   viii., 

1889. 
Mikulicz:  Ueber  das  Rhinosklerom.     Langenbeck's  Arch.,  20  Bd.,  187(5. 
Nikiforoff:  Ueber  das  Rhinosklerom.     Arch.  f.  exp.  Path..  .\.\iv.,  1888. 
Paltauf:  Aetiolosie  des  Skleroms.     Wien.  med.  Woch.,  1891,  1892. 
Paltaufu.v.  Eiselsberg:  Zur  Aetiologie  des  Rhinoskleroms.     Fortscluitte  d.  Metl., 

188(). 
Pawlowsky:  Ueb.  d.  Aetiologie  des  Rliinoskleroms.     Cbl.  f.  allg.  Path.,  i..  j).  001. 
Pellizari:   il  Rhinoskleroma,  I'irenze,  1883. 

Bona:  Rhinosklerom.     Arch.  f.  Derm.,  49  Bd.,  1899,  u.  58  Bd.,  1901. 
Stepanow:  Ueber  die  Impfungen  des  Rhinoskleroms.     Cbl.  f.  liakt.,  v.,   1S89;    Zur 

Aetioloejie  des  Skleroms.     Monatssehr.  f.  Ohrenheilk.,  1893. 
Wolkowitsch:  Das  Rhinosklerom.     Langenbeck's  Arch..  38  Bd.,  1889. 
Zagari:  Rieerelie  etiol.  sul  Riuoseleroma."    (liorn.  internaz.  d.  Se.  .Med.,  1889, 

§  176.  Tlie  Actinomyces  or  ray-fungus  is  ;i  ijolyinorplious  fis-sioii- 
fuiigus  whieli  appears  ill  (lillVrciit  loriiis  of  growlli  in  tlie  lniiiiaii  and 
animal  organism  as  Avell  as  in  cultures.  It  is  the  cause  of  actinomycosis, 
a  disease  occurring  in  man  as  well  as  in  callle,  swine,  and  iiorses,  nmie 
rarely  in  sheep,  dogs,  and  cats,  and  chaiacterized  by  a  i)rogressive  inllani 
mation  that  produces  in  part  granulation  tissue  and  connective  ti.ssue, 
and  in  part  i)us.  The  botanical  ]>osilion  of  tlie  fungus  is  still  unsettled. 
By  many  it  is  classed  with  the /A/Yw/-./"»///,  others  grouj)  il  with  the  /)o///- 
morphoiis  bacteria.  Bostrom  places  it  iu  the  group  cJailot/irir;  Kruse, 
i  11  the  group  streptoihrix. 


GGO 


THE    PATHOGENIC    FISSION-FUNGI. 


According  to  tlie  investigations  of  Bostroiu  actinomyces  differs  from 
the  bacilli  in  the  fact  that  in  cultures  ui3on  beefs-blood  serum  or  agar  it 
forms    branching/    threads.      The 

threads  of  the  cultures  are  partly  f^P^^^^^^^i^:^^^-^'^^^'"^ 

straight,   partly  wavy,  at  times  j-f  f^*^^^^^^^^^'^^^       ^* 

also     twisted     spirally.       They 
break  up  by  transverse  division 


Tig.  507. —  Act  hiomjiceshominis.     Teased  preparation.     X  700- 

Fig.  508.— Actinomycosis  of  the  tongue  (alcohol,  alum  carmine.)    a,  Actinomyces  druse;  7(,  (\  cellular 
nodules ;  d,  transverse  section  of  muscle ;  e,  /,  connective  tissue  with  blood-vessels.    X  l"'^. 

into  short  rods  and  coccus-like  forms,  which  under  suitable  conditions 
again  grow  into  threads. 

Within  the  human  and  animal  organism  the  fungus  appears  in  masses 
in  the  form  of  little  granules  scarcely  recognizable  by  the  naked  eye,  or 


"^a"^ 


J^ 


JM- 


:-^ 


e^"^-: 


%^M\ 


%..&'■  '-■«>■■*■ 


4^**^, 


<>•»*# 


o,  ,(„?'*''•  •^^•"■^'■'^'""•nvi  esdrusp,  surioundcd  hv  epithelioid  and  pus-corpuscles  (alcohol,  hiematoxylin, 
osin).  a,  FuriRus  diiise,  /»,  mononiuliMi  and  inultinucleai  ( pitlielioid  cells,  c,  pus-corpuscles :  (J, 
pn.i^ocyte,  euc  loMug  a  pus-toipuiHe  .  t,  jfiauuLition  tissue.     X  500. 


insi)heiules  uj)  to  '2  mm.  in  diameter.  These  are  sometimes  colorless: 
and  transparent,  at  other  times  Avhite  and  opaque,  sometimes  yellow,  ori 
bi-own,  or  green  and  yellowish-green.     Many  of  the  smaller  ones  consist 


ACTIXO.MYCOSIS. 


00] 


only  of  a  feltwork  of  fine,  i):utly  branclicd  tlireads,  some  of  vliich  nrr 
straiiiht,  or  wavy,  or  twisted.  Tlie  luajoiily  of  the  jiramiles  coiilaiii. 
iuortM)\er,  ])0('nliar  club-sliaped  slructiircs  (Fiji'.  507),  wliii'h  form  the 
ends  of  tlie  threads,  and  if  jnesent  in  lai'iie  luimlH'rs,  as  is  llie  ease  ]»ar- 
tieularly  in  the  hiruer  ui-annh-s,  ha\e  a  ladial  an'an<::ement  (l'i.u:s.  r>(»S.  n; 
rt09,  a),  and  so  give  to  llie  eohtny  of  llie  fununs  a  ray-like  appeaianec. 
Oeeasionally  liand  or  fan-like  forms  develoj)  on  tlie  ends  of  llie  threads. 
Aecoi-diny;  to  Bostr()m,  all  these  jieenliar  strnetures  are  {\\\i-  to  a  swcliinu- 


% 


Fig.  510.— Actinomycosis  of  the  lung  (akohol,  carmine.  Gram's),  a,  Fiiiifrus  dni.st';  '«.  small-ot'IIt'<l 
nodule;  c,  flbroiis  tissue;  d,  alveoli  Hlled  with  large  and  small  cells;  c,  bronchiole  with  wall  Inllltrateil 
with  cells ;  /,  small-celled  focus  in  the  neiffhborhoort  of  the  lironchus  (< ) :  (/,  ah  eoll  lllled  with  vnwularl/.ed 
connective  tissue;  /(.connective  tissue  growing  Into  the  alvcuii ;  i,  IiIcpimI-vcssi-Is  of  ilu-  lung  tlssm-; 
ft,  blood-vessels  of  the  inflamed  area.     •:  42. 

of  the  membrane  of  the  threads,  and  are  to  be  re<iarded  as  ictrojcre.ssivo 
changes. 

The  actinomyees  is  usually  taken  into  the  body  with  th.-  lood  or  the 
respired  air,  and  linds  its  first  th-\  elo]»ment  often  in  llie  montii.  The 
fungus  has  not  yet  been  demonstrated  outsidi'  of  the  human  and  ;inim:d 
organism.  It  inust  be  ivmaiked  that  very  often  bits  of  higher  j. hints 
(beard  of  wheat,  splinter  of  wood,  a  l)it  of  grass)  hav«'  bet'ii  found  in  the 
pus  of  actinomvcotic  foei,  and  that  tlie  swallowing  of  ])ortions  of  ])hints 
(spike  of  grain' [Bertha])  or  the  eontaminati(m  of  woiinds  with  veg»'talih' 
material,  have  in  certain  cases  preeeded  the  development  of  aetiniuny- 
cosis.  It  is,  therefore,  very  probable  tlmt  the  fungus  is  jueseiit  upon 
the  higher  plants  or  upon  wood.  Johiie  demonstrated  it  as  eaily  as 
1882  upon  beards  of  wheat  found  sticking  in  the  tonsils  <.f  swin.-.      Ac- 


662 


THE    PATHOGENIC    FISSION-FUNGI. 


cording  to  Bang-,  it  develops  also  upon  wheat  grains  and  straw.  If  beans, 
rye,  or  barley  is  grown  in  a  soil  infected  with  actinomyces  cultures 
(Liebmanu)  the  ray-fungus  may  be  found  later  in  vai-ious  x>ortions  of 
the  plants. 

If  the  ray -fungus  succeeds  in  settling  in  a  tissue  it  excites  au  inflam- 
mation in  its  neighborhood.  While  the  fungus  which  has  penetrated 
into  the  tissue  develops  a  mycelium  and  a  fungus-granule  (Figs.  508,  «; 
509,  a ;  510,  «)  there  is  formed  in  its  neighborhood  a  nodular  focus  of 
inflammation,  which  at  first  consists  of  leucocytes  (Figs.  508,  h,  c;  510, 
b);  but  later,  in  addition  to  i)US-corpuscles  (Fig.  509,  c),  also  contains 
epithelioid  cells  and  giant-cells  (h,  d). 

The  fungus-granules  may  increase  within  the  nodule  and  lead  to  its 
enlargement ;  and  it  very  often  happens  that  cellular  nodules  the  size  of 
a  pea  and  larger  contain  a  large  number  of  fungus-foci,  which  are  usually 

situated  in  the  perij^hery  of  the 
same.  At  the  same  time  new 
fungus-foci,  and  consequently  new 
cellular  foci,  may  appear  iu  the 
neighborhood.  The  further  spread 
of  the  infection  takes  place  by 
means  of  small  rods  and  threads, 
which  are  broken  off  from  the 
larger  masses,  and  may  be  seen  in 
the  tissues  partly  free  and  partly 
enclosed  iu  cells. 

Larger  nodules  often  undergo 
in  time  a  purulent  liquefaction  of 
their  central  i)ortions,  leading  to 
the  formation  of  small  abscesses, 
which  may  become  confluent  to 
form  larger  xms-cavities  or  sinuses. 
Iu  the  neighborhood  of  the  puru- 
lent areas  (Fig.  510)  there  develops 
early  an  active  jirolifemtion  of 
tissue,  which  leads  to  the  formation  of  vessels  (k)  and  young  f/ranutation 
tissue,  which  later  becomes  transformed  into  cicatricial  connective  tissue 
{c,  g,  h).  If  the  connective-tissue  proliferation  attains  very  considerable 
proportions,  it  leads  to  an  induration  (Fig.  510),  often  also  to  an  enlarge- 
ment of  the  tissue.  The  connective-tissue  j^roliferation  may  finally 
extend  into  the  small-celled  areas,  and  rex)lace  the  latter,  tiie  fungi 
probably  being  destroyed  in  this  way. 

A  predominance  of  tissue-necrosis  and  of  supimration  over  tissue-pro- 
duct ion  gives  rise  to  more  or  less  extensive  sinuous  cavities  and  branch- 
ing fistuk)us  tracts  communicating  with  one  another.     The  walls  of  these  ' 
consist  of  granulation-tissue  and  hyi^erplastic  connective  tissue,  and  here  i 
and  tliere  contain  fungus-foci.     The  masses  of  fungi  may  in  part  become  j 
calcified. 

In  cattle  the  disease  affects  chiefly  the  lower  jaAV,  but  may  involve  I 
also  the  upper  jaw  (Fig.  511,  a),  the  tongue,  throat,  larynx,  oesophagus,  | 
stomach,  intestinal  wall,  skin,  lungs,  andsubcutaneous  and  intermuscular  I 
tissues;  iu  swine  it  is  found  in  the  udder  and  different  bones  of  the  1 
skeleton,  while  in  //oy.sY.s- it  occurs  chiefly  in  the  vas  deferens  following' 
castration.  Iu  catth^  it  leads  to  the  formation  of  more  or  less  extensive 
fibrous  tumors  containing  purulent  foci,  and  was  formerly  given  various 


Fig.  511.— Frontal  section  through  the  nose  and 
upper  jaw  of  a  steer  affected  with  a  tumor-lilje 
actinomycosis,  a.  Nodules  consisting  of  connective 
tissue,  bone,  and  small  pus  foci.  One-fourth  nat- 
ural size. 


ACTi  x  o.M  vc'(  )si  s.  (i(  i:i 

nanios,  such  as  ostoosarcoina,  boiio-eaiu'cr,  Ixtnc-lulxMculosis,  lumpy  jaw, 
wooden  tiMiiiue,  tuberculosis  of  tlie  tonj^ue,  lyniplntnia,  Jil)ronia,  wonii- 
nodules,  ete. 

In  mail  the  infectiou,  so  far  as  is  known,  takes  ])laee  11n()u<,'li  llic 
mouth,  fauces,  oesophagus,  stomach,  intestine,  and  hing,  or  througii  some 
external  injury.  In  the  first-named  region  an  infection  of  actinomyees 
may  take  its  start  from  carious  teeth  (cavities  or  tistula').  or  front  any 
injury  to  the  soft  parts  of  tlie  jaw  or  check.  Tiicncc^  it  s])reads  over  tlie 
neighborhood  and  may  finally  involve  the  face  and  the  hairy  ]»ortions  of 
the  head,  as  well  as  the  throat,  neck,  back,  and  iireast. 

With  the  advent  of  the  ])rocess  there  arise  swellings  which  hiler 
soften  and  give  fluctuation.  When  the  latter  is  the  case,  ))us  is  formed 
which  is  at  times  thin  and  wjitery,  at  other  times  more  viscid,  and  con- 
tains the  characteristic  granules.  If  these  abscesses  break  exleina  I  ly  tlier«' 
may  be  formed  fistulous  tracts,  which  may  either  close  again,  oi-  continue 
to  secrete  pus. 

Besides  these  purulent  foci,  which  sometimes  are  small,  at  other  times 
extensive,  there  is  constantly  formed  nu)re  or  less  granulation  tissue, 
which  at  times  may  be  very  abundant.  As  a  result  of  fatty  degeneiation 
and  disintegration  of  its  elements  the  granulation  tissue  often  becomes 
partially  whitish  or  yellowish  or  reddisli-white  in  coloi-,  and  peiineates 
the  diseased  tissue  iu  an  irregular  manner.  In  other  places  it  comes  to 
a  development  of  connective  tissue,  particularly  in  those  jilaces  where 
the  process  is  not  spreading. 

Through  this  development  of  connective  tissue  a  local  healing  icsult 
ingin  cicatricial  indurations  may  take  place,  but  inotlu'i'  ])arts  the  piocess 
usually  makes  further  progress  and  may  under  certain  cii-cumstances  lead 
to  very  extensive  destruction.  If  the  disease  encroaches  upon  the  bones 
of  the  spinal  column  or  of  the  thorax  these  may  l>e  gradually  destroyed 
from  the  surface,  and  become  rough,  eroded,  and  carious.  In  raic  cases 
the  jaw-bone  may  be  attacked  from  within  thi-ongh  an  alveolar  ])ro<-ess, 
and  so  undergo  destruction.  From  the  base  of  the  skull  the  pi-ocess  may 
extend  into  the  interior  of  the  skull  and  lead  to  actinomycotic  meningitis 
and  encephalitis. 

In  primary  infection  of  the  respiratoiy  api)ai:i1ns  tin'  process  takes 
the  form  of  a  bronchopneumonia  characterized  by  llie  formation  of  nod- 
ular foci  (Fig.  510,  b)  the  central  portions  of  which  at  an  early  stage 
assume  a  yellowish-white  color.  Through  the  disintegration  of  the  in- 
flammatory foci  cavities  may  l»e  formed  which  contain  lluid,  jtus corpus- 
cles, fatty  detritus,  spherules  of  fatty  granules,  disintegrated  i-ed  cells, 
and  masses  of  actinomyees.  The  tissue  lying  lu'tween  th«' my<*olic  foci 
suffers  a  more  or  less  extensive,  often  verymaiked.  inflammatory  thicken- 
ing and  induration  (Fig.  510,  c),  and  tlirough  a  new  I'ornnition  of  con 
nective  tissue  nuiy  be  transformed  into  a  callous,  slate  gray  oi-  giay  and 
white  mass,  devoid  of  air,  and  later  undergoing  cicati-icia!  contraction. 
In  this  manner  a  large  portion  of  the  lung  may  l)ecom«'  conveiled  into  a 
mass  of  connective  tissue. 

From  the  lung  the  process  sooner  or  latei-  extends  to  tlie  visceial 
pleura,  and  from  this  to  the  costal  pleura  or  to  the  peiicardium,  giving 
rise  in  these  places  to  inflammatoi-y  exudations  and  i»i<>literalions  of  tis- 
sue, which  may  lead  to  adhesions  between  tlie  opposite  layers  of  the 
pleura  or  pericardium.  Frcmi  the  costal  i)lenra  the  cellular  inlillratioii 
•as  well  as  the  pus  formation  and  the  fatty  degeneration  and  disintegra- 


664  THE    PATHOGEXIC    FISSIOX-FUXGI. 

tion  of  the  jirannlation  tissue  may  extend  between  the  ribs  to  the  out- 
side, and  spread  in  the  contignons  soft  parts,  in  the  connective  tissue 
and  muscles,  and  may  tinally  break  through  in  places.  From  the 
lungs  a  rupture  may  sometimes  take  place  into  the  mediastinum  or 
pericardial  sac,  and  tinally  into  the  heart.  Under  certain  conditions  a 
rupture  may  occur  through  the  diaphragm  into  the  abdominal  cavity,  ( ti- 
the process  may  extend  from  the  posterior  mediastinum  into  the  retro- 
peritoneal connective  tissue. 

The  secondary  areas  of  destruction  lying  outside  of  the  lung  often 
reach  an  extremely  large  size,  while  in  the  lung  the  primary  process 
advances  but  little  and  undergoes  cicatrization.  At  one  time  the  puru- 
lent softening  predominates,  at  another  time  the  formation  of  granulation 
tissue  and  the  induration. 

Primary  actinomycosis  of  the  intestinal  tract  begins  with  the  forma- 
tion of  plaque-shaped  whitish  patches  of  the  fungus  (Chiari)  or  of  nodu- 
lar mucosal  and  submucosal  foci  (Zemann),  which  contain  the  specific 
fungus,  and  lead  to  ulceration  through  the  occurrence  of  disintegration. 
From  the  intestine  the  process  spreads  over  the  peritoneum  and  the  retro- 
peritoneal connective  tissue,  as  well  as  to  the  organs  adjacent  to  the  pri- 
mary focus — for  example,  the  liver;  and  may  finally  break  through  the 
abdominal  wall. 

Metastasis  may  be  associated  with  tlie  local  progression  of  the  disease, 
but  is  rather  rare.  It  usually  results  from  a  direct  rupture  into  a  blotxi 
vessel.  The  metastases  arising  from  a  primary  focus  in  the  intestine  ar»' 
found  especially  in  the  liver;  those  arising  from  a  primary  focus  in  the 
lungs  are  found  in  the  skin,  muscles,  bones,  brain,  intestine,  and  kidneys. 
The  metastatic  nodules  behave  like  the  primary  foci.  In  rare  cases  theie 
occur  also  primary  foci  of  actinomycosis  in  the  internal  organs — for  ex- 
ample, in  the  brain  and  liver.  The  portal  of  entrance  in  these  cases  ma> 
not  be  demonstrable. 

Johne,  Ponfick,  Bostrom,  Wolff,  and  Israel  have  attempted  inocula 
tion  experiments  upon  animals,  and  according  to  their  reports  have 
obtained  positive  results  in  part  (Johne,  Ponfick,  Wolff,  and  Israel  K 
Wolff  and  Israel,  by  the  inoculation  of  rabbits  and  guinea-pigs,  obtained 
in  almost  all  cases  a  characteristic  disease  with  the  formation  of  intlani- 
matory  foci  containing  the  fungus-masses.  They  were  also  able  again  to 
cultivate  upon  agar-agar  the  fungus  contained  within  these  foci. 

Levy,  as  weU  as  Kruxe,  assumes  that  there  are  two  forms  of  actinomyces,  an  aercliir 
cultivated  by  Bostrom,  and  an  anaerobic  cuhivated  by  Wolff,  Israel,  Aschoff,  and  liimscl!. 
the  two  forms  being  closely  related.  Merte?}s  annomices  that  he  has  succeeded  in 
changing  the  Wolff-Israel  form  into  the  Bostrom.  Levy  regards  the  actinomyces  as  well 
as  the  fine-threaded  fungus  known  as  streptothrix  as  belonging  to  a  group,  the  Hyphotny- 
cetes,  characterized  by  Uie  formation  of  branching,  probably  unicellular  mycelia  and 
which  multiplies  through  an  acrogenic  snaring-off  ofconidia-chains  or  through  fragments 
of  threads  resembling  bacilli.  Since  the  ray-fungi  do  not  correspond  to  any  one  of  the 
known  hyphomycetes-groups,  he  places  them  in  a  separate  gi-oup,  the  Actiiiomycetes. 
In  this  group  he  also  places  the  tubercle-bacillus,  the  lepra-bacillus,  the  diphtherin- 
bacillus,  and  the  bacillus  of  glanders.  Lubarsch  regards  the  streptothrices,  with  wliich 
he  classes  the  ray-fungi  (to  which  the  tubercle-bacillus  also  belongs),  as  a  transition  form 
between  the  bacilli  and  the  moulds. 

i^eres^new  also  distinguishes  different  forms  of  actinomyces  (cultivated  by  him  from 
straw,  hay,  etc.),  and,  in  addition  to  actinomycosis,  recognizes  a  condition  of  pseiahi- 
actinomycosis,  which  runs  a  similar  course  to  that  of  the  former,  but  is  caused  by  fungi 
which  do  not  belong  to  the  ray-fungi.  Kranse  and  Gilbert  likewise  regard  the  etiological 
factor  of  an  actinomycosis  as  being  of  varied  nature  and  not  rejjresenting  a  definite  entity. 
Schiirmayer  emphasizes  the  variabilitj^  of  actinomyces  according  to  the  conditions  of 
gi-owth.     Wright  believes  that   human  and   bovine  actinomycosis  are  identical,  and 


THICHOMYCKTKS.  (i(l5 

further  holds  that  there  is  hut  one  species  of  iiiieroorganism  (Artimnni/ns  hin-is)  cdii- 
coriied  in  tii(>  protiuctiou  of  tyjiieal  aetiiioniyi-osis.  'I'lie  lesions  jjrodueed  i)y  other  forms 
of  braiu'hiuii  organisms  he  would  elass  under  the  h(>ad  of  tKicdnliosi.'^,  reservini;  the  term 
actinomycosis  for  those  eomlitions  in  whieii  ciiaraeterislie  "  drusen  "  are  formed. 

According  to  Dunkcr  {Zcitschr.  f.  M ikroskoplc  utul  Fhischftcluni.  iii.,  ISSl )  ami  Ilcrl- 
n'ig  (Arch.  /.  iri.'<sensch.  u.  prakt.  Thicrhcilk..  xii..  ISSd)  there  occurs  in  h<i(js  a  rdiz-funtjiis 
which  is  always  situated  in  the  nuiscles,  partic\ilarly  in  the  diaphragm,  abdominal  and 
intercostal  muscles,  and  causes  a  degeneration  of  the  muscle-fit)res  in  its  neighborhood 
and  proliferation  of  the  intennuseular  connective  tissue.  The  funirus-masses  form 
radially  arranged  clubs.  They  readily  midergo  ealcitication  and  ilnii  form  wliilu 
jxiints  in  the  flesh. 

Pctruschky  unites  Actinomyces.  Stre])tolhri\.  Cladotiu-ix,  and  Li'i)tothrix  into  one 
family,  which  he  calls  the  Hair' fungi  or  Trichomycetes.  These  he  cla.s.ses  also  with 
tlie  hyphomycetes,  of  which  he  distinguisiies  two  great  classes,  the  mould  fungi  and  the 
hair  fvmgi. 

Actinomyces  is  characterized  by  radiating  forms;  Ktreptothris  by  true  branching, 
late  fragmentation  of  the  wavy  threads  and  the  formation  of  conidia;  cladnthrix  by 
false  branching  of  the  threads  (a  lateral  direction  of  the  membrane  with  a  continuation 
of  the  longitudinal  growth  in  the  other  direction)  and  rajiid  fragmentation  of  the  threads; 
while  Icptuthn'x  is  characterized  by  .stiff  threads  without  branching. 

There  occur  numerous  observations  in  whicli  organisms  ai),irt  from  the  actinomyces 
described  above  and  belonging  to  the  trichomycetes,  particularly  to  t\\r  strr/itdthrices, 
gave  rise  to  local  tissue-changes,  particularly  purulent  and  granulating  inllannnations, 
and  in  part  also  to  tubercle-like  changes,  but  in  many  cases  the  authors  have  not  agreed 
as  to  what  species  the  fungus  concerned  belonged. 

As  early  as  1855  fungus  masses  were  ob.served  by  von  Graeje  in  the  inflamed  lach- 
rymal duct.  The.se  were  at  first  regarded  as  favus,  but  later  Cohn  (1S74)  regarded  them 
as  streptothrix  and  gave  them  the  name  of  Streptothrix  foerstcri.  Likewise  Axenfcid, 
who  has  many  times  cultivated  the  fungus,  regarded  it  as  a  variety  of  streptothrix. 

Under  the  term  Cladnthrix  afteroidcs  l:'pp!niicr  has  described  a  polymori)hous  fission 
fungus  or  hair  fimgus  found  in  the  pus  of  an  old  cerebral  ab.scess  causing  death  through 
meningitis.  Since  in  the  affected  individual  changes  similar  to  tuberculosis  were  found 
in  the  lungs  and  bronchial  glands  and  since  inoculation  of  guinea-jiigs  and  rabbits  gave 
rise  to  a  disease  resembhng  tuberculosis,  he  has  designated  the  di.sea.se  produced  by  the 
fungus  as  Pseudotuberculosis  cladnthrichica.  MacCallum  regards  Kpjiinger's  fungus 
which  he  obtained  from  a  jiurulent  peritoneal  exudate  as  belonging  to  the  Actinomyces 
group  and  calls  it  Actinomyces  asteroides.  Schahad  regards  a  fungus  characterized  by 
branching  threads  which  he' found  in  a  subpectoral  abscess,  and  according  to  its  behavior 
in  cultures  apparently  identical  with  the  Kjipinger  fmigus,  as  belonging  to  the  actino- 
myces group,  and  designates  it  an  atyjjical  actinomyces  which  dilTers  from  the  tyi)ical 
form  in  that  it  produces  no  clubs  and  is  acid-fast.  "Jn  animals  it  cau.sesap.seiidotuber- 
culosis. 

Buchholtz  found  a  variety  of  streptothrix  in  a  pneimionic  hmg  containing  large 
cavities  of  disintegration,  with  ragged  walls.  Lunger  found  a  streptothrix  patiiogenic 
for  guinea-pigs  in  the  sputum  of  a  thirteen-year-old  boy,  which  probably  arose  from  an 
oesophageal  diverticulum. 

According  to  investigations  by  Kanthack.  Boycc.  and  Vinnul  it  is  very  jjrobable 
that  the  di.sease  occurring  in  India  known  as  Madura-foot  or  Mycetoma,  characleriz.-d 
by  gradual  swellings  in  the  extremity,  with  nodular  tleposits  becoming  changed  into 
abscesses  and  fistulous  tracts  through  suppuration,  and  on  pressure  discharging  purulent 
gray,  or  brown  to  black,  fish-roe  or  trufflelike  granules  i.s  caused  l)y  a  ])olymorphous 
jungus  related  to  Actinnmycrs  and  designated  by  Vincent  as  Streptothrix  madunr.  Kan- 
thack regards  the  fuimus  \\  hich  is  enclosed  in  the  granules  as  identical  with  the  Actino- 
myces, but  the  investigations  of  Vincent  and  Boyce  do  not  agree  with  this  a.ssumplion. 
According  to  Boyce,  the  Streptothrix  madurw  occurs  in  two  varieties,  one  white  or  yellow, 
with  fine' dichotomous  branching  liireads  and  one  black,  with  branched  pigmented 
threads.  Vnna  and  Delbanco  also  distinguish  dilTerent  fungi  which  they  cla.ss  with  the 
Actinomvces.  According  to  Oitpcnlnimer  mycetoma  is  a  gramiloma  with  abs<-ess  for- 
mation caused  bv  two  kinds  of  fungi;  the  yellow  form  is  an  actinomyces,  while  (lie 
fungus  of  the  black  form  cannot  at  the  present  time  be  exactly  classified,  i)ut  probably 
belongs  to  the  oidia  or  moulds.  The  para.site  of  the  madura  di.sea.se  has  l)een  known 
since  the  ye.tr  1874  {Carter,  Lewis,  and  Cunningham),  and  was  fonnerly  called  Chmnyphc 
Cortcri. 


666  THE    PATHOGENIC    FISSIOX-FUXGI. 

Literature. 

(Actinomycosis.) 

Abee:  Drei  Falle  von  Aktinomykose.     Beitr.  v.  Ziegler,  xxii.,  1897. 
Behla:  Systemat.  Stellung  d.  Aktinomyces.     Cbl.  f.  Bakt.,  xxiii.,  1898. 
Berestnew:  Ueber  Pseudoaktinomykose.     Zeitschr.  f.  Hyg.,  xxix.,  1899. 
Bollinger:  Eine  neue  Pilzkrankheit  beim  Rinde.     Cbl.  f.  d.   med.  Wiss.,  1877;  Deut 

Z.  itschr.  f.  Thiermed.,  iii.,  1877;    Miinch.  med.  Woch.,  1887. 
Bostrom:  Unters.  uber  die  Aktinomykose  des  ^Menschen.     Beitr.  v.  Ziegler,  ix.,  1890o 
Chiari:  Darmaktinomykose.     Prag.  med.  Woch.,  1884. 

Gilbert:  Aktinomycesthermophilus  u.  Aktinomyceten.     Z.  f.  Hyg.,  47  Bd.,  1904. 
Grill:  Aktinomykose  d.  Magens  u.  d.  Darms.     Beitr.  v.  Bruns,  xiii.,  1895. 
Hesse:  Ueber  Aktinomykose.     Deut.  Zeitschr.  f.  Chir.,  34  Bd.,  1892. 
Hoche:  Histogenese  du  nodule  actinomycosique.     Arch,  de  med.  exp..  1899. 
Howard:  Actinomycosis  of  Central  Nervous  System  (Lit.).     Jour,  of  Med.  Res.,  1903. 
Hummel:  Entstehung  d.  Aktinomy  kosedurch  Fremdkorper.     Beitr.  v.  Bruns,  xiii., 

189.3. 
Illich:  Beitr.  z.  Khnik  d.  Aktinomykose,  Wien,  1892. 

Joline:  Deut.  Zeitschr.  f.  Tliiermed.,  vii.,  1881;    Cbl.  f.  d.  med.  Wiss.,  1882;  Aktino- 
mykose im  Samenstrang  kastrirter  Pferde.     Fortschr.  d.  Med.,  iii.,  1885. 
Israel",  J.:  Mykose  des  Menschen.     Virch.  Arch.,  74,  78  Bd.,  and  Cbl.  f.  d.  med.  Wiss., 

I'JS.a:    Klin.  Beitr.  z.  Kenntniss  d.  Aktinomykose  des  Menschen,  Berlin,  1885. 
Israel,  O,:  Kultivirbarkeit  d.  Aktinomyces.     Virch.  .\rch.,  95  Bd.;    Cbl.  f.   d.  med. 

\\  iss.,  1886. 
Krause:  Zur  Kenntn.  d.  Aktinomyces.     Cbl.  f.  Bakt.,  xxvi.,  1899. 
Kruse:  Systematik  d.  Streptotricheen  in  Fliigge.     Die  Mikroorganismen,  ii.,  1896. 
Lebert:  Anat.  path.  I  c.  Atlas  t.  I.,  pi.  II.,  Fig.  16. 

Levy:  Ueber  die  Aktinomycesgruppen.     Cbl.  f.  Bakt.,  xxvi.,  1899  (Lit.). 
Lieblein:  Aktinomykose  d.  Haut.     Beitr.  v.  Bruns,  27  Bd.,  1900. 
Liebmann:  L'Attinomyce  deU'  uomo.     Arch,  per  le  Sc.  Med.,  xiv.,  1890. 
Martin:  Actinomvcosis  of  the  Brain.     Journ.  of  Path.,  iii.,  1894. 

Mertens:  Aktinomycesforschung.     Cbl.  f.  Bakt.,  xxix.,  1901,  u.  Z.  f.  Hyg.,  42  Bd.,  1903. 
Moosbrugger:  Ueb.  die  Aktinomykose  des  Menschen.     Beitr.  v.  Brmis,  ii.,  Tubingen, 

18b6. 
vanNiessen:  Aktinorayces-Reinkultur.     Virch.  Arch.,  150  Bd.,  1897. 
Partsch:  Die  Aktinomykose  des  Menschen.     Samml.  klin.  Vortr.,  No.  306-7,  1888, 
Perroncito:  Inoculation  d'actinomyees.     Arch.  ital.  de  Biol.,  vii.,  1886. 
Ponfick:  Bresl.  Jirztl.  Zeitschr.,  1879,  9  Mai;   Berl.  klin.  Woch.,  1879,  p.  347;   Die  Akti- 

nomvkose  des  Menschen,  Berlin,  1882. 
ScMegel:  Aktinomykose.     Ergebn.  d.  allg.  Path.,  v.,  Wiesbaden,  1900,  u.  Handb.  d. 

].ath.  Mikroorg.'  ii.,  1903. 
Schiirniayer:  L'eber  Aktinomyces.     Cbl.  f.  Bakt.,  xxvii.,  1900. 
Tusini:  Aktinomykose  des  Fusses.     A.  f.  klin.  Cliir.,  62  Bd.,  1900. 
Virchow:  Trichinosis  u.  Aktinomykosis  bei  Schweinen.     Virch.  Arch.,  95  Bd.,  1884. 
WoljBfu.  Israel,  J.:  Reinkultur  des  A.  u.  Uebertrag.   auf  Thiere.     Virch.  Arch.,  126 

Bd.,  1S91. 
Wright:  Madura  Foot.     Jour,  of  Exp.  Med.,  1898;    Actinomycosis.     Ref.  Handb.  of 

Med.  Sc,  2d  ed.,  1900.    Biology  of  the  Microorganism  of  Actinomycosis.    Jour,  of 

Med.  Res.,  1905. 

For  literature  on  Streptothrix,  Cladothrix,  and  Leptothrix  see  facing  page. 

§  177.  In  addition  to  those  already  described  there  is  a  'iav^e  number 
of  bacilli  pathogenic  for  animals  which  may  also  cause  infection  in 
man.  The  most  important  animal  diseases  caused  by  bacilli  are  sympto- 
matic anthrax,  swine-erysipelas,  swine-plague,  swine-pest,  cattle-plague, 
and  chicken-cholera. 

Ihe  bacillus  of  blackleg  or  symptomatic  anthrax  (Bacterie  du  charbon  symjito 
mntiqrtfi,  ClostridiHm  xu rrapli fisematos  bovis)  is  a  rod  with  rounded  ends  about  3-5  /i  long 
and  0.5-0.6  ji  broad,  and  .sometimes  possessing  independent  motion.  According  to  the 
investigations  of  Bollinger,  Feser,  Arloing,  Comevin,  Thomas,  and  others,  it  is  constantly 
found  in  blackleg. 

Blackleg  occurs  particularly  in  young  cattle  and  in  lambs,  and  is  usually  fatal 
within  two  days.     It  is  characterized  anatomically  by  a  tiunor-like  swelling  of  the  skin 


I 


Literature. 

(Strepfothrix,    Vhidotlui.r,   oiul  l^rploihrl.r.) 

Axenfeld:  Pilzkonkiemente    in    Traneniolnchen.     JIaiulb.   d.  patli.    Miki-uore.    iii  , 

Jena.  I90;i 
Babes:  .Madurafuss.     Handh.  d.  path.  Mikroorg.,  iii.,  Jena,  1908. 
Boyce:  Plurality  of  FmiKi  in  Madura  I)isea.se.     Hyg.  Runds.,  1894. 
Buchholz:  MenWheni)atliogene  StreptDthrix.     Z.*f.  Hyg..  24  Bd.,  1S97, 
Carter:  .Mycetoma  or  the  Fungus  Disease  of  India,  London.  1S74. 
Eppinger:  Pathogene  Cladothrix.     Beitr.  v.  Ziegler,  ix.,  1891. 
Foulerton  and  Jones:  Pathogen.  Act.  of  the  Genus  .Strc[)tothrix.     I'lans.  of   the 

Path.  Soc.  of  London,  Uii.,"^1901. 
Gozzolino:  Ein  neues  Fadenbakteriuni.     Z.  f.  liyg.,  ;W  Bd.,   1900. 
Kanthack:  Madura  Disease  and  Actinomyces.     J.  of  Path.,  1892. 
Langer:  iStreptotrichosis  oesophagi.      Z.  f.  Hyg.,  47  Bd.,  1904. 
Lewis  and  Cunning-ham:  The  Fungus  Disease  of  India,  Calcutta,  187o. 
MacCallum:  On   the  Life-hi.story  of  Actinomyces  A.steroi(Ies.     ('.    f.   B.ikt.,    Prig., 

xxxi..  1902. 
Oppenheim:   Madurafuss.     A.  f.  Derm.,  71  Bd.,  1904  (Lit.). 
Petruschky:  Die  pathogenen  Trichomyceten.     Handb.  d.  palli.,  .Mikroorg.,  iii.,  .kiui, 

19(W  (Lit.). 
Sabrazes  et  Riviere:  Les  parasites  du  genus  streptothrix.     .Sem.  Med.,  1895. 
Schabad:  .Vctinomyces  atypica  p.seudotuberculoza.     Z.  f.  Hyg.,  47  Bd..  1904. 
Trolldenier:  Beim'llunde  gefund.   pathogene  Streptothrix.     Z,  d.  Tienned.,    vii., 

190:^. 
Unna  u.  Delbanco:  .Vnatomie  des    indischen    .Madunifusses.     M.    f.    praki.    Denn., 

1901.    , 
Vincent:  Ft.  sur  le  para.site  du  pied  de  .Madina.     .\nn.  de  I'liist.  i'asteur,  1S94. 


I 


INFECTIOI'.S    DISEASKS    OF    A.MIMALS.  HO? 

due  to  tho  exudation  of  a  bloody  serous  fluid  attended  1)V  tlic  format iuii  of  gas  in  ilu- 
subcutaneous,  intermuscular,  and  muscular  connective  tissue.  The  bacilli  are  found  in 
the  region  of  the  exudation  and  gas-formation,  as  well  a.s  in  tlie  spleen  and  liver,  'i'liey 
do  not  stain  with  Cram's  method. 

According  to  Arloing,  Cornevin,  and  Thomas,  the  bacilli  may  be  cultivated,  in  the 
absence  of  oxygen,  in  chicken-bouillon,  to  which  a  small  amount  of  glycerin  and  sul- 
phate of  iron  is  added.  Kitasato  and  Kitt  cultivated  then\  in  guinea-pig  bouillon,  agar, 
and  gelatin  in  the  absence  of  oxygen.  They  grow  best  at  from  .'{(l  -;5.s"  C'.,  and  form 
spores  in  the  midtUe  or  at  the  ends  of  the  rods,  wliereliy  the  latter  become  .somewhat 
swollen.  Tlic  addition  of  sugar  and  glycerin  to  tiie  nutrient  medium  aid.s  the  growth. 
The  inoculation  of  cattle  and  sheep  with  l)acilli  which  are  attemiated  by  beating  i)ro- 
duces  an  immunity  against  virulent  bacilli.  Cattle,  sheep,  goats,  rabbits,  guinea-pigs, 
swine,  dogs,  cats,  and  chickens  are  susceptible  to  the  bacilli  of  .sjTnptomatic  anthrax; 
black  rats  are  immime;    horses  and  donkeys  occupy  an  intermetliate  jiosition. 

The  inoculation  of  guinea-pigs  with  virulent  material— for  example,  with  the  dried 
juice  of  the  muscle  of  cattle  dying  of  blackleg— leads  very  tjuickly  to  :i  rapidly  spread- 
ing swelling  at  the  point  o  inoculation,  due  to  the  infi'ltration  of  tiie  tissues  with  a 
bloody  oedema.  The  bacilli  spread  with  remarkable  rapidity  in  the  tissues,  particularly 
in  the  subcutaneous  and  intermuscular  tissue,  and  penetrate  also  into  the  muscles.  They 
cause  severe  lesions  of  the  v  jssels,  leaHing  to  haemorrhages  and  serous  exudations,  and 
after  a  time  to  an  abundant  emigration  of  leucocytes.  The  animals  usually  ilie  on  the 
second  or  third  day  after  tue  swelUng  has  spread  over  a  portion  of  tlie  body.  The  blood 
usually  remains  free  from  bacilli.     Spores  are  not  formed  in  the  living  body. 

Literature. 

Arloing,  Cornevin  et  Thomas:  Lc  Charbon  symptomatiipie   ile  Ixruf,    Paris,    ],S.s7. 

Hess:   iJer  Rausclibrand.     Tliiermed.  Vortr.,  1888,  No.  4. 

Kitasato:  Der  RauschbrandbaciUus.     Zeitschr.  f.  Hyg.,  vi.,  1SS9,  viii.,  1890. 

Kitt:  Der  Rauschbrand.     Cbl.  f.  Bakt.,  i.,  1887;    Deut.  Zeitschr.  f.  Thiermed.,  xiii., 

1887;    Rauschbrand.     Handb.  d.  path.  Mikroorg.,  ii.,  190:5. 
Roger:  Charbon  sjonptomatique.     Rev.  de  med.,  1S91. 
Rogowitscli:  Wirkung  der  Rauschbrandlxvcillcn.     Beitr.  v.  Zicglcr,  iv.,  1889. 

The  Bradsot  Bacillus  is  an  anaerobic  bacillus  closely  related  to  that  of  sjiTipto- 
matic  anthrax.  It  forms  spores  and  at  times  possesses  numerous  flagella,  and  causes 
the  disease  of  sheep  known  as  Bradsot  or  Brausot,  which  is  found  particularly  in  the 
northern  portions  of  Europe.  The  sheep  dying  from  the  disease  show  a  liirmorriiagic 
serous  inflammation  of  the  stomach,  haemolysis,  and  serous  inflammation  of  the  coTi- 
nective  tissue,  at  times  with  gas  formation  {Jensen,  "  Bradsot."  "  ll.ind.  d.  path. 
Mikroorg.,"  ii.,  Jena,  1903). 

The  bacillus  of  swine-erysipelas  (Loffler,  Lnjdtin,  Schottellu.s,  and  Schiilz)  is  a 
bacillus  from  O.G-1.8  jx  long.  It  may  be  cultivated  in  bouillon,  meat-infusion-pei)tone- 
gelatm,  blood-serum,  and  sour  milk  at  18  -40"  C. 

In  gelatin-plates  it  forms  pecuhar  radiating  nntl  branched  figures.  Jn  stab-cult ure.s 
it  grows  out  in  white  streaks  from  the  stab-canal  like  the  bristles  of  a  test-tul)e  i)rush. 
In  cultures  the  bacilli  may  form  pseudothreads.  By  means  of  j-.ure  cultures  the  disea.se 
may  be  reproduced  in  susceptible  swine.  House-mice  and  i)igeons  die  within  two  to 
four  days  after  inoculation,  and  their  blood  contains  numerous  l)acilli. 

In  rabbits,  inoculation  is  followed  by  an  erysipelas-like  inflammation  which  tenni- 
nates  either  in  a  fatal  general  infection  or  in  healing.  Guinea-pigs  and  chickens  aro 
immime. 

According  to  investigations  by  PasL"W  and  Thuillkr,  and  confimicJ  by  Scliollch'us 
and  Schiitz,  the  virulence  of  the  bacilli  for  swine  may  be  attemiated  by  progressive  in- 
oculations in  rabbits.  Susceptible  swine  inoculated  with  this  vaccine  do  not  die  after 
inoculation  and  become  immune  to  fully  virulent  bacilli. 

Swine-erysipelas  occurs  particularly  in  youi»g  herds  of  liighly-bnMl  (luigli.sli)  hogs, 
while  the  common  breeds  are  nearly  or  wli'olly  immune.  The  disease!  is  characterized 
by  fever  and  the  appearance  of  red  spots,  later  becoming  brown,  upon  the  neck,  chest, 
and  belly.  Intestinal  haemorrhages  occasionally  occur.  -More  tiian  iialf  of  the  infected 
animals  die,  usually  within  a  few  hours  or  within  four  days.  The  autopsy  .shows} 
swelling  and  localized  haemorrhages  in  the  mucosa  of  the  int"stine,  swelling  and  ulcer- 
ation of  the  follicles,  particularly  in  the  ileoca-cal  region,  .swelling  of  the  me.sentcric 
lymph-glands,  and  petechia'  of  the  serous  membranes. 

The  bacilli  are  found  in  the  blood  as  well  as  in  tiie  lympli-giands,  muscles,  spleen, 


668  THE    PATHOGENIC    FISSION-FUNGI. 

and  kidneys,  where  they  also  He  in  the  blood-vessels.     The  majority  are  free;    some  are 
enclosed  in  leucocytes.'    Tliey  are  stained  by  Gram's  method. 

Literature. 

Hess-  l)er  St-ibchcnrothlauf  u.  die  Schweineseuche.     Thiermed.  Vortr.,  i.,  1888. 
Kitt:   Der  Stal)chenrothlauf  der  Schweine  imd  dessen  Schutzimpfung.     Jahresb.    d. 

Thierarzneisch.,  Miinchen,  1885-86,  Leipzig,  1887;    Streptothrixform  d.  Bacillus. 

Cbl.  f.  Hakt..  xxii..  1897. 
Loffler:  Schwoinerothlauf.     Arb.  a.  d.  K.  Ges.-Amte,  i.,  188.5. 
Lorenz:  Schutzimitfung  gegen  Schweiiierothlauf.     Cbl.  f.  Bakt.,  xv.,  1894. 
Lydtin  untl  Schottelius:  Der  Rotlilauf  der  Schweine,  Wiesbaden,  1885. 
Preisz:  Rotlilauf  d.  Schweine.     Handb.  d.  path.  Mikroorg.,  iii.,  1903. 
Schiitz:  Rotlilauf  d.  Schweine.     Arb.  a.  d.  K.  Ges.-Amte,  i.,  1885. 

The  Bacillus  suisepticus,  the  cause  of  German  swine  plague  or  swine  septicoemia 
{switie  plague  [Salmon])  is  a  bacillus  discovered  by  Loffler  in  1886.  It  is  about  1.2-1.4  /t 
long  and  0.4-0.6  /i  broad.  It  is  a  facultative  aerobe,  grows  easily  upon  the  ordinary 
culture  media,  and  when  stained  usually  shows  a  polar  staining  while  the  middle  portion 
remains  clear.  In  natural  infection  the  hogs  may  die  within  twenty-four  hours  froni 
septicaemia  and  bacteria?mia.  The  bacilli  may  be  found  in  all  the  organs.  If  the  skin 
is  the  avenue  of  entrance  there  occurs  at  tliis  point  a  eubcutaneous  inflammatory  oedema. 
More  frequent  is  tlie  form  known  as  pectoral  sivine  plague,  which  occurs  both  in  an  acute 
and  a  chronic  form.  In  the  former  there  occur  multiple  croupous-hsemorrhagic  broncho- 
pneumonias that  become  gangrenous,  and  may  be  associated  with  a  pleuritis,  pericar- 
ditis, and  peritonitis.  In  the  chronic  form,  which  is  the  most  common  in  Germany, 
pulmonary  hepatizations,  with  or  without  necrosis,  are  formed.  In  the  majority  of 
cases  it  is  a  bronchogenic  pulmonary  disease,  but  the  infection  may  take  place  through 
wounds  or  the  intestine  and  secondarily  reach  the  lung.  Hogs,  mice,  rabbits,  and 
guinea-pigs  are  susceptible  to  inoculations;  pigeons,  chickens,  and  calves  less  so,  and 
dogs  and  horses  still  less.  The  bacillus  produces  a  local  inflammation.  If  it  passes 
from  the  lymphatics  into  the  blood  there  occurs  a  marked  increase  of  the  bacilli,  par- 
ticularly in  the  lung  and  liver  (Joest:  "  Schweineseuche  und  Schweinepest."  "Handb. 
d.  path.  Mikroorg.,"  iii.,  190.3). 

Tlie  Bacillus  of  Swine  Pest  or  the  American  Sivine  Plague  (hog  cholera  [Salmo7i], 
swine  j)l<i</i/c  [Hillinysl  swine  fever  [Brown]),  the  Bacillus  suipestifer  {Bacillus  cholera; 
suis  [Smith]),  forms  rods  with  rounded  ends  about  1.2-1.8  /z  long  and  0.6  /i  broad. 
It  does  not  stain  by  Gram's  method.  When  stained  with  basic  aniUne  dyes  it  shows 
in  part  a  polar  or  peripheral  stain.  It  may  easily  be  cultivated  on  the  ordinary  media, 
is  a  facultative  aerobe,  moves  by  means  of  numerous  flagella,  and  produces  no  spores. 
The  plague  is  endemic  in  North  America,  and  has  been  introduced  thence  into  Europe. 
It  occurs  in  two  chief  forms.  The  septiccemic-hceynorrhagic  form  is  characterized  by 
heemorrhages  in  various  organs,  particularly  the  lymph-glands,  serous  membranes, 
intestine,  and  kidneys.  In  the  intestinal  form,  which  is  more  frequent,  inflammatory 
changes  are  found  in  the  intestinal  tract,  particularly  in  the  colon,  bearing  in  part  the 
character  of  catarrhal  or  in  part  croupous,  hajmorrhagic,  and  diphtheritic  inflammations. 

The  infection  takes  place  chiefly  through  the  intestinal  tract,  where  the  most 
severe  changes  are  found.  Through  the  transportation  of  the  bacilli  through  the  lymph 
and  blood  changes  in  other  organs  are  produced  and  a  septicaemia  or  bacterisemia. 
Mice,  rabbits,  guinea-pigs,  and  white  doves  are  suscejitible  to  inoculation;  horses,  sheep, 
and  cattle  are  not  killed  by  inoculation;    local  inflammations  alone  are  produced. 

Swine  pest  and  swine  plague  may  occur  in  the  same  individual  as  a  mixed  infection, 
and  may  infect  wliole  herds.     Such  epidemics  are  characterized  by  great  virulence. 

Literature. 

Salmon  and  Smith:  Investigations  of  Infectious  Animal  Diseases.  Ann.  Rep.  of  the 
Bureau  of  Aniin.  Industry,  vi,  and  vii.,  Washington,  1889  and  1890;  and  Hog 
Cholera,  Wasliiiigton,  1889. 

Joest:   Schwcinescuclie  und  Schweinepest.     Handb.  d.  path.  Mikroorg.,  iii.,  Jena,  1903. 

Preisz:  SchwcinciK'st  und  Schweineseptikamie.     Z.  f.  Tiermed.,  ii.,  Jena,  1898. 

Karlinski:  Scliweineiiest  imd  Schweineseuche.     Z.  f.  Hyg.,  28  Bd.,  1898. 

The  Bacillus  of  House  Typhoid  is  a  bacillus  observed  by  Loffler  in  an  epidemic 
of  mice  kept  in  the  la))oratory.     House  niic'(>  and  field  mice  are  very  susceptible  to  it. 


IXFECTIOrs    DISKASKS    OF    WINfAI.S.  CCO 

It  may  be  used  as  a  means  of  extermination  of  field  mire.  (Loflk-r:  "  Ki>iileitiic(ii 
unter  den  im  hyg.  Institut.  zu  Greifswahi  gehaltenen  Mausen  und  idx-i-  ilic  lickamp- 
fungder  Feldma'useplage,"  Cbl.  f.  Bakt.,  xi.  u.  xii.,  lS<)-_'. ) 

The  bacillus  Of  chicken-cholera,  or  «(■/(//(  typhoid,  or  bin!  septicwmla,  a  disease 
occurring  eiiideniically  among  cliiokcns.  is  a  small  bacillus  from  11. "J  /(  long,  often 
somewhat  constricted  in  its  middle.  Jt  was  first  studied  by  Ptrnmciln.  then  by  Tous- 
saint,  Pasteur.  RIvolta,  Marchidfava,  Cdli,  and  Kilt.  It  (kK\s  not  stain  by  (iram's 
method.  The  ilisease  is  characterized  clinically  by  gn>at  exhaustion  and  stui)or. 
occasionally  also  by  iliarrluieal  intestinal  discharges;  anatomically  by  swellings  of  the 
liver  and  spleen,  lurmorrhages  and  inflammations  of  the  intestine,  and  also  fn-cjuently 
by  pleuritis  and  i)ericartlitis. 

The  bacilli  are  found  ir.  the  blood  ami  therefore  also  in  the  capillaries  of  the  differ- 
ent tissues.  They  may  be  cultivated  upon  nutrient  gelatin,  l)lood-seruin,  and  neiilral- 
ized  bouillon,  as  well  as  upon  potatoes.  They  form  white  colonies.  I-Yvding  or  inocu- 
lation of  the  bacilli  causes  in  chickens  a  tj^jical  chicken-cholera;  pigeons.  si>arrows, 
pheasants,  rabbits,  and  mice  are  also  susceptible  to  the  bacilli.  In  sheep,  horses,  and 
guinea-pigs  they  produce  abscesses  at  the  point  of  inoculation. 

Literature. 

Gamaleia:   Aetiologie  der  Huhnercholera.     (1)1.  f.  Hakt..  iv..  ISSS. 

Kitt:  (H'tiiigelcholera.     Cbl.  f.  Bakt..  i.,  1887;    Deut.  Zcitsehr.  f.  Thiernied.,  xiii.,  ISHS. 

Pasteur:  Compt.  rend.,  xc,  1880. 

Wertheim:  Cholera  gallinarum.     A.  f.  exp.  Path.,  26  Bd..  isso. 

Ziirn:   Die  Krankheiten  des  Hausgefliigels,  Weimar,  1882. 

The  Bacillus  diphtheriae  columbarum  is  a  small,  .slender  bacillus,  which  was 
i-olated  by  Loftier  ("  Mittheil.  a.  d.  k.  Gcs.-Amtc,"  ii.)  from  the  exudate  of  a  pitreon 
lying  of  diphtheria,  and  is  regarded  (Babes  and  Pu.^carin.  "  I'nters.  liber  die  Diphtheric 
''T  Tauben,"  Zeitschr.  f.  Hyg.,  viii.,  1890)  as  the  probable  cause  of  pigeon-diphtheria, 
disease  resembling  human  diphtheria.  Loffler  was  able  to  reproduce  the  disease  in 
u:eons,  but  not  in  chickens,  by  means  of  inoculation  of  pure  cultures  of  the  bacilli. 
>lice  died  in  about  five  days  after  inoculation,  and  the  bacilli  were  found  in  the  blnod- 
\  cssels  of  all  the  organs.  Streit  ("  Unters.  fiber  Gefliigel-Diphtherie,"  Z.  /.  Hyg..  4()  Bd.. 
l'M)4)  found  a  bacillus  in  chicken  diphtheria  which  he  was  able  to  cultivate  and  inoculate 
-  iccessfuUy  in  pigeons. 

As  the  Necrosis  Bacillus  (Bacillus  necrophorits,  Flilgge;  Bacillus  necroseos, 
^"lomonsen:  Strcptothri.v  necrophora,  Kitt,  Streptothrix  canicula.  Schmorl)  there  has 
til  en  described  an  anaerobic  bacterium  (Jen.sen:  ''  Xekrose  Bacillus."  "  Handli.d.pathoi;. 
Mikroorg.,"  ii.,  Jena,  1903)  which  forms  rods  and  unbranched  threads,  does  not  stain 
iKcording  to  Gram's  method,  and  produces  gas  in  cultures.  It  has  Ijeen  ol,.u'rved  in  all 
the  domestic  animals,  including  the  chicken.  It  cau.ses  inflammations  m  the  hoof  of 
tlie  horse,  cattle,  and  reindeer,  and  on  the  tail,  foot,  and  udder  of  swine  and  cows,  and 
i<  the  cause  of  the  so-called  calves'  diphtheria  (Loffler).  ral>bit  diphtheria,  and,  perhai)s, 
;il-o  in  part  of  avian  diphtheria.  In  hogs  also  it  causes  necrotic  inflamniation  of  the 
mouth  and  nose.  It  has  been  found  also  in  inflanmiations  of  the  colon  in  hoi-ses.  and 
in  the  vagina  and  in  the  uterus  of  cows,  and  in  the  inflamed  umbilical  cord  of  calves. 
It  can  also  produce  metastases  in  the  internal  organs.  It  occurs  in  the  regions  named 
aliove.  and  aLso  in  other  parts  of  the  body,  partly  as  a  primary  infection,  and  partly 
-'■condary  to  some  other  infection. 

Besides  the  above,  there  are  many  other  bacilli  which  have  been  described  as  the 
rinse  of  disease  in  animals.  Thus,  for  example,  according  to  Hoflich  ("  Die  Pye- 
liitiephritis  bacillosa  des  Rindes."  Monatsh.f.  prakt.  Thierheilk.,  ref.  C<ntralb.j'.  Bakt.,  \.) 
:iiiil  Enderlen  ("  Primare  infectiose  Pyelonephritis  beim  Kinde."  Deutsch.  Zeitschr.  f. 
Thiernied.,  xvii.,  1891,  ref.  Cent.  f.  Bakt.,  x.),  the  frefjuently  occurring  pyelonephritis 
lit"  cattle  is  caused  by  a  bacillus.  Likewise,  according  to  Xocard  ("  Not*-  sur  la  inaladie 
lies  bceufs  de  la  Guadeloupe  connue  sous  le  nom  de  Farcin."  Ann.  de  I'ln.  Past.,  ii..  18KS) 
the  irorm  /tisease  of  the  o.x,  which  was  formerly  of  fre(pient  occurrence  in  France;  and 
according  to  Oresie  and  Armanni  {"  Studii  e'ricerche  intorno  al  barbone  dei  hnfali," 
ref.  Cent.  f.  Bakt.,  ii.,  1887)  and  von  Ratz  {"  Die  Barbonekrankheit."  Deutsrh.  Zeit.'ichr. 
f.  Thiermed.,  xxii.,  1896),  the  plague  occurring  among  the  Italian  buffalo  known  a.s 
hnrhone  dei  bufali  is  due  to  a  bacillus  (by  Voges  regarded  as  the  bacillus  of  huMnorrhagic 
-iptica?mia). 

In  t\\Q  dysentery  of  calves  different  bacilli,  including  the  bacterium  coli.  have  been 
described  as  the  cause  (Joest-  "  Untersuchungen  uber  Kiilbemihr,"  Z.  f.  Tiermcd.,\\\., 
Ji  na,   190;^;   Jensen:    "Handb.  d.  path.    :Mikroorg.,"  iii.,  Jena,  1S)(»3).     According  to 


670  THE    PATHOGENIC    FISSION-FUNGI. 

yocard  and  Jioiix  ("Le  microbe dc  In  peripneumonie,"  A/ni.  del' Inst.  Pastenr,  1898),  the 
lung  plague  of  cattle  is  cliaracterized  by  a  very  small,  lively  motile  bacillus  whose  form  is 
determined  with  difficulty.  According  to  Ba7ig  ("  Aetiologie  des  seuchenhaften  Ver- 
werfens,"  Ze/^sc/ir.  /.  Tiermed.,  i.,  1887)"  and  Preisz  ("Bacillus  des  seuchenhaften 
Verwcrfens,"  C.  f.  B.,  Orig.,  xxxiii.,  1903)  bacilli  cause  the  epidemic  abortion  of  cattle, 
Lundgren  ("  Die  Renntierpest,"  Zeitschr.  f.  Tiermed.,  ii.,  1898)  and  Bergman  {''  Renn- 
tierpest  und  Renntierpestbacillen,"  ib.,Y.,  1901)  on  the  ground  of  their  investigations 
regard  certain  bacilli  as  causing  reindeer  plague.  The  contagium  of  reindeer  pest  is  yet 
unknown  {Kolle:  "  Hinderpest, " Ergehn.d.aUg.  Path.,  vi.,  Wiesbaden,  1901).  Likewise 
the  cause  of  the  hoof-and-mouth  disease  is  still  unknown  {Loffler:  "  Bericht  iiber  d.  Un- 
tersuch.  d.  ii.  preuss.  Kommission,"  D.  med.  Woch.,  1903).     It  passes  through  all  filters. 

3.  The  Spirilla  and  the  Diseases  Caused  by  Them. 
(a)  General  HemarJcs  vpon  the  SjnriUa. 

§  178.  The  Spirilla,  or  Spirillaceae,  or  Spirobacteria  are  divided  into 
two  geuera,  one  of  them  called  kSjuriUir.n..  the  other  Sjyirochcete.  Many 
writers  recognize  still  another  genus,   Vibrio. 

The  genus  Spirillum  is  characterized  by  the  formation  of  short,  stiff, 
shallow  spirals,  which  in  part  possess  ilagella  and  show  an  active  swarm- 
ing movement.     The  wavy  rods  are  also  cal  led  vibriones  by  many  writers. 

The  genus  Spirochaete  is  characterized  by  long,  llexible,  closely 
turned  spirals. 

The  Spirochwte  plicatiUs  fornxa  long,  very  fine,  closely  wound  threads, 
from  100-225  /j.  long;  it  is  of  frequent  occurrence  in  swamp-water  and  iu 
gutters,  and  makes  very  rapid  movements. 

Spirochaete  buccalis  sive  denticola  is  10-20  //  long,  pointed  at  both 
ends,  and  is  not  infrequently  observed  in  the  secretions  of  the  mouth  and 
nose  (cf.  Fig.  19G).     It  appears  to  possess  no  j^athogenic  significance. 

Spirillum  sive  Vibrio  rugula  (Fig.  512,  6)  forms  rods,  from  6-16  fi  long  and  0.5-2.5  /z 
,  broad,  simply  bent  or  having  a  shallow  turn,  and  moves  by  means  of  flagella.  It  occurs 
in  swamp-water,  faeces,  and  in  the  slime  from  the  teeth. 

Spirillum  sive  V^ibrio  serpens  forms  thin  threads  from 
11-28  n  long,  having  three  to  four  wavy  turns,  and  is 
found  in  stagnating  fluids. 

Spirillum  tenue  has  very  thin  threads  about  3-15  n 
long,  having  2-5  screw-like  turns. 

Spirillum  undvla  (fig.  512,  a)  consists  of  a  thread 
from  1-1.5  fi  broad  and  8-12  fi  long,  having  from  one  and 
a  half  to  three  turns,  and  furnished  with  a  flagellum  at  one 
end.  It  occurs  in  various  decomposing  fluids  and  executes 
rapid  twisting  and  darting  movements.  Fig.  SVZ.—SpiriUum  or  Vi- 

Svirillum  volutaiis  possesses  threads  1 .5-2  tJ.  thick  and  hrio  re gxil a  {b)  a.ud  Spiril- 
25-30 /.long,  with  two  and  a  half  to  three  and  a  half  ^^i'l^f^^'^S 
turns,  and  beanng  a  riagellum  at  each  end.  chopped  earth-worms.    Dried 

According    to    Prozmowski,    Spirillum,    rugula     causes      preparation  treated  with  gen- 
decomposition    of    cellulose,    and    forms    terminal   spores.      tian-violet.    x  tiOO. 
According  to  Wcibel,  a  vibrio  present  in  nasal  slime  presents 
many  forms  of  growth.     Esmarch  succeeded  in  cultivnting 

a  spirillum,  called  by  him  Spirillum  rubrum,  upon  the  various  ordinary  media.  In 
bouillon  it  forms  spirals  of  from  forty-three  to  fifty  turns.  Short  spirilla  execute 
lively  movements,  but  long  ones,  on  the  contrary,  slow  movements,  or  are  motion- 
less. The  colonies  in  firm  nutrient  media  are  at  the  beginning  pale,  but  in  time  the 
portions  not  exposed  to  the  air  take  on  a  wine-red  color.  In  the  spirilla  of  old  cult- 
ures there  appear  three  to  four  clear,  dull-glistening  spots  that  do  not  stain,  and  are 
probably  to  l)e  regarded  as  spores.  Cultures  which  contain  such  spirilla  are  more  re- 
sistant to  drying  than  others,  but  they  are  very  easily  killed  by  heat. 

The  long  sjMrals  may  break  up  into  short  segments  which  possess  only  about  three- 
quarters  of  a  turn,  but  these  may  again  grow  in  length,  and  undergo  division.  Branch- 
ing has  been  observed  many  times  {Kutscher,  Zcttnow,  Reichenback). 


spi  kit.lv,  671 

Literature. 

{Li fr -hist or  11  of  thv  Spiri/hi.) 

Esmarch:  Ueber  die  Reiiikultur  eiiies  Spirillum.     ("1)1.  f.  liakt.,  !..  ISST. 
Kitasato:  Reinkultur    eiiies    Spirilliiiu    au.s    faulciulcm    Hluto!'     ("hi     f     li:,kt      iii 

1S8S.  "       ■' 

Kutscher:    Vibrioncii  ii.  Spirillonfloru  d.  Diingerjauche.     Zoitsclir.  f.  Jiyi:.,  \x.,  1S9.5: 

Spirillum  I'ndula  minus  u.  ma.jtis.     ("1)1.  f.  Bakt..  xviii.,  189"). 
Prazmowsky:    riiters.   iib.   die  Kiitwit-ici'lungsgeschichtc  c'iniger  liaklcricu    Lcipzi" 

ISSS. 
Reichenbach:  I'cber  VerzweigungcMi  bci  Spirillon.     Cbl.  f.  Rakt.,  xxix..  I'.HIl. 
Salomon:  Spirillum  d.  Saugetliiermagt-us.     Cbl.  f.  liakt..  xix.,  ISiHi. 
Weibel:  Untersuchungen  iiber  Vibrioncn.     ("bl.  f.  Bakt.,  ii.,  1SS7,  iv.,  1888. 
Zettnow:  Bau  der  grossen  Spirillcu.     Z.  f.  Hyg.,  xxiv.,  1897. 

{h)   The  Pathogenic  SjtiriJIo. 

§  179.  The  Spirillum  cholerae  asiatics,  or  the  Vibrio  ehoJerce,  also 
called  comma-bacillus  (bacitle-cirf/ule  cholerif/ene),  was  discovered  by  R. 
Koch  in  1884,  and  is  regarded  as  the  cause  of  Asiatic  cholera.  The 
spirilla  (Fig.  513)  form  small  comma-like,  curved  rods,  fi-om  <).S-2  ,".  long. 

Cultures  of  cholera-spirilla  may  be  obtained  upon  a  great  variety  of 
culture-media  of  a  slightly  alkaline  reaction.     The  temperatures  most 
favorable  for  their  develoi)ment  lie  between  2.")°  mid 
30°  C.  ;  at  between  16°  and  8"  C.  they  are  still  capa-       ^_^  r        it 
ble  of  a  feeble  development.  -^  ^  f    ^  *"  j-^ 

In    fluid  media  in  the  presence   of  o.x:ygen   they  "^[l    ^     ~^^ 

show  lively  movements  that  may  be  easily  observed  in        ^   ^^^    ^^'^^ 
the  hanging  drop.     The  movements  are  produced  by  "^^    ^     "^^ 

means  of  a  terminal  fagellum.  Fir,..-,i3.-ciioiera- 

,^ri  -     •  '    J.  i       Ai         •    J     J-      7    J        J       *•     spirilla  from  a  piirt' ciil- 

W  hen  gaining  entrance  to  the  intestinal  tract  of  tlire.  ("..ver-piu.ss  prep- 
man  the  spirilla,  in  so  far  as  they  ai-e  not  destroNcd  "^^If^l^;  f"^;;';;'  ^^*-" 
by  the  action  of  the  gastric  juice  or  their  growth 
otherwise  prevented,  develop  both  in  the  small  and  large  intestines, 
and  their  multiijlicatioii  is  followed  by  a  maiked  ti-ansndation  from 
the  intestinal  mucosa,  so  that  the  intestines  becomes  filled  with  a  fluid  re- 
sembling meal-soup  or  rice-watei",  in  which  flakes  of  des(|uainat«'d  epi- 
thelium which  has  undergone  mucoid  degeneration  float  about. 

The  spirilla  are  always  ])resent  in  great  numbers  in  tlie  inle.siiii;il  ( - 

tents,  and  are  found  in  tlie  Inmina  of  tlie  inleslinal  glands,  whence  llu-y 
may  penetrate  lietween  and  beneath  the  ei)iliielial  cells. 

In  recent  cases  the  spirilla  may  usually  be  <lenioiisliate(l  in  co\er- 
glass  preparations  stained  with  meliiylene-blue  or  fnchsin.  Fresii  tlejecta, 
as  well  as  soiled  linen,  are  suitabU^  for  the  examination,  since,  according 
to  observations  made  by  Koch,  thespirillamay  multiply  actively  for  some 
time  upon  moist  linen'and  moist  earth.  In  old  cases  the  demonstration 
of  the  spirilla  is  more  ditlicult,  bnt  nevertheless  sncceeds  in  all  cases,  and 
is  attainable  most  surely  by  means  of  ]»late-cnltnres. 

Tho.  presence  of  cholera-spirilla  in  the  intesliue  e.rcitrs  an  injlamniation, 
which  in  the  beginning  finds  exjiression  in  i-edness,  swelling,  mark«-d 
transudation,  mucoid  degeneration  of  the  epithelium,  aiul  des(|iiamati<»n  ; 
later,  by  hfemorrhages,  formation  of  sloughs,  and  idceration.  It  is  char- 
acterized constantly  by  a  more  or  less  maiked  cellular  inliltration  of  the 


C72  THE    PARASITIC    FISSION-FUNGI. 

tissues.  The  solitary  follicles  and  Peyer's  patches  are  swollen  even  in 
fresh  cases.  Death  inay  take  place  after  a  few  hours  or  after  one  to 
three  days.  If  the  disease  lasts  a  longer  time,  the  intestinal  contents 
become  more  consistent  and  the  intestinal  mucosa  shows  ulcerative 
changes. 

According  to  our  j^resent  knowledge,  the  spirilla  produce  poisonous 
substances  w^hich  cause  local  damage  to  the  mucosa  of  the  intestinal 
canal,  and  when  absorbed  give  rise  to  symptoms  of  intoxication  and 
cause  paralysis  of  the  vessels.  Small  foci  of  degeneration  are  often  pres- 
ent in  the  liver  and  kidneys,  within  which  the  gland-cells  show"  cloudy, 
fatty,  or  hyaline  degeneration,  or  are  necrotic.  Moreover,  the  kidneys 
may  frequently  show  cloudiness  caused  by  a  toxic  degeneration  of  the 
epithelium ;  occasionally  also  a  swelling  of  the  cortex.  Ecchymoses  in 
the  epicardium  are  of  frequent  occurrence,  and  in  the  later  stages  patches 
of  necrosis  may  also  occur  in  the  mucous  membrane  of  the  vagina.  The 
long-continued  presence  of  spirilla  in  the  intestine  may  give  rise  to  ulcer- 
ation. Finally,  the  spirilla  may  be  crowded  out  by  the  putrefactive  bac- 
teria present  in  the  intestine,  and  ultimately  die  out.  Through  the 
absorption  of  the  products  of  decomposition  a  new  intoxication  may 
arise,  which  is  not  dependent  upon  the  original  gj)irilla. 

According  to  Koch,  Xicati,  and  Eietsch,  cholera-spirilla  may  also  be 
found  in  the  vomitus.  Nicati,  Eietsch,  Tizzoni,  andCattani  found  them  j 
also  in  the  ductus  choledochus  and  in  the  gall-bladder.  According  to 
the  statements  of  these  authors  the  spirilla  usually  do  not  enter  the 
blood,  but  in  cases  of  severe  infection  they  may  be  spread  throughout 
the  body. 

Koch  demonstrated  the  presence  of  spirilla  in  a  tank  in  India  which 
furnished  the  inhabitants  of  the  region  Avith  their  entire  sujjply  of  water 
for  drinking  and  other  purposes,  at  a  time  when  a  part  of  the  inhabi- 
tants were  sick  and  dying  of  cholera.  Since  then,  they  have  often  been 
demonstrated  in  water-supplies  during  cholera  epidemics. 

Asiatic  cholera  is  endemic  in  Lower  Bengal  and  never  entirely  disap- 
pears there.  Thence  it  spreads  at  times  throughout  India,  and  is  carried 
by  transportation  over  a  larger  or  smaller  pai't  of  the  world.  Since  the 
spirilla  are  easily  killed  outside  of  the  body  the  transportation  must  be 
effected  mainly  by  individuals  suffering  from  the  disease.  The  infection 
probably  occurs  exclusively  through  the  alimentary  tract,  as  the  re- 
sult of  the  introduction  of  infected  beverages,  food,  or  some  other  sub- 
stance into  the  mouth ;  but  without  doubt  not  every  introduction  of 
cliolera-sj)irilla  into  the  intestinal  canal  is  followed  by  infection. 

Moreover,  it  not  infrequently  happens  that  the  spirilla  increase  in  the 
intestine,  but  excite  only  slight  changes,  so  that  the  infected  individual 
suffers  no  marked  symptoms,  and  the  diagnosis  can  only  be  made  through 
the  demonstration  of  spirilla  in  the  stools. 

If  the  cholera-spirilla  get  into  the  water-supply  and  there  increase, 
cholera  may  develop  in  the  given  region  with  very  great  rapidity.  If, 
on  the  contrary,  the  infection  takes  place  by  direct  or  indirect  contagion 
from  man  to  man,  the  spread  is  slow,  in  tliat  the  disease  is  confined  to 
those  who  come  into  contact  with  the  sick,  or  with  articles  contaminated 
l)y  the  latter.     The  incubation  period  is  from  one  to  tMO  days. 

In  the  intestines  of  convalescents  the  spirilla,  according  to  investiga- 
tions of  Kolle,  may  live  for  a  long  time  and  multiply  without  giving  rise 
to  any  symptoms  betraying  their  presence.     Kolle  was  able  to  demon-  ! 


CIlOLi'.IJA, 


C7:i 


Strate  tlioni  in  a  nuiuber  of  cases  aflcr  lixc  to  riulih-rn  .l;iys.  and  in  indi 
vidual  cases  as  \ouis:  J»s  hveiity  to  Inrty-cijilil  (la.\s. 

One  attack  of  cholcia  makes  tlie  indix  idnal  ininiuiie  \\>\-  a  certaii 
time.  The  immunity  depends  upon  tlie  presence  of  hach-ricidal  anti 
bodies.  Tlii()n<ili  these  bodies  tlie  orjianism  may  l)e  piotecled  fiun 
cholera:  but  in  those  Avho  have  already  contracted  tln'  disease  the  prote< 
tive  intlnence  is  of  no  a\  ail  (  el".  §  ;>•_> ). 


On  gvl:itiii-plat(S  cultures  of  cholera-spirilla  form  roiuid,  llai. 
wliicli  liiiucfy  tlic  lidaliii  ouly  slowly.  At  a  low  iiiaunirualioii  tiu- 
ivuular  in  outline,  ami  of  a  granular  or  furrowed  and  rouirli  surface, 
strewn  with  small  particles  of  i«lass  (A"'W/).     ThrouL^ii  the  liquefactio 


yillowivh  disc- 
cultures  are  ir 
ippearing  iis  il 
clatii 


)f  Ml 


in  its  imnietliate  neighborhood  there  is  formed  a  funnel-sliaped  cavity,  to  the  boltom  ot 
which  the  colony  sinks. 

Stal)-cultures  in  gelatin  form  on  the  second  day  a  whitish  cord  correspoiuh'iiir  I. 
the  line  of  the  stal)  (I-'ig.  .)14),  in  the  iruinediate  neigiihorhood  of  wliieh  the  gelatin  i- 
licjuefiod.  The  canal  tluis  formed  widens  o\it  above  into  a  fuiuiol 
])art  which  is  filled  in  its  lower  portion  with  liquefied  gelatin  and 
in  its  upper  with  air.  The  widening  of  the  funnel  of  the  canal  of 
inoculation  takes  place  very  slowly,  so  .that  its  edge  reaches  the 
wall  of  the  tube  only  after  five  to  six  days. 

On  potatoes  at  "from  30°-35°  C.  the  spirilla  form  light-brown 
cultures,  on  agar-agar  grayish-yellow  slimy  cultures.  They  grow 
also  in  bouillon,  blood-serum,  and  milk. 

They  do  not  increase  in  pure  water  {Bolton),  but  do  so  in  water 
contaminated  with  substances  furnishing  nutrient  material. 

The  cholera-spirilla  are  aerobic,  but  they  are  also  abl.'  to 
grow  under  anaerobic  conditions.  According  to  investigations  by 
Htieppe,  cultivation  %x-ith  a  deficient  supi)ly  of  oxygen  increases  the 
virulence  of  the  culture:  but  the  resisting  jjower  against  injurious 
agents — for  example,  against  acids — is  on  the  other  hand  lowered; 
with  free  access  of  oxygen  the  reverse  takes  place.  P/'ciflcr,  how- 
ever, found  that  young  cultures  grown  in  the  presence  of  oxygen 
also  contained  poison.  The  spirilla  ])resent  in  fresi>  dejections 
(ffueppe)  are  easily  killed,  and  have  but  little  infecting  power; 
whereas  the  gi'owth  of  the  spirilla  outside  of  the  body  increases 
their  resistance  (for  example,  against  the  gastric  juice)  and  makes 
them  at  the  same  time  more  capable  of  causing  infection  in  new 
individuals.  They  are  easily  destroyed  by  desiccation  in  free  air 
(Guj/on)  and  by  high  temperatures,  and  by  boiling  for  a  short 
time.  They  are  easily  supjjlanted  by  sapro])hytic  bacteria  when 
the  nutrient  material  and  the  temperature  are  not  suitai)lc.  In 
the  contents  of  privy-vaults  they  soon  die  out  (Koch).  They  arc 
very  easily  killed  by  acids,  mercuric  chloride,  and  carl)olic  acid. 
According  to  observations  hy  Koch,  they  may  live  in  well  water  for 
thirty  days,  in  sewage  for  seven  days,  and  on  damp  linen  for  three 
to  four  days.  Xicatl  and  Reitsch  found  f  liem  alive  after  eiglity-one 
days  in  water  taken  from  iiie  harbor  of  Marseilles. 

In  cultures  they  sometimes  form  short  rods,  more  or  less  curvcii 
(Fig.  oVi)  and  often  joined  in  pairs;  at  otlier  times  they  form 
long  spirals.  With  these  there  also  occur  straight  rods,  and  oc- 
casionally the  majority  form  rods  which  show  the  curve  only  im- 
perfectly or  not  at  all  J 

At  a  certain  degree  of  exhaustion  of  the  food-material  there 
frequently  appear  involution  forms,  in  wliich  the  rods  are  some- 
times shrunken,  sometimes  swollen,  thus  creating  a  great  variety 
of  forms.  A  globular  swelling,  as  well  as  the  formation  of  spots 
which  do  not  take  the  stain  in  stained  preparations,  occurs  as  the 
result  of  degeneration,  and  have  often  been  erroneously  intcr|)rctcd 
as  phenomena  of  fructification.  Sjjore  formation  has  not  been  de- 
monstrated. The  addition  of  hydrochloric  or  sulphuric  acid  to 
cultures  of  cholera-spirilla  in  jieptone-containing  media  (|icplone- 
meat-infusion  or  an  alkaline,  oiie-i)er-cent  solution  of  peptone  containing  one  per 
cent  of  salt)  causes  tlie  culture  to  assvune  a  ro-^e-rctl  or  Hurgundy-rc<l  color,  due  to  ilu- 
4.'1 


KIC..5U.  Siiitw 
iiin-.  In  k'i'liiiiii, 
clioi«'ni->i>irillii. 


674  THE    PARASITIC    FISSION-FUNGI. 

formation  of  a  coloring-matter,  cholera-red.  According  to  Salkowski,  this  is  a  nitroso- 
indol  reaction. 

In  order  to  facilitate  the  separation  of  cholera-spirilla  from  other  intestinal  bacteria, 
Schottelius  recommends  the  mixing  of  the  dejecta  with  double  the  amount  of  a  shghtly 
alkaline  meat-infusion,  and  allowing  the  mixture  to  remain  uncovered  for  twelve  hours 
at  a  temperature  of  from  30°--40''  C.  The  spirilla  requiring  oxygen  will  develop  par- 
ticularly upon  the  surface,  and  may  be  easily  transferred  thence  to  plate-cultures. 
Koch  recommends  for  this  purpose  a  solution  of  peptone  with  common  salt. 

According  to  investigations  by  Nicati,  Rietsch,  van  Ermengem,  and  Koch,  symptoms 
resembling  cholera  may  be  produced  in  experimental  animals  through  tlie  introduction 
of  cholera-spirilla  into  the  intestinal  canal.  This  experiment  succeeds  wlien  cultures 
are  introduced  directly  into  the  duodenum  or  small  intestine  {Nicati  and  Rietsch);  as 
well  as  when  the  gastric  juice  of  the  animals  (guinea-pigs)  is  neutralized  with  a  five- 
per-cent  solution  of  soda,  the  bowels  being  quieted  by  an  injection  of  1  c.c.  of  tincture 
of  opium  to  every  200  gm.  of  the  body-weight,  and  one  or  more  drops  of  a  pure  culture 
of  the  spirilla  then  introduced  into  the  stomach  (Koch). 

The  animals  thus  inoculated  die  with  marked  sjanptoms  of  collapse.  The  small 
intestine  h  found  to  be  filled  with  a  watery,  flocculent,  colorless  fluid  containing  spirilla 
in  great  numbers;    the  intestinal  mucosa  is  reddened  and  swollen. 

The  poison  which  is  produced  by  the  cholera-bacillus  and  which  causes  the  essen- 
tial clinical  symptoms  of  a  cholera-infection  is  not  known.  Gamale'ia  believes  that  it 
is  a  nucleo-albumin;  Scholl,  that  it  is  a  peptone  (choleratoxopepton).  Pfciffer  is  of  the 
opinion  that  it  is  an  element  of  the  cell-body.  According  to  Metschniknff  and  others,  it 
is  secreted  by  the  cells.  According  to  Oppenheimer,  it  is  probably  an  endotoxin  which 
is  very  l.ibile  and  easily  passes  over  to  a  secondary  poisonous  mixture  rich  in  toxoids. 
Further,  the  spirilla  contain  a  bacterial  protein  which  is  not  specific  and  which  excites 
inflammation. 

The  virulence  of  cholera-cultures  differs  greatly,  according  to  the  place  of  origin  and 
the  age.  The  virulence  decreases  with  the  age.  Guinea-pigs  which  are  very  suscep- 
tible to  intraperitoneal  inoculations  of  cholera  may  be  protected  against  this  mfection 
by  tlie  intraperitoneal  injection  of  attenuated  cultiires;  but  no  absolute  innnuuity  can 
be  produced  in  this  way.  The  blood-serum  of  human  individuals  that  liave  recovered 
from  an  attack  of  cholera  shows  protective  properties  for  guinea-pigs  for  several  weeks 
after  tlie  attack. 

The  nitroso-indol  reaction  in  cultures  of  the  cholera-spirilla  is  due  to  the  fact  that 
the  cholera-spirillum  in  peptone  solutions  not  only  forms  indol  but  also  nitrites.  The 
addition  of  hydrochloric  or  sulphuric  acid  sets  free  nitrous  acid  which  forms  a  red  color 
with  indol.  With  the  Spirilliiui  of  FinMer,  the  Spirillum  of  3Ietschni/coff,  and  tlie  Spir- 
illam  (f  Deneke,  which  also  produce  indol,  the  red  color  of  the  cultures  occurs  only  when 
potassium  nitrite  is  added  with  sulphuric  acid,  or  when  nitrous  acid  alone  is  added. 


Spirilla  Resembling  the  Cholera=Spirillum. 

(1)  The  Spirillum  of  Finkler  and  Prior,  found  by  these  observers  in  the  dejecta  of 
persons  suffering  from  cholera-nostras,  after  the  discharges  have  stood  for  some  time  in 
a  vessel.  Tiie  spirilla  are  very  similar  to  tlie  cholera-spirilla,  only  somewhat  longer  and 
tliicker.  In  plate-cultures  they  are  distinguished  from  the  latter  only  in  the  fact  that 
the  small  colonies  are  not  distinctly  granular  and  have  a  sharp  contour.  Gelatin  is 
quickl}',  not  slowly,  liquefied;  and  consequently  in  stab-cultures  after  twenty-four 
hours  a  sac-like  tube  filled  with  cloudy  fluid  (Fig.  515)  is  formed,  which  soon  reaches 
the  walls  of  the  tube. 

On  potatoes  {Flicgge),  even  at  room  temperatures,  X\\ej  form  within  forty-eight 
hours  a  grayish -yellow,  slimy  coating,  sharply  marked  off  from  the  substance  of  the 
potato  by  a  whitish  border;  while  cholera-spirilla  do  not  grow  at  all  at  room-temper- 
ature, and  at  higher  temperatures  form  brown  coatings. 

Furtiier,  Ihey  cause  a  foul-sm<?lling  decomposition;  and  are  rather  resistant  to  dry- 
ing. When  introduced  into  tii(!  intestine  of  guinea-pigs  by  the  method  given  above, 
they  produce  effects  similar  to  tliose  caused  liy  cholera-spirilla,  but  less  intense. 

It  is  very  doubtful  wliether  the  Spirilluni  of  Finkler  and  Prior  possesses  a  patho- 
genic significance  for  cholera-nostras,  since  the  dejecta  from  which  these  investigators 
obtained  their  cultures  were  not  fresh  ;  and  other  authors  have  failed  to  find  the  spirilla  i 
in  corresponding  cases  (Kartuli.'^,  "Zur  Aetiologie  der  Cholera  nostras,"  Zeitschr.  f 
Ilyg.,  vi.,  1889).  Knisl  {^fi)nchener  (irztlic/ies  Inidligenzblatf,  1885),  on  tlie  other  hand, 
found  tliem  in  the  ciecal  contents  of  a  suicide. 


ASIATIC    CII()LKI{A. 


(3)  Spirillum  ti/rof/eninn.  found  ii 
vtfd.  Wor/i('ii}<ehr.,  1885),  is  also  very  i 
sii'.alU'r,  iiiid  the  loii<r  spiral  tliivadsai 
iircs  (in  .ii'ciatiii-platCs  form  at  first  si 
low  niaiiniticatioii  ai)i)car  dark,  and   1 


ut  d( 


)t  1) 


■lucsc  by  T>r»fkc  in  F'Uiggc's  Iiistiliilc  {Dnit. 

U(  h  like  tlio  cliolcm-spiriHiiin,  but  is  soiucwhul 

more  closi'ly   wound,    ("idt- 

rjily  conlourcd  discs  that  liy  \\mM_ 

li(pic'fv  lilt'  ixclatin   more    r;i|i-  J^'^^W^ 

slali-cultur.'s  Ihcy  bcliav.'  like.  '     '   " 

>t,  i^row  upon  poliito. 
rilluni  of  tlu;  siiaiic  of  a  curved 
tiian  the  ciioleraspirilUini.      ll 
euilivated  upon  the  ordinary 


idly  than  the  spirillum  of  K 
the  Finkler-Prior  spirillum, 

(B)  Spirilhnn  sputif/rmn 
rod,  somewhat  louij^er  and 
occurs  in  the  saliva,  and  e; 
media. 

(4)  Vi/>rio.  of  Mdsrhuikoxr  {Gainale„i,  "Vibrio  ^let.schnikovi  et 
ses  rapports  avecle  microbe  du  cholera  asialique."  vl////(^^  d  I'lUst 
Past.,  ii.,  1888;  iii.,  1889;  Ifeiffer,  "Ueber  den  Vibrio  Metseiuiikovi 
uud  seiu  Verhaltuiss  zur  Cholera  asiatica,"  Zeitxrhr.  f.  JIi/u..  18S!t) 
is  a  fission-fungus  isolated  by  Gamaleia  in  an  epidemic  ()ecurrini: 
in  chickens  in  Odessa,  wliich  Avas  chara(!terized  by  diarrho-a  anil 
enteritis.  When  cultivated  it  shows  a  very  great"  resemblance  to 
the  cholera-spirillum  of  Koch.  The  si)irill"um  is  most  easily  ol)- 
taiued  pure  by  inoculating  pigeons  with  the  blood  of  diseased 
chickens.  The  pigeons  die  in  from  twelve  to  twenty  hours  and 
show  the  spirilla  in  the  blood  and  in  the  intestinal  tract. 

ZiVgr^f?- has  transfernnl  Relapsing  Fever  to  the  protozoan  dis- 
eases, following  ^'(•/;'n^r/';'////'.s- view  tliattlic  spirocha'tesare  i)rotozoa. 
If  this  opinion  be  correct,  Syphilis  should  likewise  be  classed  with 
the  protozoan  infections.  As  mentioned  below,  the  correctness  of 
such  a  view  is  doubted  by  other  writers  (Av'jv/),  who  believe  that 
the  spirocluctes  are  bacterial  and  ai-e  to  be  classed  with  the  spirilla. 


W^'^ 


I'll..     .".l.'>.        Milli- 

ciiluirc.  ill  p'liilin, 
of  III.'  Siiililllliil  of 
Fiiihlir  and  I'rior. 


I.  I'.onii, 


Literature. 

(Sjjirillum  of  Asiutic  Cholera.) 

Barth:  Die  Cholera,  Breslau,  1893. 

Brieger:   Choleraroth.      Deut.    med.   Woch..    1887;   Stollwechsel 

producte  d.  Cholerabacillen.     Berl.  klin.  Woch.,  1887. 
Bujwid:  Chcm.  Keaction  f.  d.  Cholerabakt.     Zcitschr.  f.  IIvg.,ii., 

1887;  Cbl.  f.  Bakt.,  iii.,  1888. 
Dieudonne:  Uebersicht  iiber  die  choleraahnlichen  Vibrioncn.     Ci)l. 

f.  Bakt.,xvi.,  1894. 
Dunbar:    Dilleicntialdiagnose    zw.    Choleravibr.     u.    and.    Vibr. 

Zcitschr.  f.  llyg.,  x.xi.,  1896. 
van   Ermengem:   Eech.   sur   le    microbe    du   cholera    asiatiipie, 

Ihu.xellcs.  18So;  Neue  Untersuchungen  uber  Choleramikrobeii. 

Wien.  1886. 
Finkleru.  Prior.  Deut.  med.  'Wocli.,  1884;  Forschungcn  iili.  Cliolcrabak 

188(). 
Fliigge:  Verbreitungsweise  u.  Verlilltung  d.  Cholera.     Zcitschr.   f.  llyg.,    \iv.,  IS'.K!. 
Fraenkel;  Choleraleichenbefunde.     Deut.  med.  AVoch.,   1893. 

Galeotti:  Immunitat  u.  Bakteriotherapicge.gen  Cliolera.    Cbl.  f.ailg.  l'ath..l>9r>  (Lii.i. 
Gamaleia:  Ueeh.  exper.  sur  les  poisons  du  cholera.  Arch,  de  ni(5d.  exp..  iv..  isjia. 
Hesse:  Nahrungsmittel  als  Niihrboden  f.  Typhus  u.  Cholera.     Zcitschr.  f.   Hyg.,  v., 

1889. 
Hueppe:  Dauerformen  d.  Cholerabacillen.     Fortschr.  d.  :Med.,  iii..  \m:>\  (Jifligkeit  d. 

Cholerabakterien.     Deut.   med.   Woch.,   1889;  Aetiologie  d.   Cholera.     B-rl.   klin. 

Woch.,  1890;  Aetiol.  u.   Toxikol.  d.  Cholera.     Deut.  med.  Woch..  1S!»|  ;  Die  Choi- 

eraepidemie  in  Hamburg,  1893,  Berlin,  bS9:l 
Kitasato:  Widerstandsfilhigkeit   d.    Cholerabakterien   gegen   Einlrockiicn    u.    Ilil/.e. 

Zcitschr.  f.   Hyg.,  v.,  vi.  ;  Verhalten  d.  Cholerabakterien  iin  mcnschl.  Koih   u.  in 

Milch.     II).,  v.,  1889. 
Koch:  Aetiologie  d.  Cholera.     Deut.  Vierteljahrssciir.  f.  olT.  Gesundhcilsptlcge,  xvi., 

1884;  Conferenz  z.   Erorterung  der  Cholerafrage.     Deut.   med.    Wocli..   IH«4-«<5; 

Choleradiagnose.     Zcitschr.  f.  Ilvg.,  xiv.,  1893;  Die  Ciioleru  in  DeulHcidund  wflh- 

rend  des  Winti-rs,  189-3-93.     lb,,"xv.,  1893. 
Koch  II.  GafFky:  Bcricht   iiber  die  Tliiltigkeit  der  /,.  Erforschung  il.  Cliolcni  im    .1 


676  THE    PARASITIC    FISSION-FUNGI. 

1883  nach  Aeijj-pten  u.  Indicn  entsandten  Commission.      Arb.  a.  d.  K.  (t.-A.,   iii., 

1887. 
Kolle:  Cholera  asiatica.     Handb.  d.  patliog.  Mikroorg.,  iii.,  Jena,  1903  (Lit.). 
]>IetschnikofF:  Toxine  et  antitoxine  choleiique.     xVnn.  de  I'lusT.  Pasteur,  1896. 
Neuhaus:  Ueber  die  Geisseln  an  den  Bacillen  der  asiat.  Cholera.       Cbl.  f.  Bakt.,  v., 

INN!). 
Nicati  et  Rietsch:  liecli.  sur  le  cholera,  Paris,  1886. 
V.  Pettenkofer:  Stand  der  Cholerafrage.     Arch.  f.  Hyg.,  v.,  vi.,  vii.,  1887;  Der  epi- 

deniiologische  Theil  des  Berichtes  iiber  die  Thatigkeit  der  zur  Erforschung  der 

Cholera  ini  .Tahre  1883  nach  Aegypten  nnd  Indien  entsandten  Commission.  Miinchen 

u.  Leipzig,  1888;  Ueber  Cholera.     Miinch.   med.  Woch.,  1892.     Cbl.  f.  Bakt.,  xii., 

1N92. 
Pfeiffer:  Choleragift.     Zeitschr.  f.  Hvg.,  xi.,  1892;  Antikorper  d.  Cholera.     lb.,  xx., 

INli.-,. 
Riedel:  Dii-  Cholera,  Entstelmng,  Wesen  u.  Verhutung  derselbeu,  Berlin,  1887. 
Rumpf:  Die  Clinli  ra  :isi;ili(;i  ii.  nostras,  Jena,  1898. 

Rumpf  11.  Galfky  :   Wu-  (  lidlcra.     Verb.  d.  XIL  Congr.  f.  inn.  Med.,  Wiesbaden,  1893. 
Salkowski:   LcIk  r  da^  ( 'hoh  raidth.      Vireii.  Arch.,  110  Bd.,  1887. 
Scholl:  I'ntcrs.  iiber  -iftiuc  Liwcisskinper  bei  Cholera.      Arch.  f.  Hyg.,  xv.,  1892. 
Schottelius:  Naeliwcis  der  (  Jiolerahac.  in  den  Dejeetioneii.     Deut.  med.  Woch.,  1885, 

1SS9. 
Schuchardt:  Ueber  das  Choleraroth.     Vircb.  Arch.,  110  Bd..  1887. 
Sobernheini:  Choleraimmuuitat.     Zeitschr.  f.  Hyg.,  xx.,  1895. 
Stieda:  Neiie  Arbeiten  iiber  Cholera  asiatica.     Cbl.  f.  allg.  Path.,  iv.,  1893. 
Tizzoni  et  Cattani:  Keeli.  siir  le  cholera  asiatique.     Beitr.  v.  Ziegler,  iii.,  1888. 
Tsehistowitsch :  Veriind.  d.  Gehirns  bei  Cholera.     Virch.  Arch.,  144  Bd.,  1896. 
Voges:  Die  Cholerainmumitat.     Cbl.  f.  Bakt.,  xix.,  1896  (Lit.). 


CHAPTER  XI. 

The  Yeasts  and  floulds,  and  the  Diseases  Caused  by 

Them. 

§  180.  The  yeasts  (Blastomycetes;  and  the  moulds  i  Hyphomycetes) 
beloug,  as  do  the  schizomycetes,  to  the  iion-chl«»ii>i»li_\  llaccuiis  tliall<>- 
phytes.  AVitli  the  schizoinyceles  they  liave  no  phylo.m'iu'tic  ichiliunsliii. : 
on  the  other  hand,  they  are  closely  lelatcd  to  om-  annilici-.  and  Ix.ih  1m-- 
loug  to  the  branchinji-  fungi  or  the  euniyeetes. 

The  moulds  and  yeasts,  like  the  sehi/.omyeeles,  d('ri\  »■  ihcir  ii..iiri>li- 
luent  from  organic  substances  containing  carbon.  The  niajoiitN  tiiid 
their  food  in  dead  organic  substances,  and  belong  llicrclorr  lu  iht-  .s,ii„n 
phytes ;  some  are  able  to  obtain  nourishment  fiom  li\  ing  tissnes.  and  arc 
to  be  classed,  at  least  at  times,  -with  X\\i^ ponisiti's.  in  human  b<'ings  both 
forms  occur. 

Outside  the  organism  the  moulds  ar<'  generally  known  ;in  iIh-  ihm- 
ducers  of  the  different  mouldy  lilms  which  so  fi(M|iiciitly  dc\  cln|.  npon 
orgauic  substances.     Tliey  belong  to  ditfiTcnt  gioups  of  iungi. 

The  yeast-fungi  are  the  cause  of  alcoholic  fernuMitation,  and  form  the 
scum  on  the  top  of  alcoholic  beverages. 

Literature. 

{M,nil(h  (in(J  Yra.sts.) 

De  Bary,  A.:  Vergl.  Moiijhologie  d.  Biologic  d.  Pilze,  .Mvcotozoon  ii.  Haktcricn.  I,i'i|)- 
zii:,  18S4. 

Brefeld:  Inters,  aus  dem  Gesammtgebiete  der  Mykologie,  Heft  i.  x..  Lcip/ii;.  Is7t  '.'1. 

Feinberg:  Ban  der  Hefezellen.     Ber.  d.  D.  hot.  (Jes..  xx.,  litOJ. 

Janssens;  T'eber  den  Kern  der  Hefezellen.     Chi.  f.  Bakt.,  xiii..  IS'.C). 

Jorg-ensen:   Die  Mikroorganismen  der  Gahrungsindustrie.  Berlin.  IS'.rj. 

Koch:  Jahrcsher.  iiber  die  Fortschritte  der  Lehre  von  den  GalH-'inirsnriranisiiicn.  Is'.td- 
j  1904. 

I        Plaut:    Die  Hvphenpilze  oder  Eunivceten.     Handh.  d.  path.  Mikroor-r..  i.,  .Icn.-i.   I'.MKJ 
!  (Lit.).       ' 

Raum:   Ziir  Morpliologie  u.  Biologic  der  Spros.spilze.     Zeit.schr.  f.  Ilyg..  x..  IMM. 

Tavel:    \ri<rl.'i<'h.Midp  .Morj^holoiiie  der  Pil/e.  Jena,    l.sn2. 

Uhlworm  u.  Hansen:  Chi.  f.  Bakt.,  ii.  .Vl>th..  Bd.  l-().  .Jena,  IS'.r, -I'.MM. 

Zopf:  Die  Tilze.     Handh.  d.  Botanik  v.  .Sclienk,  iv. 

§  181.  Yeasts  occnr  in  man  in  the  form  of  iid/.rtl  or  ninipsuhit,,!,  ontl 
or  roiDid  cells  nl'  varying  size.  They  aic  found  cliielly  as  liarmlos  sapro- 
phytes, most  freijuently  in  the  upiM'f  part  of  llie  intestinal  canal  -  iu  llie 
stomach — where  they  are  almost  constantly  present  :  ami  when  beverages 
in  the  pi-ocess  of  alcoholic  feiin<'ntati(tn  are  taken  they  ma.\  occur  iu 
large  nnnd^ers,  and  may  also  lunlliply.  In  the  bladder  they  m:iy  like- 
wise multiply,  in  case  tlie  urine  contains  sugar;  and  nia\  cause  fermen- 
tation of  the  urine  with  evolution  of  carbonic-acid  gas. 

As  parasites  no  importance  has  been  allachcd  to  them  until  \eiy 
recently,  but  the  investigations  of  I'.usse.   Buschke,  Sanlelice.  Cnrlis.  and 


678 


THE    PATHOGENIC    YEASTS    AXD    MOULDS. 


Fig.  516.  —SacclKi- 
rnmyces  ellipsoideus. 
X  400. 


others  liaxe  establislied  the  fact  that  there  are  also  species  of  Saccharo- 

myretes  of  pathixjenic   iinportance.     According  to  these  observations  the 

pathogenic  yeasts  can  multiply  in  different  tissues,  in 

the  skin,  ijeriosteum,  lungs,  and  glandular  organs,  and 

can  excite  either  purulent  inflammations,  or  prot if erations 

of  granulation  tissue,  which  run  a  course  similar  to  that 

of  an  infection  with  actinomycosis  or  tuberculosis.     In 

inflammatory  foci  the  yeast  cells  are  for  the  chief  part 

provided  with  a  capsule.     They  may  be  present  in  large 

numbers  so  that  through  their  mass  alone  they  may  give 

rise    to   tumor-like   swellings.     Through   degenerative 

changes,  crescentic  forms  may  develop  from  the  oval 

yeast-cells. 

In  solutions  containing  sugar  the  blastomycetes  form  oval  cells  (Fig. 

51()  j.  Reproduction  takes  place  through  budding  and  constriction ;  on 
any  portion  of  the  parent  cell  there  may 
develop  an  excrescence,  which  is  constrict- 
ed off  after  it  reaches  the  size  of  the  mother  \ 
cell.  Under  certain  conditions  the  cells 
may  grow  out  into  threads  or  hyphae,  but 
in  these  threads  no  subsequent  segmenta- 
tion occur;  jointed  threads  arise  through 
budding.  A  dilute  culture-medium  favors 
the  formation  of  tlireads. 

nould=fungi  are  found  in  man  partly 
in  the  form  of   simple   or   branched,  un 
jointed  or  jointed  threads  of  varying  thick- 
ness;   and   partly   as   oblong   or    even    as 
spherical   cells.      The  threads  are    desig- 
nated as  hyphae  (Figs.  517,  518),   and  the 
mass  which  they  form  as  mycelium;  the' 
spherical  or  long  oval  or  short  cylindrical 
cells,  which  are  frequently  arranged  in  the ;( 
form  of  a  rosary,    as  spores,   or  better   asJE; 
conidia=spores  (Figs.  517,  51.S;.  Only  rare- 
ly has  there  been  observed  witliin  the  body 
a  fructification  upon  special  fruit-organs. 
The  moulds  are  partly  saprophytes  and  partly  parasites ;  and  are 

found  ahnost  exclusively  in  regions  accessi- 
ble  from  without,   as  the   skin,    intestinal 

canal,  respiratory  tract,  external  ear,  vagina, 

etc.     Only  exceptionally,  and  under  especial 

conditions,  do  they  reach  the  internal  organs, 

as,  for  example,  the  brain.    It  is  evident  that, 

on  the  whole,  the  living  tissues  of  the  human 

organism  do  not  afford  a  suitjijjle  nutrient 

medium  for  the  mould-fungi,  and  the  life- 
activities  of  the  tissue-cells  for  tlie  greater 

part  do  not  permit  their  development  and 

limit ii>licat ion.      The  need  for  oxygen  pre- 

Aciits  tlic  growth  of  moulds  in  many  tissues; 

and  for  many  moulds  tlie  temperature  of  the 

body  is  too  liigh.     Moreovei',  tlie  chemical  composition  of  the  tissues 


Fig.  517.— Fresh  favus-mass  consist- 
ing of  hypba?.  conidia,  and  epithelial 
cells.    (After  Neumann.) 


Fig.  518.— From  a  growth  of  thrushl 
on  the  toncrue  of  a  man  dying  of  ty-'| 
phoid  fever.      >;  275. 


does  not  olfer  to  the  moulds  a  favoi-able  mixture  of  nutrient  material. 


SAPKOIMI  Yl'[('    MOILDS. 


Moulds  growing  as  saprophytes  m-vuv  in  nuiii  iiiosr  fiv(|ii('iitly  in 
the  aliuu'iitai y  eaiial,  i»ailicMilarly  in  tiic  inoiit/i,  jt/iari/ii.r,  and //■.s<>/^/hj////.s. 
They  (U'vclop  in  tlu'st'  regions  paiticnlaily  wlicn  lli<'  inj;«'sla  or  dcsqna- 
matod  colls  lie  undistnrbcd  in  one  jxtsition  for  a  lon.<i-  lime,  and  wlicn  llin 
function  of  thcor,<;aii  concerned  is  lowered.  They  are  icco^ni/ed  lliron^ii 
the  forniation  of  hyphnc  and  conidia. 

In  tlie  external  auditonj  cunul  monlds  i;ro\v  especiallv  in  almornial 
masses  which  till  up  the  ])assa,<;e  and  coHsist  in  ]»art  of  (cinnien,  or  of 
inttaniiiiatory  exudates  and  desquanuded  cells,  and  in  pari  of  snl»stanees 
introduced  from  without. 

In  the /(///r/,s  uu)ulds  are  occasionall\  tonnd  u|»on  the  necroiir  wull  oi' 
cavities,  particularly  those  due  to  tul)ei'cnl(»is,  as  well  as  in  necrotic  and 
gangrenous  Im^iuorrhagic  infarcts,  etc.  Jn  the  air-passages  tiiey  are 
observed  most  frequently  in  bronchiectases. 

In  the  alimentary  tract,  as  well  as  in  the  ear  and  lungs,  tlie  moulds 
form  chiefly  a  Avhitisli  deposit  on  or  in  the  tissues.  Jn  the  event  of  fruc- 
tification upon  especial  fiuit-bearers  they  may  take  on  a  brown,  gray,  or 
even  black  appearance.  In  the  intestinal  canal  the  food  and  driid<  may 
give  them  vaiious  colors. 

At  first  the  moulds  grow  in  dead  nuiterial,  but  they  may  penetrate 
thence  more  or  less  extensively  into  living  tissue;  and  cases  have  i»'eii 
observed  in  which  they  have  even  entered  the  cii-culatictn  and  ha\<'  been 


Fio.  519. — Section  tlirouKli  a  thiusli-covcrcd  ii-sopliaKUs  of  a  small  <liilil  (alcoliol,  larinitif,  (irnin's). 
o.  Connective  tis.sue ;  /j,  normal  epitlieliuni;  c,  swollen  anil  desquamated  epitliflliiin  inlllli-ut<'il  wllli  fuii- 
Kus-tlireads  ;  (f,  epithelium  inQltrated  with  cells;  c,  cocci  and  bacilli ; /,  cellular  fiM'iis  In  the  connective 


carried  by  the  blood-stream  to  distant  organs.  Thus  the  tniigons  grow  Ih 
called  thrush  which  a])pears  chielly  upon  the  mucous  membrane  of  tlu' 
iiionIJi,  jili<iri/ii.r,  and  a'.s()jt/i<(f/us,  and  more  rarely  up(Ui  that  of  the  shnnorh, 
infc.sliiir,  A\\(\  rof/iiKi,  and  upon  the  iiljijths  ttl'  nursing  women,  cannot  be 
regarded  as  a  i)ur(!  sajn'ophyt  ic,  but,  on  the  contrary,  i^  a  parasitic 
growth,  which  i)enetrates  into  living  epithelium  (l-'ig.  .".1!>,  >■).  aii<l  ex.-n 
into  the  underlying  connective  tissue.  It  is  true,  howexcr.  tlial  thrush 
occurs  chiefly  in  infants  and  in  debilitated  iinalids  who  are  no  longer 
al)le  to  cleanse  the  mouth,  throat,  and  U'sojjhagus,  so  that  some  i-special 
local  i)]'edisposition  appears  to  be  necessary  for  its  d<'\ clopment.  and  it. 
is  probal)le  that  the  primary  colonization  of  IIm-  fungus  takes  place  in 
dead    material.     Xevertheless,  there  occurs  then  an  active  peiictiaiion 


f)SO  THE    PATHOGENIC    YEASTS    AND    AIOILDS. 

into  livjiio-  tissue — that  is,  first  into  the  epithelium  (r,  d),  but  often  alx* 
into  the  eonuective  tissue  («,/),  and  into  tlie  blood-vessels,  and  from 
these  poi'tals  of  invasion  there  may  develop  metastases  in  the  internal 
orgaUvS.  Thus,  Zenker  has  observed  hypha'  and  oonidia  in  an  abscess  of 
the  brain;  and  Paltauf  has  reported  a  ease  in  which  a  mould- fungus  Avas 
conveyed  from  an  intestinal  ulcer  to  the  brain  and  lung.  Schmorl  and 
Heubuer  have  described  thrush-metastases  in  the  kidneys. 

[Moreover,  growths  of  moulds  in  the  lungs  are  not  alw  ays  confined  to 
dead  material  or  to  the  cavity  of  the  bronchus,  but  it  hai)pens,  though 
rarely,  that  they  penetrate  into  the  living  respiratoiy  pai-enchyma,  form- 
ing small  white  or  yellowish,  nodular  masses,  within  which  the  lung  tissue 
is  necrotic,  while  in  the  neighborhood  there  is  formed  an  inflammatory 
infiltration.  In  the  injured  cornea  they  may  likewise  penetrate  into  the 
tissue  and  cause  necrosis  and  inflammation. 

Local  colonizations  of  moulds  which  penetrate  into  living  tissue 
cause  a  more  or  less  marked  irritation  of  the  sunuunding  tissues,  and 
give  rise  to  tissue-degenerations  (Fig.  519,  e)  and  injfammation.  Such 
changes  may  be  observed  in  mycosis  of  the  lung,  as  well  as  of  the  intes- 
tine (e,  d,f)  and  ear.  "WTien  invading  the  lungs  they  form  growths  of 
hyphae  which  resemble  the  granules  of  actinomycosis,  and  are  surrounde<l 
by  collections  of  cells.  Their  action,  however,  is  always  limited,  and 
they  produce  no  substances  which  are  injurious  to  the  organism  as  a  whole, 
or  cause  symptoms  of  poisoning.  The  frequently  reported  finding  of 
moulds  in  abscesses  of  the  subcutaneous  tissues  and  internal  organs  are 
probably  to  be  interpreted  as  due  to  the  fact,  that  along  with  the  bac- 
teria causing  the  suppuration,  moulds  also  get  into  the  tissues,  as  well 
as  into  the  circulation.  A  general  spreading  of  mould-fungi  does  not 
occur  in  these  cases,  in  that  the  further  development  of  the  same  is  con- 
fined to  the  place  of  the  metastasis. 

The  moulds  which  are  saprophytic,  or  are  to  a  limited  extent 
parasitic  in  man,  belong  to  the  Mucor,  Aspergillus,  and  Eurotium  gen- 
era. From  the  ear  various  species  have  Ix-eii  ol^tained:  AsporgUhtsfumi- 
f/atus  (Fresen),  AspergilJus  Jiavns  or  fJaveseens  (Brefeld,  Wreden ),  As- 
pergilJiis  niger  ov  »/(7;/w«.s' (Van  Tieghem,  AVreden,  AVilhelm),  ^ispergiUus 
niduJans  (Eidam),  Eurotium  maJignum  (Liiidt),  Mucor  cori/inhifer,  and 
Trichothecium  rose  urn  ;  and,  in  so  far  as  known,  these  are  the  same  species 
which  occasionally  occur  in  the  respiratory  tract. 

In  the  majority  of  cases  it  is  necessary,  in  order  to  determine  the 
variety  of  mould,  to  make  cultures  uijon  suitable  nutrient  media  (decoc- 
tion of  bread,  bread-agar,  potato,  gelatin,  etc.).  On  these  the  conidia 
which  are  sown  gi-ow  out  into  germ-tubes,  and  form  simple  or  branched, 
unicellular  or  multicellular  threads,  on  wliich  arise  the  peculiarly  con- 
structed fniit-bearers  characteristic  of  the  species,  which  eventually  pro- 
<luce  conidia.  Many  also  form  spores  through  the  copulation  of  cells  of 
the  mycelia,  especially  when  the  su])i)ly  of  oxygen  is  lowered  (Brefeld, 
Siebemnann). 

In  the  mucors  there  appear  especial //v/zV-iwrr/.s' (Fig.  520,  <?),  which 
according  to  the  species  are  either  single  or  branched,  and  on  the  ends  of 
which  there  are  knob-like  swellings  from  which  the  sporangia  (d) — that 
is,  spherical  vesicles  filled  Mith  conidia-siKucs — grow. 

Mucor  corgmhifer,  foi-  exami)]e,  forms  branched  fruit-bearers  (Fig. 
520,  c).  The  sporangia  (d)  on  the  ends  possess  a  smooth  membrane  arid 
enclose  at  the  time  of  lipening  yellowish  conidia-spores. 


TlllxM   Sll, 


(is  I 


Fig.  520.— "\/i((i)/  (onitiihtto  in  friictitlcation  (ciiltiiix'  tipi 
plass-sluic) .  (I,  Aci  lal  li vpli.f ;  '»,  iiiyi'i'lia  Ivintr  within  tlif  niiti 
entgelatm;  t,  liiaucUiug  f i uit-bearers ;  c/,  spurangia.     >    Km 


The  aspergilli  formconidia-bcanr.s,  whU-h  swell  out  sphei'iciilly  ahuvc. 
and  then  produce  nunierons  sirr'njmatit — that   is.   eoiie-like  oul;:;ro\\  llis, 

I'adially  anaii^cd,    lliickly 
\d  fl  crowded.      and     spmulin-i 

out  Iroiii  the  upper  liall' 
of  tiic  sphere.  V\u\\\  riicli 
sU'rijiiiia  a  vhaiu  of  fonldln 
is  later  const  liclcd  oil'  (  i-'ii;. 
521,  a,  h). 

The  h()f<inir<i/  jKt.silinii  of' 
llif  finit/Ks  of  l/inix/i  is  still 
unsettled.  "  Forineily  it 
was  called  Oidium  albi- 
cans, and  classed  with  the 
i;('iius  Oi'diinii,  which  oc- 
curs in  dillereut  species  in 
the  I'onn  of  liliiiy  eo:it- 
injis  ni)on  or.uauic  sul» 
stances.  When  culli\ated 
from  conidia  it  ])i-oduces 
hyi)lne  ^vhich  l)ecoine 
jointed  and  de\elop  coin- 
dia  through  a  transverse  division  of  the  threads,  but  form  no  peculiar 
fruit-bearers. 

According  to  Rees,  Grawitz,  Kehrer,  the  thrush-iiiiigns  grows  by 
budding  and  by  the  production  of  mycelia  and  (tonidia,  which  in  turn 
produce  at  their  ends,  by  a  process  of  constriction,  new  conidia.  in  a 
manner  similar  to  that  which  takes  place  in  the  loiins  of  mycoderma 
belonging  to  the  yeast-fungi. 
Cousecpiently  this  fungus  should 
be  designated  Mycoderma  albi- 
cans. Linossier  and  lioux  are, 
however,  of  the  opinion  that  the 
thrush-fungus  does  not  belong 
at  all  to  the  saccharoniycetes, 
and  they  regard  its  classification 
at  the  present  time  as  impossi- 
ble. Cao,  who  has  in\-estigated 
numerous  vay'uiicH  of  oiditnn,  re- 
gards the  oidia  as  a  well-defined 
class  of  fungi  standing  between 
the  blastomycetes  and  the  hy- 
phomycetes,  which  they  ap- 
])roach through  tlieir  ])i<)duction 
of  mycelia. 

According    to    Plant    1h<', 
thrush-fungus  is  identical   with  a  nn)ul<l.  J^/////"  iiiii(lid<i.    whieh   <M<ins 
frequently  in  nature.     Kehi-er  suspects  that  it  is  one  of  tlie  hi-her  nionhls 
which  has  become  degenerated  through  parasitism. 

According  to  ^^ell mai/ev  iiW  mr«V7/V.-<  o/' //*'<^v^^  arc  rcsistaiil  to  tlic  'lig'-dv  .i'liccs, 
and  may  pass  through  the  liuman  intestinal  trad,  witlioiit  iHln-r  Uillr.l.  ">''"""  •'"' 
coincident  introduction  of  some  tVrmcntaliii'  siiltstancc  tlicy  arc  iiarmli'ss.  I  liev  ••\crt 
an  influence  upon  the  intestinal  canal  only  when  fcrmciitalilcsnhslanecs  arr  mtroiliiced. 
whereby  at  the  higli  temperatme  of  the  body  at)normal  products  ot  Icrnicniatioii  are 
produced  having  an  h-ritating  action  upon  the  intestinal  tract. 


Fir.,  rc'l.-  nvpliuMViUi  .•oMi.lla-l.«-arci>..f  .1.-/..  ;■./(/'»<■» 
fiiniif/atus.  a.  I'nill-ln'ad  In  (.pili-al  in.ss-.H.iiinn  ;  /<, 
fiiiil-iii-ail  seen  from  utiove.     X  275. 


082  THE   PATHOGENIC    YEASTS   AND    MOULDS. 

Busse  found  (1894)  great  numbers  of  yeast-ceiis  developing  in  the  diseased  areas 
present  in  a  woman,  thirtj'-one  years  of  age,  who  died  from  multiple  inflammations  of 
the  bones,  skin ,  lungs,  kidneys,  and  spleen,  partly  tumor-like  and  partly  abscess-forming. 
According  to  his  findings  it  may  be  regarded  as  certain  that  the  yeast  was  the  cause  of 
the  disease.  The  yeast  could  be  easily  cultivated  upon  suitable  media.  Mice  were 
particularly  susceptil)le  to  inoculation,  dying  in  from  four  to  eighty-three  days  after  the 
injection.  '  At  death  the  yeast-cells  were  found  to  have  markedly  increased  both  at 
the  point  of  inoculation,  and  also  in  the  internal  organs.  A  proliferation  of  tissue 
occurred  only  after  a  long  duration  of  the  infection. 

/i(/sc/(/>e' found  yeasts  in  multiple  ulcers  of  head  and  neck,  arising  from  acne-like 
lesions.  Gilchrist  and  Stokes  found  yeasts  in  a  lupus-like  affection  of  the  skin.  Loicen- 
bach  and  Oppepheim  found  a  yeast  in  the  skin  of  the  nose  shewing  formation  of  nodules 
and  scar-tissue. 

In  1896  Gilchrist  reported  observations  on  a  peculiar  progressive  affection  of  the 
skin  characterized  by  epithelial  hyperplasia,  miliarj'  abscesses,  and  infiltration  of  the  cutis. 
In  the  abscesses  doubly-contoured  refractive,  roiind  and  oval  bodies  were  found.  They 
varied  in  size  from  10-20  ;t  and  presented  buds  of  varj'ing  size.  To  this  organism  the 
name  of  Blastomyces  dermatitidis  was  given,  and  the  skin  condition  was  called  blasto- 
mycetic  dermatitis.  About  fifty  cases  of  this  kind  have  since  been  reported,  the  majority 
of  them  by  Chicago  observers.  In  some  of  the  cases  a  fatal  generalized  infection  has 
been  seen.  The  organisms  cultivated  from  the  cases  fall  into  three  groups:  1,  a  blasto- 
mycetoid;  2,  an  oidium-like;  and  3,  a  hyphomycetoid  group.  According  to  Ricketts 
they  may  be  included  in  a  common  genus,  Oidium,  and  he  has  proposed  the  term 
oidiomycosis  for  the  various  lesions  produced  by  these  organisms.  At  the  present  time 
the  exact  botanical  classification  of  the  latter  is  not  possible. 

Under  the  designation  of  coccidioidal  granuloma  there  have  been  reported  eighteen 
cases  (fourteen  of  these  known  to  have  lived  in  California)  of  a  condition  closely  re- 
sembling oidiomycosis,  but  apparently  differing  from  it  in  certain  clinical  characteristics 
and  in  the  nature  of  the  organisms  found  in  the  lesions.  It  runs  a  more  severe  and 
progressive  course  than  the  latter  condition,  and  generalized  infection  is  the  rule.  The 
organism  multiplies  by  endogenous  sporulation  instead  of  by  budding.  Ophiils  would 
class  it  with  the  oidia  under  the  name  of  Oidium  coccidioides.  The  lesions  produced 
by  it  resemble  tubercles  closely  in  the  majority  of  cases,  and  clinically  the  disease  has 
been  mistaken  for  tuberculosis. 

Sanfelice  experimented  with  yeasts  from  fruit-juices,  and  found  among  these  one 
pathogenic  for  guinea-pigs  {Saccharomyces  neoformans)  and  one  pathogenic  for  chickens 
and  dogs  {Saccharomyces  Uthogenes).  Curtis  found,  in  multiple  proliferations  of  the 
skin  resembling  myxosarcoma,  yeast-cells  which  were  pathogenic  for  mice,  rats,  and 
dogs.  Cohn,  who  experimented  with  the  yeast  described  by  Klein,  found  that  its 
inoculation  into  the  peritoneal  cavity  of  mice  caused  death  through  the  fonnation  of 
great  yeast-tumors.  The  intravenous  infection  of  larger  animals  led  to  severe  dis- 
turbances of  brain  and  spinal  cord,  associated  with  inflammation  of  the  mucous  mem- 
branes, particularly  of  the  conjunctiva. 

Sanfelice,  Corselli,  Frisco,  Roncali,  Binaghi,  Leopold,  and  others  believe  that  blasto- 
mycetes  may  be  the  cause  of  true  tumors,  sarcoma  and  carcinoma;  but  true  tumors  have  j'l 
never  yet  been  produced  experimentally  by  inoculations  of  yeast-cells  or  by  injections Jh 
of  the  same  into  the  blood.  Only  supp\irations  and  inflammatoiy  tissue-proliferations|< 
have  been  produced  by  such  experiments;  and  the  finding  of  yeast-like  structures  inj 
true  tumors,  even  if  part  of  these  were  true  yeast-cells,  does  not  permit  of  the  conclusion 
that  tumors  are  caused  by  yeasts. 

According  to  investigations  by  Koch,  Loffler,  Lichtheim,  Hilckel,  and  Lindt,  the 
conidia  of  Aspergillus  fumigatus,  A.  flavescens,  A.  nidulans,  Ewotium  malignum,,  Mu 
cor  rhizopodiformis,  M.  corymbifer,  M.  pusillus,  and  M.  ramos^lS,  grow  at  the  body 
temperature,  and,  when  introduced  into  the  blood-current  of  animals,  grow  into  the 
tissues  and  form  hyphte,  although  there  isno  new-formation  of  conidia,  and  consequently 
no  progressive  infection  of  the  animal  extending  bej^ond  the  area  within  which  the  spores 
have  been  introduced.     Conidia  of  Mucor  rhizopodiformis  and  M.  corymbifer  grow, 
when  introduced  into  the  blood-stream  of  rabbits,  chiefly  in  the  kidneys  and  the  lym-  ."j 
jjhatic  apparatus  of  the  intestines,  where  they  cause  a  ha}morrhagic  inflammation,  j 
According  to  Cao,  there  are  <lifferent  species  of  oidia  which,  when  injected  into  rabbitS;.'* 
cause  inflammations,  abscesses,  or  proliferations  of  granulation  tissue;    and  many  pro- 
duce also  a  toxic  action  upon  the  organism. 

According  to  Ceni,  Aspergillus  fumigatus  which  grows  at  summer  temperature  pro- 
duces poisons  in  its  conidia.  One  of  these  can  be  extracted  with  alcohol  and  causes 
tetanic  convulsions  m  experimental  animals.  The  aspergillus  growing  upori  corn  plays 
an  important  role  in  the  etiology  of  pellagra. 

Aspergillus  mycoses  of  the  respiratory  tract  are  not  rare  in  animals,  espe- 


-I 


I 


ASPERGILLIS.  683 

cially  in  birds,  and  the  proliferating  inye^lia  cause  tissue-necrosis  and  inflammation. 
According  to  Chantemesse,  Aspen/ill  us  J'umigatuf!  causes  in  itigeons  diseased  cimditiim.s 
of  the  mouth,  lungs,  liver,  ami  kidney,  that  of  tlie  (irst  two  organs  resembling  .liph- 
theria,  that  of  the  latter  two  closely  resembling  tuberculosis.  It  may,  therefore,  bo 
designated  pscudotubcn-ulosis  asprn/illiua.  According  to  l*o(<n'n,  the  infection  maybe 
transmitted  to  man  and  give  rise  to  ulcerative  diseases  of  the  lung. 

Euroiium  and  Aspergillus,  according  to  Sicbcnmann,  are  two  different  families, 
having,  however,  a  close  resemblance  to  each  other,  in  that  the  mycelia  and  conidia  are 
similarly  formed.  The  essential  differences  between  the  two  lie  in  tlie  fact  that  huro- 
tium  produces  perithecia  in  the  form  of  shining,  light-yellow  or  sulphur-vellow.  translu- 
cent bodies  the  size  of  agrainof  sand,  delicateand easily  crushed,  and  wliich  ultimately 
develop  into  spores  capable  of  germination;  while  the  true  AspayiUus  forms  hard, 
woody  sclerotia  usually  embedded  in  a  thick,  white  matted  massOf  myceiia.  The 
development  of  these  takes  place  in  two  jjeriods.  The  second  |)art  of  the  deveh-pnient 
occurs  only  when  the  scleroiium  fimb  a  lodgment  upon  a  moist  substratum. 

Aspergillus  flavus  of  Brefeld  {Eurotium  Aspercjillus  fhirus  of  dc  Banj)  forms  golden 
yellow,  green,  and  brown  growths;  round,  yellow,  olive-green,  or  brown  fruit-heads; 
round,  rarely  oval,  sulphur-yellow  to  l)rown  conidia  with  minute  warts  on  the  surface; 
diameter  5-7  /(.  Aspergillus fumigatus  of  Ercscn  {Asjicrgillus  tiigresrcns  of  Robin)  forms 
green,  bluish,  or  gray  growths;  the  fruit-heads  an>  long,  in  .shape  resembling  an  inverted 
cone;  conitlia.  round,  rarely  oval,  smooth,  mostly  clear  and  colorless;  diameter  'J.o-:i  /(. 
Aspergillus  niger  of  Van  Tieghem  {Eurotium  Aspergillus  tiigrr  ol  de  Jiuri/)  forms  dark 
chocolate-brown  growths;  conidia  are  round,  brownisii-black,  or  grayish-brown  when 
ripe;    surface  smooth  or  warty;    diameter  liAWt  n. 

Aspergillus  can  develop  upon  the  injured  cornea  and  give  rise  to  purulent  inflam- 
matiofi.  Leber  (Graefe's  Arch.,  xxv.)  cultivated  it  upon  the  cornea  and  in  the  anterior 
chamber  of  the  eye  of  the  rabbit.  P'inally,  Aspergillus  also  appears  in  the  pelves  of 
the  kidneys.  Babes  (Biol.  Centralbl.,  ii.)  found  the  conidia  and  hyjjha'  of  a  mouUl  in 
ulcers  of  the  skin  which  were  covered  by  scabs,  and  gave  to  it  tlie  name  of  Uidium 
subtile  cutis. 

Literature. 

(PatJiof/enic  BId.sionn/crtrs. ) 

Acevoli:  Blastomiceti  nei  neoplasmi.     Cbl.  f.  Bakt..  xx.,  bSOG. 

Bernstein:  Pathogenitiit  d.  Blastomyceten.     Z.  f.  klin.  Med.,  40  B<1.,  lOn.'i. 

Binag'hi:  Blastomyceten  in  Epitheliomen.     Zeitschr.  f.  Ilyg..  xxiii..  iMHi. 

Brown:  Coccidioidal  Granuloma.     Jour.  Am.  Med.  Assoc,  1907. 

Buschke:  Die  Hefenmykosen.     Samml.   klin.   Vortr.,  No.  21S,   Leipzig.   1S!)S  (bit.); 

Blastomykose,  Stuttgart,  1902,  u.  A.  f.  Derm.,  ()8  u.  09  Bd.,  1902  (Lit.). 
Busse:  Die  Hefenals  Krankheitserreger, Berlin,  1897  (Lit.);  Pathogene  Hefen.  I'.rgebn. 

d.  allg.  Path.,  v.,  Wiesbaden,  1900  (Lit.),  u.  Handb.  d.  path.  Mikroorg.,  ;.,  190;i 

(Lit.). 
Cohn:  Uober  die  Kleinsche  tierpathog.  Hefe.     C.  f.  B.,  xxxui.,  Orig.,  190.i. 
Corselli  u.  Frisco:  Pathogene  Blastomyceten.     ('bl.  f.  liakt..  xviii.,  1S9.'). 
Curtis:  Saccharomycose  humaine.     Ann.  de  I'ln-st.  Pasteur,  l.S9(>. 
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Assn.,  1903. 
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(Tniula).     Jour,  of  Med.  Pvcs.,  1902. 
Gilchrist  ;in<l  Stokes:  Pseudolupus  Caused  by  a  Blastomyces.     Jour,  of  Kxp.  .MecL, 

iii.,  1S9S. 
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Lowenbach  u.  Oppenheim:   Ilautblastomyko.se.     .\.  f.  Derm..  (19  li<i. 
Maffucci  n.  Sirleo:  Blastomyceten   als  Infect ionserreger.     Zeitschr.  f.    Ilyg.,   xxvu., 

l«tS.  ~  •  .      ,     r 

Neumayer:  Wirk.  versch.  Ilefearten  auf  <1.  thicr.  u.  mensciil.  <  )rgaiiismu.s.     Arcli.f. 

Ilvi:.,  xii.,  1S92. 
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Ophiils:  Coccidioidal  Granuloma.     Jour,  of  Anier.  .Med.  A.ssn.,  190.'). 
Ormsby  and  Miller:  Systemic  Blastomycosi.s.     Jour.  Cut.  Dis..  M.-irch,  190.5. 
Rabinowitsch:  Pathogene  Hefearten.     Zeitschr.  f.  Ilyg.,  x.\i.,  1H9.). 


684  THE   PATHOGENIC    YEASTS    AXD    MOULDS. 

Ricketts:  Oidiomycosis  (Blastomycosis)  of  the  Skin  and  its  Fungi.     Jour,  of  Mod. 

Res.,  1901. 
Roncali:  Blastomyceten  in  Sarkomen.     Cbl.  f.  Bakt.,  xviii.,  189o. 
Sanfelice-  Pathogene  "Wirkung  d.  Blastomyceten.     Cbl.  f.  Bakt.,  xvii.  and    xviii.; 

Zeitschr.  f.  Hvg.,  xxi.,  xxii.,  1896;    xxvi.,  1897;    xxix.,  1898;    xliv.,  1903. 
Sternberg:  Uiiters.  iiber  pathogene  Hefen.     Beitr.  v.  Ziegler,  xxxii.,  1902. 
Weis:  PV)ur  Pathogenic  Torulse  (Blastomycetes).     Jour,  of  Med.  Res.,  1902. 
Wolbach:  The  Life  Cvcle  of  the  Organism  of  "  Dermatitis  Coccidioides."     Jour,  uf 

Med.  Res.,  1904. 

{The  Moulda  and  ihc  Mould- Mi/coses.) 

Baumgarten :  Die  pathogenen  Hyphomyceten.     Deut.  Medicinal-Zeitung,  1884;  Lehr- 

buch  der  path.  Mykologie,  1889;    Jahresbericht. 
Bezold:  Ueber  Otomykosis.     Zur  Aetiologieder  Infectionskrankheiten,  Miinchen,  1881. 
Boyce:  Remarks  upon  a  Case  of  Aspergillus  Pneumonomvcosis.     Jour,  of  Path.,  i., 

1892. 
Busse:  Schimmelpilze.     Ergebn.  d.  allg.  Pathol.,  vii.,  Wiesb.,  1903. 
Ceni:  Gli  Aspergilli  nell'  etiologia  della  Pellagra.     Riv.  Sper.,  xxviii.,  1902;  Lokalisat. 

d.  AspergilLi3.sporen  in  den  Mesenterialdriisen  der  Pellagrakranken.     C.  f.  a.  P., 

xiv.,  1903;  Le  proprieta  tossiche  dell'  Aspergillus  fumigatus.     B.  v.  Ziegler,  xxxv., 

1904. 
Chantemesse:  P.seudotuberkulose,  auf  Pilzwucherungenberuhend.     Cbl.  f.  allg.  Path., 

Dubreuilh:  Les  moisissures  parasitaires  de  Thomme.  Arch,  de  meu.  exp.,  iii.,  1891 
(Lit.). 

Fiirbringer :  Lungenmykose  beim  Menschen.     Virch.  Arch.,  66  Bd.,  1876. 

Grawitz:  Schimmelvegetation  im  thier.  Organismus.     Virch.  Arch.,  81  Bd.,  1880. 

Hochheim:  Pneumonomykosis  aspergillina.     V.  A.,  169  Bd.,   1902. 

Hlickel:  Mucor  corymbifer  (im  iiuss.  Ohr).     Beitr.  v.  Ziegler,  i.,  Jena,  1885. 

Kitt:  Mykose  d.  Luftwege  d.  Tauben.     Deut.  Zeitschr.  f.  Thiermed.,  vii.,  1882. 

Kotliar:  Contrib.  a  I'et.  de  la  pseudotuberculose  aspergillai'e.  Ann.  de  I'lnst.  Pas- 
teur, viii.,  1894. 

Leber:  Grafe's  Arch.,  xxv.;    Die  Entstehung  der  Entziindung,  Leipzig,  1891. 

Lichtheim:  Pathogene  Mucorineen.     Zeitschr.  f.  klin.  Med.,  vii.,  1883. 

Lindt:  Neuer  pathogener  Schimmelpilz  aus  d.  Gehorgang.  Arch.  f.  exp.  Path.,  xxiv., 
1889;  Ueb.  einige  pathogene  Schunmelpilze.  Arch.  f.  exp.  Path.,  xxi.,  ISSti; 
xxv.,  1889. 

Obici:  Pathogene  Eigensch.  d.  Aspergillus  fmuigatus.  Beitr.  v.  Ziegler,  xxiii.,  1898 
(Lit.). 

Oppe:  Schiramelmykose  d.  harten  Hirnhaut.     Cbl.  f.  allg.  Path.,  1897. 

Pearson:  Pneumonomycosis  due  to  the  Aspergillus  fumigatus.  Proo.  of  the  Path.  Soc. 
of  Philadelpliia,  1900. 

Perroncito:  .Mycose  aspergillaire.     Arch.  ital.  de  Biol.,  vii.,  1886. 

Plaut:   llypheiijiilze.     Handb.  d.  pathog.  Mikroorg.,  i.,  Jena,  1903. 

Podack:  Aspergillusmykosen  im  Respirationsapparat.  Virch.  Arch.,  1.39  Bd.,  189.5 
(Lit.). 

Potain:  Un  cas  de  tuberculose  aspergillaire.     L'Union  med.,  1891. 

Pusch:  Fadenpilze  bei  Thierkrankheiten.     Ergebn.  d.  allg.  Path.,  iv..  1899. 

Renon:  Rech.  clin.  et  exp.  sur  la  pseudotuberculose  aspergillaire,  Paris,  1893;  Etude 
sur  I'aspergillose  chez  les  animaux  et  chez  I'homme,  Paris,  1897  (Lit.). 

B-ibbert:  Der  Untergang  pathogener  Schimmelpilze  im  Korper,  Bonn,  1887;  Ueljer 
wiederholte  Infection  mit  pathogenen  Schimmelpilzen.     Deut.  med.  Woch.,  18SS. 

Roeckl:   Ucber  Pneumonomj^kosen.     Deut.  Zeitschr.  f.  Thiermed.,  x.,  1884. 

Both-well:  Experimental  Aspergillus.     Jour,  of  Path.,  vii.,   1900. 

Saxer:   Pneumonomykosis  aspergillina,  Jena,  1900. 

Schenck:  Subcutaneous  Abscess  Caused  by  a  Fungus.     J.  Hopkins  Hosp.  Bull.,  1898. 

Schiitz:  Das  Eindringon  von  Pilzsporen  in  d.  Athmungswege  u.  die  dad.  bedingten 
I'^rkrankungen  d.  lAuige;  Pilz  d.  Iliihngrindes.  Mittheil.  a.  d.  K.  Ges.-Amte,  Ber- 
lin, 1884. 

Siebenmann:  Die  Fadenpilze  Aspergillus  flavus,  niger  u.  fumigatus,  Eurotium  repens, 
u.  .Vspergillus  glaucus,  Wiesbaden,  1883;  Die  Schimmelmykosen  d.  Ohres,  Wies- 
baden, 1889. 


FA  V  ITS. 


(T/irn.s/i.) 


685 


Bohn:  Soor.     Gorlumlfs  Handb.  d.  Kimlerkraiikli.,  iv. 

Cao:  Oidieu  u.  Oidioniykose.     Zoitschr.  f.  HvR..  :U  Bd     I'HK)  (Tit  ") 

Fischer  u.  Brebeck:  Zur  Morpli.    u.   8yst.    d.    Knlun,.ii>c.-.     .Mnnili:;    c.-.mlida   u.   d 

^oorerreger.  Jena,  1S94. 
Grawitz:  Parasit  des  Soors.     Viicli.  Arch..  lOH  Bd  ,  issii 
Heller:  Zur  Lehre  v.  Soor.     Deut.  Arclv.  f."  kliii.  Mod..  TmH.!..  is'.).", 
Heubner:  Soor-Allgemeininfektion.     D.  mod.  WOch.,  iltOli 
V.  Hibler:  Py-imie  mit  Soorinfektion.     Cbl.  f.  Ji..  Uri<'-     .\x.\vi     l'»()l 
Kehrer:  Dor  Soorpilz,  Hoidolhorjj;,  1883.  '^  '  ••     •      ■ 

Linossier  ot  Roux:  Cliainpiirnon  du  muguet.     Arch,  de  mod   o.xp     ISOO 
Plant;  Sy-t.  Stolhing  d.  Suorpilzcs,  Leipzig,  1885;    Neiie  Cnters.  z.  syst'.  Stollung  d. 

.Nd.Mpilzos,  Leipzig,  18S7;    Hyphenpilze.     Ilandh.  d.  patli.  .Mikroorg..  i.,  19();{ 
Kees:  >ooipilz.     Sitzungslicr.  d.  phys.-med.  .Soz.  zu  l^rhiiiiron,   1877.  1878 
Schmidt,  M.  B.:  Die  Locahsatiou  d.  .Soorpilzes  in  den  Luttweiren  li.  .sein  kindringon 

m  (.his  Eindegewebe  der  Oe.sophagusschleimhaut.     Beit.  v.  Zieglcr,  viii     iM'tO 
Schmorl:  Ein  Fall  von  Soormetastase  in  der  Niere.     Cbl.  f.  liakt.,  vii.,  18!»(). 
Soltmann:  Soor.     Eulenburg's  Realeiicvklop.,  xxii..  189i». 
Steiner:  Zur  Pathogenese  d.  Soorpilzes.'    Cbl.  f.  Bakt..  xxi.,  18J»7. 
Teissier:  Champignon  du  muguet.     Arch,  de  mod.  oxj)..  ix     1,S<»7 
Zenker:  Hirnabscess.     Jahresber.  d.  Ces.  f.  Natur- u.  jioMk'.'iu  Dresden.  1861-02. 

.^  l.si>.  Thread=fungi  aic  to  be  iv.uaidcd  as  tlic  exciting  cause  of 
disease  iu  certain  affections  of  the  skin,  as  /(iriis,  herpes  foti.siiraii.s. 
pityriasis  versicolor,  erythrasina.  Jii  all  of  these' diseases  the  epithjdial 
parts  of  the  skin  coutain  colonies  of  liyplite  and  coiiidia,  and  there  re- 
mains no  doubt  that  their  presence  can.ses  in  part  ti.ssue-deiieneralion.s, 
and  in  part  proliferations  and  intiamnuitions. 

The  fungus  of  favus  (Fi^ti.  ."ii:)  is nsnally  called  Achorion  Schonleini 
(discovered  by  Sehonleiu  in  1839). 

Favus  (tinea  favosa,  scald-head)  affects  particnlarly  the  liaiiy  jtortions 
of  the  head,  more  rai-ely  other  regions,  as,  for  example,  tlie  snbstanee  of 
the  nails.  It  is  characterized  by  tlie  fornmtion  of  d\svi>  (favus  scutiiia), 
varying  in  size  from  that  of  a  lentil  to  that  of  a  five-cent  ])iece,  of  a  sul- 
phnr-yellow  color,  and  indented  or  pierced  by  a  liair,  Jn  an  abort i\e 
course  it  may  merely  form  S(!ales  similar  to  those  of  lierpes. 

According  to  Kai)osi,  the  favus  scutnlum  oi-iginates  as  a  small,  punc- 
tiform,  yellow  focus  lying  under  the  ejiiderniis  and  juMiet  rated  l>y  a  haii-. 
This  grows  in  a  few  weeks  to  the  size  of  .i  lentil  and  then  tonns  a  sul- 
phur-yellow, indented  disc  showing  through  the  ni)per  layers  of  tlie 
skin.  The  scutnlum  consists  of  hyplue  aiul  conidia  si)ore.s,  and  lies  iu  a 
cup-shaped  depression  of  the  skin,  beneath  the  horny  layer  which  is 
drawn  away  above  it.  If  the  mass  be  removed  dni-ing  life,  the  cavity 
shows  a  red  moist  surface.  The  favus  itself  forms  a  while,  crumbling 
mass  which  is  easily  disintegrated  in  watei-. 

If  the  scutula  are  not  removed,  they  .join  together  to  form  laiger 
masses.  When  the  epideiniis  is  de.s(piamated  the  fa\  iis-mass  becomes 
exposed  and  dries  up  into  a  yellowish-white,  mortar  like  jnaterial.  Tin- 
hairs  apijear  lustreless,  as  if  covered  with  du.st,  and  are  easily  ]»idled 
out,  since  the  mycelia  and  conidia  of  the  fungus  iKMielrafe  into  the  Jiaii- 
shaft  and  hair-bulb,  as  well  as  into  the  sheath  of  the  hair-root. 

Through  the  gi'owth  of  the  fungus-masses  the  hairs  may  not  only  lu- 
shed, but  the  papilhe  may  become  atro])hic.  At  the  same  linn-  t  la-re  is 
produced  in  the  neighborhood  of  the  liair-follicle  a  mor«'  or  less  inb-ns*- 
inflammation  which  may  take  on  an  ecz(-matous  character. 

The  development  of  achoiion  in  tin-  nails  (oni/fhoiiii/rosiK  faroxa )  gi\es 
rise  to  sulphur-yellow  dei)osits  or  uniform  thickenings  of  theiKirenchyma 
of  the  nails  with  simultaneous  loosening  and  chee.sy  disintegration  of  the 
same. 

Trichophyton  tonsurans,  the  fungus  of  herpes  tonsurans  i"/>arl>cr's 


686  THE    PATHOGENIC    YEASTS    AND    MOULDS. 

itch,"  "ringworm"),  consists  of  long  narrow  threads,  branching  but  little, 
and  with  few  conidia.  It  forms  no  scutnlous  masses,  but  penetrates  easily 
into  the  hair-shaft,  and  makes  the  hairs  brittle.  It  shows  certain  differ- 
ences of  growth,  according  to  whether  the  herpes  develops  u^jon  hairy 
surfaces  or  upon  areas  devoid  of  hairs. 

Herpes  or  Trichophytosis  tonsurans  capillitii  forms  bare  discs  varying  in 
size  from  that  of  a  five-cent  piece  to  that  of  a  dollar.  These  spots  in 
which  the  hairs  are  broken  off  short  look  like  places  in  which  the  hair 
has  been  badly  shaven.  The  surface  is  smooth  or  covered  with  scales, 
and  somewhat  reddened  at  the  border  of  the  disc.  If  the  fungus-threads 
penetrate  into  the  hair-follicles,  pustules  and  scabs  are  formed.  Such 
discs  may  appear  in  many  places,  and  may  constantly  increase  in  size 
until  healing  finally  takes  i)lace. 

On  places  devoid  of  hairs  the  herpes  forms  vesicles  {Herpes  tonsurans 
vesiculosus),  and  red  scaly  spots,  discs,  and  circles  (Herpes  tonsurans  squa- 
mosus).  At  times  red  spots  appear  in  numerous  places;  these  quickly 
spread,  and  as  rapidly  heal.  The  fungus  is  found  between  the  upper- 
most layers  of  the  epidermis,  just  beneath  the  stratum  corneum  (Kaposi). 

If  trichophyton  develops  in  the  nail,  the  nail  becomes  cloudy,  scales 
off,  and  is  easily  broken — a  condition  designated  as  onychomycosis  tricho- 
phytina. 

Sycosis  xmrasitaria  arises  through  the  fact  that  the  development  of  the 
fungus  is  accompanied  by  a  severe  inflammation  of  the  hairy  parts  of 
the  skin,  leading  to  infiltration  and  suppuration — that  is,  to  the  forma- 
tion of  pustules,  abscesses,  and  papillary  proliferations.  According  to 
Kaposi  and  others  eczema  marginatum  is  also  caused  by  the  trichophy- 
ton tonsurans.  The  condition  occurs  in  those  regions  where  two  surfaces 
of  skin  come  into  contact  with  each  other  and  are  macerated  by  sweat; 
and  is  characterized  by  the  formation  of  vesicles,  pustules,  and  scabs, 
which  are  situated  in  the  periphery  of  a  pigmented  surface. 

Microsporon  furfur,  the  fungus  of  pityriasis  or  mycosis  versicolor 
or  dermatomycosis  furfuracea,  occurs  likewise  in  the  form  of  hyphaB 
and  conidia,  which  are  somewhat  smaller  than  those  of  other  skin-fungi. 
The  pathological  changes  produced  by  this  fungus  are  characterized  by 
the  formation  of  pale  yellow  or  yellowish-brown  to  dark-brown  and 
brownish-red  spots,  varying  in  size  from  that  of  a  lentil  to  that  of  the 
hand,  sometimes  smooth  and  shining,  at  other  times  dull  and  exfoliating, 
and  of  irregular  shape.  They  may  be  spread  uniformly  over  large  areas 
of  skin;  and  are  found  chiefly  upon  the  tiunk,  neck,  and  flexor  surfaces 
ol'  Ihe  extremities,  but  never  upon  the  hands,  feet,  or  face. 

Microsporon  minutissium  is  the  name  given  to  a  thread-fungus, 
which  is  found  in  the  skin  afl'ection  known  as  erytlirasma  (von  Baren- 
sprung).  The  disease  is  characterized  by  the  formation,  on  the  inner 
side  of  the  thigh,  of  brown  or  reddish-brown  patches,  Avhich  are  only 
slightly  scaly,  and  may  be  as  large  as  the  palm  of  the  hand.  The  fungus 
is  found  in  the  epidermis,  and  is  smaller  than  that  of  pityriasis. 

The  thread-fungi  occurring  in  the  diseased  areas  of  the  skin  may  be 
cultivated  upon  proper  media  (agar-agar,  agar-gylcerin,  gelatin,  pota- 
toes, blood-serum,  etc.),  and  on  such  the  conidia  develop  into  single  and 
branching  threads,  which  become  jointed  (Fig.  522,  a),  and  form 
chains  of  short  cells  (J)).  Club-like  formations  which  frequently  ap- 
pear upon  the  ends  of  the  threads  in  cultures,  are  regarded  by 
Quincke  and  Elsenberg  as  imperfect  sporangia.  The  botanical  posi- 
tion of  these  fungi  is  not  yet  determined ;  and  nothing  is  known  with 


TKICOPini'ON. 


nsv 


ctMtainty  coiicernini 
bod}'. 


theii  disti'il)u1i< 


MltsilU^  of  111,-  ll 


According  to  Quincke,  three  forms  of  fungi  occur  in  favus-inassos,  two  of  thcso  hcini; 
varieties  of  one  species  of  fungus.  Els^nberg  found  oidy  two,  which  ho  rojrards  as  hoiiig 
varieties  of  the  same  species.     Pick,  Plant,  and  Biro  beheve  firmly  in  the  etiological 

unity  of  favus. 

Sabouraud  advances  the  view  that  the  fungi  causing  trichophytosis  represent  very 
dift'erent  species,  all  of  which  belong  to  the  geinis  Bntritlis.     A'r„,svm/  distinguishes  three 
groups  of  trichophyton-fungi  according  to  the  ditTercnt  appearances  of  the  cultures  on 
]>otato,  ami   emphasizes,  moreover,  the 
ililTerences  in  their  organs  of  generation 
and  fructification.     Rosenbacli,  who  has 
>tudied   the   moidds   occurring    in    deeji 
sui)])urating  inflammations  of  the  skin, 
clitt'crentiates  several  trichophj-ton-fungi 
:i>  the  cause  of  these  affections. 

According  to  Spietschkn,  the  Micro- 
.<)>oron  furfur  may  be  cultivated  from 
the  scales  of  the  skin,  and  in  cultures 
can  be  very  well  differentiated  from  tli' 
other  pathogenic  thread-fungi.  Througl  • 
tlie  inoculation  of  the  fungus  a  tj^Dic:: 
mycosis  may  be  produced  in  man. 

From  the  great  number  of  receni 
investigations  by  various  writers  it  is 
impossible  to  deduce  anything  definite 
concerning  the  number  of  kinds  of  favvi-- 
and  trichophyton-fungi.  It  is,  however, 
evident  from  these  investigations  tha! 
tlie  nature  of  the  nutrient  medium  is  of 
great  influence  on  the  character  of  the 
growth  {Sabouraud,  Waelsch),  and  th? 
tlifference  in  findings  is  to  be  referred  in 
a  great  measure  to  differences  in  the 
nutrient  media  on  which  the  moulds 
were  grown. 

Inoculations  with  fungi  grown  in 
cultures,  into  the  skin  of  human  beings, 
rabbits,  mice,  etc.,  which  were  made  by 

Crawitz,  Boer,  Munnich,  and  others,  gave  partly  negative,  partly  positive  resu'.ts.  Ac- 
cording toPlaut,  the  inoculations  never  give  positive  results  when  spore-formation  ha.s 
already  taken  place  in  the  cultures. 

Von  Hebra  has  described  {Wierier  mcd.  BliiUer,  1881:  "  Die  kraiikh.  Wriind.  d. 
Haut,"  Braunschweig,  1881)  as  dcruKdounic nsis  diffusa  flexor um  a  peculiar  itching  der- 
matosis, which  occurs  on  the  ell)o\v  and  hen  1  of  the  kiiee  and  is  thought  to  be  caused 
by  fungi,  which  are  like  those  of  pityriasis  versicolor. 

According  to  the  investigations  by  TFe/jmer,  the  cause  of  the  skin  eruption  known  aw 
V)kelau.  which  occurs  in  various  South  Sea  Islands  (Fiji,  Samoa,  and  Solomon)  and  wiiich 
is  characterized  by  the  formation  of  scaly  rings,  is  an  Aspergillus. 

Favus  and  herpes  tonsurans  occur  also  in  domestic  animals,  as  well  as  in  mire  and 
rots  (cf.  Friedeberger  and  FrOhner,  "  Lehr.  d.  spec.  I'athoiogie  der  Hausthiere '"). 
Waelsch  inoculated  human  individuals  wnth  favus  fungi,  whicli  he  luui  cultivatetl  from 
mice  affected  with  fi^vus,  and  obtained  tyjiical  favus  scutularis. 

Intravenous  injections  of  favus-fungi  into  rabbits  {Bukorsky)  produced  in  the 
lungs  of  these  animals  a  form  of  pseudotuberculosis;  and  cellular  luxlules  are  found  in 
which  fungus  threads  have  developed  in  a  manner  suggesting  the  lesions  of  actinomy> 
cosis.     After  a  time  the  fungi  die. 

In  invertebrate  animals  there  not  infrequently  occur  diseases  pnxiuced  by  my- 
filium-fungi.  Thus  Balri/tis  Bassiani  causes  the  so-called  ?nusrardin>'  in  silkwonns; 
<'ordi/rcps  mililaris  destroys  the  injurious  pine-s|Mder  (iastropachia  piui;  Tarirhium 
meijaspermum,  a  black-colored  fungus,  killr.  the  destructive  earth-cat«-rpillar  .Ir/roM^ 
segelum.  Fungi  belonging  to  the  genus  Fmpusa  attack  especially  tin-  caterpillars  of  the 
cabbage-butterfly  {Empusa  radicans),  and  the  house-fly  {Empum  musra),  their  inyceliii 
growing  all  through  the  caterpillar  and  finally  killing  it.  Acliyln  vroUferu,  uccnrdnig  to 
Harz  {Jahresber.  d.  Miinchener  Thierarzneischule.  1882-83),  grows  through  the  mus- 
culature of  crayfish,  and  is  the  cause  of  the  crayfish-pest. 


lirancliiii!,'  t 

lll,.,„i„  wall    i.ilii;     1' 

i.iiii>  >>  Ml.  II  ii,i>f  ileli 

rate  walls;  i 

'»,  threads  Willi   tin 

irk-VVallini.    8llnrl  MK- 

ini-nts,  sonic 

of  them  bcinn  split' 

ri.'al.     X  270. 

THE    PATHOGENIC    YEASTS    AND    MOUIiDS. 


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lb.,  xxxi.,  Orig.,  1902. 
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TJnna:   Drei  Favusarten.     Fortschr.  d.  Med.,  x.,  1892. 

Waelsch:  Anatomic  des  Favus.     Arch.  f.  Derm.,  31  Bd.,  1895;    Anatomic  d.  Tricho- 
phytosis,    lb.,  35  Bd.,  1896;    Mannigfaltigkeit  d.  Wachsthums  d.  pathog.  Schim- 

nie'lpilze.     lb.,  37  Bd.,  1896;   Anatomic  d.  Pityriasis  versicolor.     lb.,  38  Bd.,  1897; 

l''avus  bei  Thieren  u.  dessen  Bezich.  z.  Favus  d.  Menschen.     Prag.  med.  Woch., 

I S9S. 
Wehmer:  Dcr  Aspergillus  der  Tokelau.     Cbl.  f.  Bakt.,  Orig.,  xxxv.,  1904. 


CHAPTER  XII. 

The  Animal  Parasites  and  the  Diseases  Produced  by 

Them. 

I.  Protozoa. 


S  183.  Of  the  Protozoa  oc( 


ij;  as  parasites  in  man,  only  a  small 


cysted  amoebiB 


number  was  known  up  to  a  few  years  ago;  and  even  the  known  forms 
but  slight  siguiticanee,  sinee  there  eonld  be  ascribed  to  them 
no  marked  intlncnee  ujtoii  tlic  tissnes. 
Through  the  investigations  of  the  last  few 
years,  however,  dittVrent  forms  have  been 
recognized  as  the  cause  of  morbid  proc- 
esses; and  it  is  quite  possible  that  there 
are  still  other  jjrotozoa  ca])able  of  exciting 
pathological  changes  in  tlie  hnman  body. 
The  foiins  alieaily  lecognized  are  repre- 
sentatives of  all  foni'  classes  of  jnotozoa. 

Of  the  Rhizopoda  liicrc  (»ccnr  in  the  in- 
testine three  amo'bie,  known  as  the  Auki/xi 
Villi  vulgaris,  the  Amoeba  coli  viifis,  and  the  Amaha  di/umteria'.  'llw 
Amoeba  dysenterise  is  certainly  distingnishable  from  the  other  two,  while 
the  Amoeba  coli  vulgaris  and  the  Amoeba  coli  niitis  resemble  each  other 
very  closely,  and  may  possibly  be  identical. 

The  Amoeba  coli  vulgaris  is  a  harmless  intestinal  ]>arasile  which  is 
not  infreciuently  present  in  the  intestine  (Iioos,  Kinse,  J'ascpiale).  The 
Amoeba  coli  mitis  was  observed  by  Roos  and  (Quincke  in  cases  of  chronic 
enteritis  in  patients  who  had  always  lived  in  >»'orth  ( Jermany. 

The  Amoeba  coli  mitis  consists,  according  to  Koos,  of  a  protoplasmic 
cell-body,  from  28-30 //  in  diameter  (in  the  spherical  condition).  It  ex- 
hibits slow  movements,  and  very  freqnently  encloses  foreign  bodies,  foi- 
exami)le,  bacteria  and  food-remains  (Fig.  523,  a).  Besides  the  motile 
form,  there  occur,  according  to  Koos,  also  encysted,  sj)herical  foinis 
which  are  surrounded  by  a  double-contonred  membiane,  and  enclos«' 
clear,  round  vesicles  in  their  interior  (^>).  "When  lid  to  animals  (»-ats) 
no  pathogenic  properties  are  disclosed. 

The  Amoeba  dysenteriae  (identical  with  the  Amoeba  coli  described  by 
Loesch)  has  a  diametei-,  according  to  lioos,  of  f lom  10-25,",  bnt  acconl- 
ing  to  Krnse  and  Pas(piale,  from  10-50".  In  the  cell  body  llieie  ma> 
be  recognized  a  homogen<'ons  ectoi)lasm  and  a\ariable  grannlar  enio 
plasm,  the  arrangement  of  which  vaiies  according  to  the  lorm  <»f  the 
animal  (Fig.  524,  a).  By  staining,  a  nnclens  may  be  made  visible  within 
the  cell.  The  cells  are  ca])able  of  active  movement,  and  assnme  thereby 
the  most  varied  shapes  (d).  They  \'ery  often  contain  foreign  bodies, 
particnlarly  red  blood-cells  or  remains  of  snch  (6),  or  are  studded  with 
44  Gs'j 


690 


THE   ANIMAL   PARASITES. 


Fig.  bH.—Amaeba  dysenteriw  sive  Amccha  coli  felis. 
(After  Roos.)  a,  Amoebae  without  inclusions:  h,  amoebsB 
containing  blood ;  c.  amcebse  wllb  large  vacuoles  in  their 
protoplasm  ;  d,  young  forms ;  c,  encysted  forms.    X  665. 


clear  vacuoles  (c).     According  to    Eoos,   they  may  also    become   en- 
cysted (e). 

According  to  investigations  by  Koch,  Kartulis,  Kruse,  and  Pasquale, 
they  are  invariably  present  in  the  dysentery  prevailing  in  Egypt,  and 
are  usually  also  demonstrable 
in  the  dejecta.  They  have 
also  been  observed  in  cases  of 
dysentery  in  Eussia  (Loesch, 
Massiutin),  in  America  (Os- 
ier, Councilman,  Lafleur,  Lutz, 
Dock),  in  Germany  (Eoos), 
and  in  Austria  ( Ko vacs) .  Ac- 
cording to  investigations  by 
Kartulis,  Councilman,  La- 
fleur, Kovacs,  Eoos,  Kruse, 
Pasquale,  and  others,  it  can- 
not be  doubted  that  they  are 
of  some  significance  in  the 
origin  of  certain  forms  of  dysentery.  It  is  only  questionable  whether 
they  alone,  or  only  with  the  aid  of  changes  produced  by  bacteria,  are 
able  to  bring  about  pathological  changes.  In  support  of  the  latter 
theory  is  the  fact  that,  when  present  in  the  tissues,  they  are  always  ac- 
companied by  bacteria. 

Amoebic  dysentery  is  characterized  by  the  occurrence  of  a  hsemor- 
rhagic  catarrh,  and  by  the  formation  of  circumscribed  ulcers  with  under- 
mined edges.  The  amoeba)  increase  not  only  in  the  intestinal  mucosa, 
but  also  penetrate  into  the  mucosa  and  submucosa,  and  there  form  large 
colonies,  in  the  region  of  which  the  tissue  undergoes  necrosis  without  tlie 
formation  of  any  large  amount  of  exudate.  By  the  rupture  of  the  sub- 
mucosal foci  through  the  mucosa  there  are  formed  ulcers  with  under- 
mined edges,  which,  gradually  increasing  in  size,  may  attain  large  di- 
mensions. 

If  abscesses  of  the  liver  arise  during  the  course  of  an  amoebic  dysentery, 
these  may  also  contain  the  amoebie  in  addition  to  bacteria;  and  it  may 
be  assumed  that  the  former  also  take  part  in  the  destruction  of  the  liver 
tissue. 

The  amcehce  of  dysentery  are  ixdhogenic  for  cats,  and,  when  fed  to  them 
or  when  introduced  into  the  rectum  of  the  animal,  cause  a  rapidly  pro- 
gressive, often  fatal  dysentery,  which  is  similar  in  all  respects  to  amoebic 
dysentery  in  man.  The  amoebae  also  iDcnetrate  into  the  mucosa  and  sub- 
mucosa of  these  animals. 

Von  Leyden  and  Schaudinn  ("  Leydenia  gemmipara,"  Sitzber.  d.  K.  Akad.  d.  Wiss., 
Berlin,  1896)  found,  in  the  fluid  of  two  cases  of  ascites  occurring  in  malignant  disease  of 
the  abdomen,  an  amoeba  which  consisted  of  colorless  gelatinous  cells,  which  put  out 
pscudopodia,  and  showed  a  hyaline  entoplasm  and  a  granular  ectoplasm.  They  were 
found  chiefly  lying  together  in  groups. 


Literature. 

{Amwba'.) 

V.  Baumgarten:  Jahresbericht,  xvii.,  Leipzig,  1903. 

Behla:  Die  Ainoben,  Berlin,  189S  (Lit.). 

Celli  u.  Fiocca:  Beitr.  z.  Amobenforschung.     Cbl.  f.  Bakt.,  xvi.,  1894. 


FLAGKLLATA. 


691 


Councilman  and  Lafleur:   Amcrbic   Dvsomorv.     Johns    TToi^kins    IIosi).     R.-m      ii 

Baltimore.  1891.  '  '  ■  .    ■      •, 

Cramer:  Aniobendy.senterie.     Cbl.  f.  allj:.  I'atli.,  vii.,  IS'.Ml  (Lit.). 
Dock:  .\moeba  coli  in  Dysentery.     Daniel's  Texas  .Med.  Joiirn.,  IS'.H). 
Doflein:   Die  Protozoen  als  Parasiten  und  KrankheitseiTe.s^er.     Jena,   I'.IOl    (Lit.). 
Doria:  Protozoen  bei  der  Endometritis  chron.  jilandularis.     .\rch.  f.  Cyn..  17  Hd.,  ls<.M. 
Epstein:  Monocercomonas   horn.   u.   Amoei)a  coli   bei   Kin(lerdiarrh<ieii.      I'ri>'    med 

Woch..  1893. 
Feinberg:   Unterscheid.  v.  Amiiben  n.  Kru-perzellen.      I^'ortsehr.  d.  .Med.,    IS'.IU;    l{otiia- 

nowskisehe  Fiirbung.     Berl.  klin.  Woch.,  WHYA. 
Gilchrist:   Protozoan  Infection.     Johns  Hopkins  Ilosj).    Rv\>..   189(). 
Harris:  .Vnucbic  Dysentery.     Am.  Journ.  of  the  Med.  Sc.,  1898. 
Janowski:  .Vetiologie  d.  Dysenterie.     Cbl.  f.  Bakt.,  xxi..  1897. 
Kartulis:  Zur  Aetiologie  der  Leberabscesse.     Cbl.  f.  Bakt.,  ii.,  1887;    Pathogeiie.se  der 

Dvsenterieamoben.     lb.,  ix.,  1891;    Pathogene  Protozoen.     Zeitschr.  f.  Hyg.,  xiii., 

1893. 
Kovacs:  Beobacht.  iib.  Amobendysenterie.     Zeitschr.  f.  Hyg.,  xiii.,  189"_'. 
Kruse  u.  Pasquale:  I'nters.  iib.  Dysenterie  u.  Leberabscess.     Zeitschr.  f.  Hyg..  xvi., 

1894. 
Losch:  Massenhafte  Ent vvickelung  von  Amoben  im  Dickdarm.     ^■ireh.  Arch.,  (i.')  Bd., 

1875. 
Lowit:  Die  Leukamie  als  Protozoeninfection,  Wiesbaden,   1900;    Specif.  Farbnng  d. 

Hiiniamiiba  Ieuc;emia>  magna.     Beitr.  v.  Ziegler,  xxviii.,  1900;    Weitere  Beobach- 

tungen  iiber  die  Parasiten  der  Leukamie.     Zeitschr.  f.  Heilk..  xxi.,  1900. 
Lutz:  Zur  Kenntniss  der  Amobenenteritis.     Cbl.  f.  Bakt.,  x.,  1891. 
Massiutin:  Ueber  die  Amoben  als  Parasiten  des  Dickdarms.     Cbl.  f.  Bakt.,  vi.,  1889. 
Osier:  L'eber  die  l)ei  Dysenterie  vorliandeiie  Amobe.     Cbl.  f.  Bakt.,  vii.,  1890. 
Pfeiffer:  Die  Protozoen  als  Krankheitserreger,  Jena,  1895. 
Posner:  Amoben  im  Harn.     Berl.  klin.  Woch.,  1893. 
Quincke:  Protozoenenteritis.     Berl.  klin.  Woch.,  1899. 
Quincke  u.  Rocs:  Amobenenteritis.     Berl.  klin.  Woch.,  1893. 
Rocs:  Zur.  Kenntn.  d.  Amobenenteritis.     Arch.  f.  exp.  Path.,  xxxiii.,  1894. 
Schneidemiihl:  Die  Protozoen  als  Krankheitserreger,  Leipzig,  1898. 
Schuberg':  Die  parasitischen  Amoben  des  menschl.  Darms.     Cbl.  f.  Bakt.,  xiii.,  1893 

(Lit.). 
Tajardo:  Amobenenteritis  und  Hepatitis.     Cbl.  f.  Bakt.,  xix.,  189G. 
Tenoglia:  Entero-colite  par amoeoa coli.     .\rch.  ital.  de  Biol.,  xiv.,  1890. 
Turk:  Ueber  die  Hamamoben  Lowit's.     Verb.  d.  Congr.  f.  inn.  Med.,  Wiesl)aden,  1900. 
Walker:  The  Parasitic  Amoebae  of  the  Intestinal  Tract  of  Man  and  Other  .Viiimals. 

Jour,  of  Med.  Res.,  1908. 
Wesener:  I'nsere  gegenw.  Kenntn.  iiber  Dysenteric,     ('i)l.  f.  .dig.  Path.,  iii.,  189'J. 

§  184.   A  large  number  of  specie.s  of  the  Flagellates  (.siil)-('his.s  of  \ho. 
Mastigophorci)  occur  in  man,   mammals,   and  birds,    iimst    fre([iu'iilly  as 


Fig.  ^t^i.—Ccriotnonax  ititenti- 
naiis.    (After  Davidne.) 


fi.  r>26. — Trichomnnns  hominis, 
after  (Jrassi  (from  Dolli-iri  i. 


Fkj.    ."i27.       'Yrichomona* 

vii(iin<ili.i  (fniin  Dolliin;. 


parasites  of  the  body-passages  accessible  frnm    williutit,   l>iit    ncciirnng 
also  in  tlie  Idood. 

Cercomonas,  Diijai'diii,  a  small    llag(dlat<'  (Fig.  .VJ.lj  willi  a  Ihtgcntim 


692 


THE    ANIMAL    PARASITES. 


on  the  anterior  end  and  a  long-drawn-out  posterior  extremity,  was  ob- 
served by  Kannenberg  and  Streng  in  gangrenous  foci  of  the  lung. 

Trichomonas,  Davaine,  Braun   (Cercomonas  mtestinalis,  Lambl ;  Tri- 
cliomonaa  iiifcstiuali.s,  Leuckart;  Monocercomonas  hominis,  Grassi)  is  a  pear- 
shaped  flagellate,  4-10  p.  long,  with  three  flagella 
on  the  anterior  end  (Fig.  526). 

Trichomonas  hominis  occurs  in  the  small  in- 
testine of  man,  and  has  been  observed  particularly 
in  pathological  conditions  of  the  intestinal  tract 
(typhoid  fever,  cholera,  intestinal  catarrh,  cancer 
of  the  stomach).  It  appears  to  be  a  harmless  in- 
habitant of  alkaline  intestinal  contents. 

Trichomonas  vaginalis,  Donne,  is  a  flagellate 
very  similar  to  the  Trichomonas  hoiniiiis  (Fig.  527), 
and  is  often  found  in  the  human  vagina.  Accord- 
ing to  Miura,  Marchand,  and  Dock,  it  inay  occur 
in  the  human  urinary  bladder. 

Lamblia  intestinalis  {Megastoma  euiericum, 
Grassi;  Mrr/a.^toma  iHtcstiiialis,  Blanchard;  Ccrco- 
monas  iiite.stitKdi.s,  Lambl ;  Hexamitus  duodenaUs, 
Davaine)  is  a  turnip-shaped  animal,  having  an  in- 
dentation on  the  ventral  surface  (Fig.  528,  A,  B). 
It  is  about  10-16  //.  long,  and  is  found  especially  in  the  upper  part  of 
the  small  intestine,  and  has  been  observed  in  man,  mice,  dogs,  cats, 
sheep,  and  rabbits.  The  parasite  clings  tightly  to  the  epithelium  of  the 
intestine,  but  no  j^athological  changes  can  be  demonstrated  in  the  un- 
derlying tissue. 


Fig.  528. — Lamblia  in- 
testinalis (after  Grassi  and 
Schewiakoft").  A,  View 
from  ventral  surface;  B, 
view  from  the  left  side. 


Literature. 


(F/ai/Hhdrx.) 


V.  Baumgarten:  Jahresbericht,  xvii.,  Leipzig,  1903. 

Braun:  Die  tieri^^chen  Parasiten  der  Menschen,  Wiirzburg,  1903. 

Dock:  Trichomonas  as  a  Parasite  of  Man.     Am.  Journ.  of  Med.  Sc,  1S9G  (Lit.). 

Doflein:  Die  Protozoen  als  Parasiten  u.  Krankheitserreger,  Jena,  1901. 

Doflein  and  Prowazek:  Die  path.  Protozoen.     Handb.  d.  pathog.  Mikroorg.,  i.,  1903. 

Grassi:  Profist(>s  endoparasites.     A.  ital.  de  Biol.,  ii.  u.  iii.,  1882-83. 

Grassi  and  SchewiakofF.  Megastoma  entericmn.     Z.  f.  wiss.  Zool.,  xlvi.,  1888. 

Hausmann:    Die   I'anisiten  der  weiblichen  Genitalien,  Berlin,  1890. 

Janowski:  Flagellaten  in  den  Faeces.     Z.  f.  klin.  Med.,  31  Bd.,  1896. 

KoUiker  and  Scanzoni:  Trichomonas.     Scanzonis  Beitr.  z.  Geburtsk.,  1855. 

Lambl:  Cercomona.s  et  Echinococcus  in  hepate.     Russ.  med.  Bericht,  1874. 

Lindner:  CiHaten  in  Kopfhautekzem.     Mon.  f.  prakt.  Dermat.,  xvi.,  1893. 

Marchand:  Trichomonas  intest.    V.  A.,  64  Bd.;   Trichomonas  im  Harn.     C.  f.  B.,  xv., 

1894. 
May:  Cercomonas  coli  hominis.     D.  Arch.  f.  kUn.  Med.,  49  Bd.,  1892. 
Metzner:  Megastoma  entericum.     Z.  f.  wiss.  Zool.,  Ixx.,  1901. 
Miura:  Trichomonas  vaginalis  im  XIrin  eines  Mannes.     Cbl.  f.  Bakt.,  xvi.,  1894. 
Moritz  and  Holzl:  Megastoma  entericum.     Miinch.  med.  Woch.,  1892. 
Perroncito:   U(>ber  die  Einkapselung  des  Megastoma  intest.     Cbl.   f.  Bakt..  ii.,    1887. 
Boos:   Uelier   Infusoriendiarrhoe    (Megastoma    entericum,    Trichomonas    intestinaUs, 

("crcomonas  hoiuinis,  Cercomonas  coli  u.  a.).     D.  Arch.  f.  khn.  Med.,  50  Bd.,  1893. 
Bosenberg:  Beflentung  der  Flagellaten  in  Magen  u.  Darm.     D.  med.  Woch.,  1904. 
Schmidt:  Trichomonas  im  Auswurf.     Miinch.  med.  Woch.,  1896. 
Sievers:  Balantidium  coli  und  Megastoma  entericum.     Z.  f.  klin.  Med.,  30  Bd.,  1896, 

".  A.  f.  Verdauungskrankh.,  v.,  1900. 
Streng:  Infusorien  im  Sptitum  bei  Lungengangriin.     Fortschr.  d.  Med.,  x.,  1892. 
Zenker:  Cercomonas  intestinalis.     D.  Zeit.schr.  f.  i)rakt.  Med.,   1879. 


FLACJKM.A'I'A. 


noa 


§  185.  Of  the  Flagellates  thai  (•(•cur  as  blood-parasites  of  man  Uio 
form  known  as  Spirochiete  obermeieri  ((liscoxcu-d  hy  Olu-inicicr  in 
187:))  has  been  known  for  sonu'  time,  hnt  fonnerly  lias  l»een  ehissed  with 
the  spiral  varieties  of  haeteiia  (spirilhi).  The  investigations  of  Schan- 
dinii,  however,  make  it  appear  veiy  probabh^  that  the  spiroeha'tes  arc  to 
be  added  to  the  protozoa. 

Sch<ni(lint}'!i^  conclusions  are  not  iiniversnlly  accepted.  Accordinf;  to  Ann/,  Spi- 
rillum obermeieri  belongs  to  the  bacteria  and  not  to  the  protozoa,  aniflie  l>eliev('>^  that 
the  majority,  if  not  all,  of  the  spirocluetes  will  be  returned  to  their  former  place  anion;: 
the  bacteria.  Sp.  diittoni  andSp.  (jallinanun  have  both  been  shown  to  be  non-jjroto/.o.'d 
in  nature. 


(V\iX.   020)  is  found  constantly  in  tin- 
relapsing  fever  dnrintithe  at'tacks  (d" 
I  of  these  oi'iianisius  in   tin-  Ix.dv    is   the 


i  niiincinns  spiral  t  nnis. 
tion.     Carter  and   J\o»h 


The  Spirochaite  obermeieri 

blood  of  i)atieids  snlferinii-  from 
the  fe\er,  and  the  mnltiplieatio 
cause  of  the  disease. 

The  spiroeluete  is  16-40  ,".  long,  and  ])ossess( 
In  a  fresh,  drop  of  blood  it  shows  very  aeti\e  m 
succeeded  in  producing  the  disease  in  apes 
by  inoculation  with  the  spirocluete.  The 
subcutaneous  inocidation  into  apes  of  blood 
containing  the  spirocha:de  is  followed  after 
several  days  by  an  attack  of  fever,  and  the 
spirochjete  is  fonnd  in  the  blood  dnrir.g  the 
febrile  stage.  The  life  history  of  the  Si)iro- 
chfete  obermeieri  is  not  known,  but  it  tnay 
be  similar  to  that  of  the  spirocluetes  occur- 
ring in  the  blood  of  birds  as  studied  by 
Schaudinn  (see  below).  According  to  the 
autopsy-findings  observed  in  man,  the  S])leen 
is  swollen  and  contains  numerous  yellow 
foci  of  degeneration,  and  often  also  ana-mic  infarcts. 

According  to  investigations  by  Xik  if  orotf,  the  histological  examination 
of  the  spleen  shows  extensive  cell-necrosis  and  cell-degeneration  (Fig. 
530,  c),  as  well  as  deposits  of  fibrin  in  the  veins  of  the  pidp,  and  prolif- 
erative processes  in  the  pulp-cells.  Further,  numerous  large  puli 
(/)  enclose  red  and  white  blood-cells  or  tl 


Fig.  .'>'?0.  S;<in.('irf7.  Ohrnnciiii 
from  tlie  bloud  of  an  nuliviaual  ill 
witli  relapsing  fever.  After  a  dried 
prepuration  stained  with  methylene 
l.liic.      •:  47-.. 


\iO     Po,  non  of  tissue  and  isolated  ( .  IK  from  a  si.leni.  follicle  with  pni  ia  i'<    r.-sis  '"  [<  '  ''^'",f 

\tts  \Mtli  siMiilla;  r,non-Mii(le.it.d  hmphorvtes.    r/.largp.  e.  small   \":Z'T.}.y^^^ 

1 J I .„.!  .-.  ,1  »>i,^,wi_/.  IK  ..iwl  the  rrciniiins:  (/.  free  red  I)I(m><1-<  el.s.     >.  ulmllt  i«<«i. 


Fif, 

fever  I 
lymplKu ' 
phago(  jt(s(  n(  iDsin^ 


■  and  n  d  blood-tt  lis  and  their  remains  ;  (/,  free  red 


694  THE    ANIMAL    PARASITES. 

numerous  ^j^irilla  are  found,  especially  in  regions  which  are  not  -wholly  ■ 

necrosed  but  coutaiu  degenerated  and  necrotic  cells,  in  jjart  free  («),  and  i 

in  part  enclosed  in  leucocytes  (b),  i^artly  well-preserved,  and  partly  be-  1 

ginning  to  show  disintegration.  ^ 

According  to  Karlinski  and  Schaudinn,   the  infection    is    probably  jl 

transmitted  by  bed-bugs.  I 

Spirochietes  have  been  observed  also  in  birds,  owls  (Schaudinn),  geese  'j 

{Sacharoff,  Gabritschewsky),  and  fowls  (Marchaux,  Salimbeni,  Levaditi),  i 

and  may  cause  epidemics  in  which  great  numbers  of  animals  perish.  I 

The  life-history  of  the  Spirochaetes  classed  with  the  bacteria  was  not  known  ]■ 

until  recently.     Through  the  investigations  of  Laveran  and  Schaudinn  it  was  for  the  first  • 

time  determined  that  in  their  life-cycle  there  occurs  an  alternation  of  generation  and  of  I" 

host.     Schaudinn  carried  out  his  studies  on   the   spirochtetes  found  in  the  small  owl  ' 

(Athene  noctua) ,  which  he  named  Spirochceta  ziema  n  ni  (called  by  La  reran  the  Hcemamoeba  '. 

ziemanni).     As  a  result  of  his  investigations  he  believed  that  he  had  demonstrated  the  \v 

transmission  of  this  spirochcete  from  the  owl  into  the  mosquito,  Culex  pipiens,  in  the  [j: 

intestine  of  which  it  passed  certain  stages  of  development,  as  described  in  the  following  '^ 

paragraphs.  h 

Within  the  owl  there  develop  male  and  female  individuals,  the  microgametocytes  ft 

and  the  macrogametes.     Copulation  takes  place  in  the  intestine  of  the  mosquito.     From  |f. 

the  fertilized  macrogamete  there  develops  an  ookinete  which  produces  in  the  intestine  > 

of  the  mosquito  an  enormous  number  of  trypanosome-like  offspring.     These  become  ' 

transformed  into  true  spirochaetes,  spread  throughout  the  body  of  the  mosquito,  increase  ' 

by  longitudinal  division,  and  wander  into  the  cesophagus,  whence,  in  the  act  of  biting,  .' 

they  again  pass  into  the  blood  of  the  owl.     After  an  asexual  period  of  multiplication  in  ; 

the  form  of  spirochaetes  they  again  form  gametes  or  sexual  individuals  in  the  blood  of  :. 

the  owl.     As  the  result  of  their  distribution  throughout  the  body  of  the  mosquito  the  |i 

spirochaetes  may  pass  into  the  ovaries  of  the  latter  and  thereby  be  transmitted  to  the  fv 

next  generation.  I 

The  fertilization  in  the  intestine  of  the  mosquito  follows  a  ripening  of  the  macro-  • 
gametes   (female  cells)   and  the  formation  of  microgametes   (spermatozoa)   from  the 

microgametocytes.     The  ookinete  resulting  from  the  fertilization  of  a  macrogamete  is  i 

a  worm-like  body  rolled  up  into  a  complicated  skein.     Through  the  grouping  of  the  | 

protoplasmic  masses  around  the  individual  nuclei  there  are  formed  small  trypanosome-  j 

like  individuals  having  a  characteristic  fiagellum-apparatus.     Further,  there  may  be  : 

developed  both  male  and  female  individuals.     The  female  forms  are  larger  than  the  ' 

indifferent  forms,  their  plasma  is  dark,  the  nucleus  and  blepharoplast  relatively  small,  ! 

and  the  margin  of  the  imdulating  membrane  is  not  continued  to  form  a  flagellum.     The  j 

males  are  very  small  and  scarcely  recognizable.  j 

Through  continued  division  the  indifferent  spirochaetes  in  the   intestine  of  the  i 

mosquito  also  become  very  small,  so  that  single  individuals  can  barely  be  made  out.  j 

Within  the  blood  of  the  owl  the  spirochaetes  become  parasites  of  the  liaemoglobin-  I 

containing  erythroblasts,  in  that  they  attach  themselves  to  these  by  their  posterior  I 

extremities.     This  is  seen  particularly  in  the  bone-marrow  and  also  in  the  spleen.     After  j 

a  certain  time  they  form  in  the  blood  macrog;jmetes  and  microgametes,  which,  on  gaining  ] 

entrance  into  the  mosquito,  again  form  new  generations  in  the  manner  described.     The  ! 

macrogametes  can  also  produce  new  generations  in  the  blood  without  fertilization  (par-  | 

thenogenesis)  and  thereby  cause  relapses.  | 

The  above-given  life-cycle  of  the  spirochaetes  according  to  Schaudinn  falls  to  the  * 

ground  in  tlio  light  of  Novy's  studies.     The  latter  has  shown  that  the  Spirocha:te  ziemanni  I 

is  not  a  spirochaete,  but  a  tr^^ianosome,  and  has  no  connection  with  the  intracellular  ! 

Earasites  of  the  owl's  blood.     Further,  Xory  regards  Sp.  obcrmeieri  as  belonging  to  the  j 

acteria,  basing  his  view  upon  his  inability  to  demonstrate  in  the  organism  a  nucleus,  ; 

blepharoplast,  undulating  membrane,  or  flagellum  of  the  protozoan  type.     On  the  other  I 

hand  the  spirilla  of  relapsing  fever  possess  whips  having  all  the  characteristics  of  those  j 

of  bacteria,  divide  transversely,  multiply  rapidly,  resist  changes  in  osmotic  tension,  | 

show  a  greater  resistance  to  heat  than  do  the  trypanosomes,  excite  the  production  of  i 
immune  and  germicidal  bodies,  and  do  not  exhibit  the  aerotropism  shown  by  trypan- 
osomes. 

In  relapsing  fever  we  have  most  probably  to  deal  with  a  group  of  closely  related  orga?}- 
isms  {Novy),  which,  while  they  may  in  one  sense  be  regarded  as  distinct  species,  are 
derived  from  one  stem.  Five  distinct  strains  of  spirilla  causing  relapsing  fever  have 
been  discovered:  Spir.  obermeieri.  Spir.  noryi,  Spir.  l-ochi.  Spir.  duttoni.  andSpir.  cartcri. 
These  differ  from  each  other  in  the  duration  and  severity  of  the  initial  attack,  the  fre- 


FLAGELLATA.  695 

quency  and  intensity  of  relapses,  and  in  (lio  niortalitv  fi)llo\viii<;  an  injection  of  a  \niiform 
dose  of  0.25  c.c.  of  spirillar  blood.  The  relapse  is  pi()l)al>lv  due  to  tlie  survival  of  :i  few- 
individuals  that  are  more  or  less  inmuuie.  so  that  a  seruiu-'fast  strain  develops.  This  in 
turn  calls  out  a  new  antibody.  If  this  is  leso  active  or  more  unstable,  or  more  readily 
eliminated,  the  relapses  will  continue. 

If  Schaudititi's  views  on  the  protozoan  nature  of  the  organism  found  in  syi)hiii.s 
{Spir.  pallida,  Treponema  palliilum.)  are  correct,  that  organism  should  then  be  cla.ssed 
here  with  the  protozoa.  At  the  present  time  this  question  cannot  l)e  regarded  as  .settled, 
but  it  is  most  probable  that  the  organism  is  of  l)acterial  nature  and  shoulii  be  cla.ssed, 
along  with  tlie  spirocha^tes  of  relapsing  fever,  witii  the  spiral  forms  of  bacteria  (spirilla). 
(See  Syphilis.) 

Literature. 

{S2)irocli(rlcN. ) 

Cantacuzina:  Spirilloses  des  oies.     Aim.  de  I'lnst.  Pasteur,  1899. 
Gabritschewsky:   Zur  Pathol,  d.  Spirochaeteninfection.     Cbl.  f.  Bakt.,  xxvi.,  lS99,u. 

xxvii.,  I'JOO. 
Heydenreich.:  Der  Parasit  des  Riickfalltyphns,  Berlin,  1877. 
Honl:  Fehris  recurrens.     Ergebn.  d.  allg.'Path.,  iii.,  1897. 
Karlinski:  Aetiol.  des  Gefliigeltyphus.     Cbl.  f.  Bakt.,  Orig.,  xxxi.,  lOO'J. 
Levaditi:  Spirillose  des  ponies.     Ann.  de  ITnst.  Pasteur,  1904. 
Lubimoff:  Patholog.-anat.  Veranderungen  bei  Typhns  biliosus.  \ireh.  Arch.,  98  Bd., 

1.SS4. 
Marchoux  et  Salimbeni:  Spirillose  des  ponies.     Ann.  de  I'lnst.  Pasteur,  UKV.i. 
Metsclinikoif:  I'eb.  den  Phagocytenkampf  bei  Riickfalltyphns.     \'irch.  Arcli.,    109 

Bd.,  1SS7. 
Nikiforoff:  Zur  path.  Anat.  n.  Histol.  d.  iMilz  bei  Recurrens.     Bcitr.  v.  Ziegler,  xii., 

1892. 
Novy:  Studies  on  Spirillum  Obermeieri  and  Related  Organisms.     Jour,  of  Infect.  Dis., 

I<t0(). 
Obermeier:  Cbl.  f.  d.  med.  Wiss.,  1873;    Berl.  klin.  Woch.,  1873,  No.  33. 
Ponfick:  Anat.  Studien  iiber  den  Typhus  recurrens.     Virch.  Arch.,  GO  Bil.,  1874. 
Puschkareff:  Zur  pathol.  Anat omie  der  Febris  recurrens.     Virch.  Arch.,  118  Bd.,  1888. 
Schaudinn:  Generations-  u.  Wirtsweclisel  Inn  Trypanosomen   u.  Spirochaten,  Berlin, 

1004. 
Sudakewitsch:  Rech.  sur  la  fievre  recurrentc.     .Vnn.  de  ITnst.  Pasteur,  v.,  1891. 
"WladimirofF:  Riickfallfieber.     Haiidb.  d.  })ath()g.  Mikroorg.,  ill..  J<-na.  190:i  (Lit.^. 

§  186.  The  genus  Trypanosoma  fonns  ;t  socoiid  class  of  blood-para- 
sites belougiug  to  the  Flagellata,  found  in  man,  nianmials,  and  itirds, 
and  also  in  cold-blooded  animals.  Most  antliois  placid  all  llic  i>aiasitcs 
of  this  class  in  the  genns  tiNpanosoma  and  distinguisii  ditVcrcnl  six'cics. 
Dofiein  di^  ides  them  accorcling  to  tlie  cliarachM'  of  llie  llagclla  inin  three 
sub-genera:  Trypanosoma^  Ti!i})anoinonas,\\\\i\  Jlcrjxtosonia.  \'(tn  W'a.sjc- 
lewski  classes  only  the  blood-parasites  of  the  frogs  and  lish  uifli  Mm-  ti  \  - 
panosomes,  and  would  apply  the  name  Jfrrpctomouas,  given  1)\  Kent, 
to  the  trypanosomes  found  in  mammals. 

Trypanosoma  lewisi,  Kent  (nrrpclonioiias,  TrmxinoiniHKis,  'J'rir/inuin- 
nas,  Jfcvmafomonas)  is  a  very  common  i)arasilc  of  lals.  It  is  S  ;;(»  ,"  long 
and  3-8 /^  broad  (Fig.  531),  consists  <d"  a  iinclcatcd  grannlar  cnlopla.sm 
and  a  delicate  hyaline  ectoplasm  or  ])eriplast('m,  the  latter  forming  an 
undulating  membrane  (Fig.  532,  r)  and  a  llagcllnm  (J)  which  arises  in 
•  the  beak-like  posterior  end  from  a  rod-like  body  and  extends  anteriorly 
along  the  edge  of  the  undtdating  meml)rane. 

The  rod-shaped  body  (/>)  is  designated  micronucleus  ( I'.iadford  and 
Plimmer),  or  nucleolus  (Kabinowitsch  and  Kempner),  or  centro.some 
(Laveran  and  Mesnil),  or  blepharo])last  (Von  Wasielew.ski,  8enn,  Schau- 
dinn). It  has  the  significance  of  a  nucleus  and  arises  from  the  chief 
nucleus  (Schaudinn). 


696 


THE   ANIMAL    PARASITES. 


The  trypanosome  infection  occurs  extensively  among  the  rats  of  many  ||_ 
regions.     In  other  animals  these  trypanosomes  do  not  appear  to  develop. 
The  infected  rats  are  apparently  healthy,  yet  epidemics  occur  in  which 


Fig.  531. — Trypanosoma  {hcrpetosoma)  lewisi  in  the  blood  of   the  rat.     (From  Doflein   after 
Rabinowitsch  and  Kempner.)     Er,  Erythrocytes. 


great  numbers  of  them  die.  Intraperitoneal  inoculations  of  rats  are 
followed  by  a  multiplication  of  the  trypanosomes,  partly  in  the  abdom- 
inal cavity  and  partly  in  the  blood.  According  to  Eabinowitsch  and 
Kempner  reproduction  takes  place  partly  by  longitudinal  and  transverse 
division  of  flagellated  individuals,  and  partly  through  the  segmentation 
of  large  non- flagellated  forms  in  which  the  cell-division  is  initiated  by 


Fig.  .5:53.— Tn/2w«osomn,  {hcrju'tdmnnas)  lewisi,  in  different  stages  of  development.  (After  A.  von 
Wa,sielewski.)  ^1,  Kiilly  ilevfloiicd  piirasite  with  nucleus  (rt),  rod-shaped  body  (ft),  undulating  mem- 
brane (c),  and  flagelliiiii  id)  ;  /;,  |i;ir:isiic  with  twci  iiuclei  and  one  rod-shaped  body;  C,  parasite  with  one 
nucleus  and  two  ni<l-sli;[|icii  limlics;  I),  divisiiin  into  two  parasites;  E,  parasite  With  four  nuclei  and  four 
llagella;  i'',  daughter-individuals  still  united  into  a  colony.      X  1,50U. 

a  division  of  the  nucleus  by  them  designated  as  the  chromatin  framework, 
Avhile  new  nucleoli  are  snared  off  from  the  chromatin  mass.  According 
to  von  Wasielewski  the  chief  nucleus  (B)  sometimes  flrst  divides,  at 
another  time  the  rod-shaped  root  of  the  flagellum  or  the  blepharoplast 
(C) ;  and  the  cells  sometimes  divide  with  two  nuclei  (D),  and  sometimes 


TR  Y  PA  X  OS( )  M  ES .  697 

after  the  formation  of  several  nuclei  and  llanellum -roots  (A',  /•'),  so  iluil 
the  resultiii,!;-  ilividinc:  tlaj^ellates  remain  for  some  tiiiu'  niiUcd  into  c.ln 
nies.  The  natural  iiifeeiion  of  lats  occurs  i)rol):il>ly  tliioii.uli  tin-  mtMliiiin 
of  fleas  and  lice. 

Trypanosoma  brucei,  JMimmcr  and  r.radford,  is\rr\  similar  to  7V. 
kwm,  only  the  body  is  somewhat  hroadcrand  the  ]>ostcri<>r  end  somewhat 
blunter.  It  is  the  cause  of  Nagana  or  the  tsetse-fly  disease  of  cattle, 
horses,  antelopes,  bulfalo,  donkeys,  dojis,  sheep,  and  j^oats  occnnin-;  in 
Southern  and  Southeastern  Africa,  which  is  transmitte<l  lhrouj,di  (lie 
isetse-fly  (GJoxsina  morsitam).  The  nundjer  of  parasites  in  the  biootl  may 
be  very  great ;  the  infected  animals  snlfer  from  fever  and  become  amemic; 
oedema  develops  in  different  parts  of  their  bodies;  fnitlier,  there  is  also 
a  conjunctivitis  and  the  spleen  is  <;reatly  swollen.  The  ]»eiiod  of  incu- 
bation is  not  more  than  nine  days.  The  inf\'cted  animals  die  after  one 
and  one-half  to  eight  months. 

It  is  also  probable  that  the  disease  known  as  Surra,  occnning«'ndenii- 
cally  in  horses,  mules,  camels,  buffalo,  cattle,  and  elephants  in  Dutch 
India,  Indochina,  and  the  Philii^pines,  and  which  is  transmitted  by  gad- 
flies, is  due  to  this  trypanosome.  It  is  likewise  regarded  as  the  cause  of 
the  trypanosome  disease  of  horses  and  donkeys  known  as  tlu'  coitus-dis- 
ease or  dourine  occurring  in  Algiers,  Southern  Ftjuh-c,  Sumatra,  Xovarra, 
and  the  Pyrenees,  and  which  is  spicad  l)y  coitus,  and  is  in<iculable  into 
rabbits,  rats,  and  dogs.  Many  authors  regard  the  i)arasites  found  in 
these  diseases  as  representing  different  species,  giving  to  th«^  first  the 
name  of  Trypanosoma  evansi  and  to  the  latter  that  of  Tr.  <'<{i(iprnliim.  A 
variety  of  trypanosome  found  in  Central  South  America  and  which  causes 
the  disease  of  horses  known  as  mal  de  caderas  is  designated  Tr.  rquiintm. 
It  is  assumed  that  Stoinox!/,s  calcitrans  acts  as  the  agent  of  tiansmissicm  of 
the  parasite. 

A  variety  of  trypanosome  known  as  Tr.  ///^/,V;-Ms  found  in  cattle  in 
South  Africa  and  is  inoculal)le  only  into  this  animal. 

The  occurrence  of  trypanosomes  in  man  was  lirst  obseixed  by  ]^ep- 
veu  (1S9S).  The  investigations  of  recent  years  (Dutton,  Todd,  Jioyce, 
Boss,  Sherrington,  Bruce,  Castellani,  Manson,  Daniels,  Laveran.  etc.) 
have  shown  tliat  trypanosome  diseases  occur  also  in  man.  The  sleeping- 
sickness  of  tlie  negro  is  now  knowntobeduetoatrypanosctme  intrdinn. 
Castellani  found  the  parasite  in  the  cerebrospinal  lluid  of  cas«'s  of  sleep- 
ing-sickness, and  his  findings  have  since  be«'n  <'ontlrme(l  ])y  dinei<'nt 
observers.  The  disease  occuis  throughout  tiojjical  West  Africa,  and  in 
recent  years  has  spread  thi'oughout  Central  and  Eastein  Africa.  Negi-oes 
are  chiefly  affected,  but  cases  have  also  been  obseived  in  Kuiopeans. 
The  infection  is  transmitted  by  a  bit  ing-liy  ( Glossina  palpalis).  The  para- 
sites develop  first  in  the  blood,  and  during  this  i)eiiod  symi)toms  may  be, 
entirely  wanting,  or  there  may  be  attacks  of  fevei-.  ^^'hen  tiie  ]»arasites 
gain  access  to  the  cerebrosi)inal  lluid  and  there  inci«'ase,  ceiebral  symp- 
toms, particularly  conui,  aie  i)roduced  as  the  icsult  of  a  meningitis. 
The  disease  runs  a  chronic  course  and  is  invaiiably  fatal. 

Trypanosomes  are  found  also  in  the  diseast;  known  as  Qamba-fever 
which  occurs  in  Senegambia  and  the  Congo,  both  in  the  natives  and 
Europeans.  According  to  Lav<'ran,  it  is  due  to  the  same  species  of  try- 
panosomes observed  by  Castellani  in  Uganda.  Further,  tryi)anosonM-s 
are  believed  to  be  the  cause  of  the  chronic  diseas*^  known  as  tropical 
splenomegaly,  which  occurs  in  India,  China,  Arabia,  Egypt,  and  'i'unis, 
and  is  characterized  by  intermittent  or  remittent  attacks  of  fever  a.ssoci- 


698  THE    ANIMAL   PARASITES. 

sited  w  itli  a  marked  swelling  of  the  spleen,  leading  after  many  months' 
duration  to  a  in-ogressive  anaemia  and  cachexia  having  a  fatal  termina- 
tion, and  therefore  distinguished  from  the  ordinary  malarial  fe\  ers  by 
the  designation  of  cachectic  fever.  It  is  very  probable  that  the  disease 
known  as  Kdla-azdr  (black  fever),  which  is  widely  distril>uted  through 
the  valley  of  Assam  watered  by  the  Brahmaputra,  and  is  often  character- 
ized by  dark  discoloration  of  the  skin,  is  related  to  troi^ical  splenomegaly. 

The  life-history  of  the  trypanosomes  is  similar  to  tliat  of  the  spirochaetes. 
According  to  investigations  by  Schaudinn  the  Halteridia  {IIcBmoproteus  noduce  of  Celli 
and  San  Felice)  of  the  Httle  owl  are  the  sexual  stages  of  a  tr^^aanosome  which  multiplies 
in  the  common  mosquito,  Culex  pipiens,  so  that  after  a  complicated  wandering  through 
the  body  of  the  mosquito,  through  its  bite  again  reaches  the  blood  of  the  owl,  in  which 
after  a  period  of  asexual  increase  it  changes  into  the  familiar  male  and  female  Halteridia. 
The  parasite  must,  therefore,  be  called  the  Trypanosoma  noctuce.  (Whether  other 
members  of  the  genus  Halteridium  or  Hsemoproteus  are  to  be  classed  with  the  trypano- 
somes remains  to  be  settled.)  According  to  Xovi/  {Jour,  of  Infect.  Dis.,  1905)  the 
observations  of  Schaudinn  are  open  to  an  entirely  different  interpretation.  He  believes 
that  the  Trypanosoma  noctuce  and  the  Spirochceta  zienmnni  of  Schaudinn  probably 
represent  trypanosomes  that  have  multiplied  in  the  mosquito  and  are  not  to  be  con- 
sidered as  stages  in  the  life-history  of  cytozoa.  According  to  Novy's  investigations 
trypanosome  infection  of  birds  is  very  widespread.  With  the  tr^-panosomes  there  may 
be  associated  intracellular  parasites,  but  no  constancy  can  be  shown  to  exist  between 
a  given  trypanosome  and  a  given  cytozoon.  The  life-cycle  of  the  trypanosomes  and 
halteridia  according  to  Schauditm.,  as  given  in  the  follo\\ing  paragraphs,  cannot,  there- 
fore, be  accepted  without  question  in  the  light  of  Novy's  work. 

If  the  male  and  female  halteridia-stages  enter  with  the  blood  of  the  owl  into  the 
intestine  of  the  mosquito,  the  first  forms  the  microgametocytes  and  microgametes,  each 
of  which  penetrates  into  one  of  the  pigment-containing  macrogametes.  As  the  result 
of  this  fertilization  the  latter  become  changed  into  ookinetes.  Through  a  complicated 
metamorphosis  proceeding  from  the  nucleus  the  ookinete  can  become  transformed  into 
an  indifferent  trypanosome.  The  karysome  passing  out  from  the  nucleus,  and  which 
has  the  significance  of  a  nucleus,  moves  to  the  right  lateral  border  of  the  ookinete  and 
forms  there  the  blepharoplast  of  the  trypanosome,  that  is,  the  structure  which  forms 
the  undulating  membrane  and  the  flagella.  The  trypanosome  thus  formed  can  increase 
by  longitudinal  division. 

The  ookinetes  can  also  form  female  trypanosomes  which  are  plumper  and  show  a 
more  marked  granulation  than  the  non-.sexual  forms.  The  female  trypanosomes  repre- 
sent permanent  forms,  and  can  produce  new  generations  in  the  mosquito  through  par- 
thenogenesis. Finally,  the  ookinete  can  also  be  transformed  into  a  male  trj'panosome 
which  is  smaller  and  clearer  than  the  female.  Through  heterotopous  mitosis  there  may 
be  formed  in  both  the  female  and  male  trj'panosome  a  small  nucleus  near  the  large  one, 
and  this  may  increase  until  as  many  as  eight  are  formed.  While  in  the  female  these 
are  destroyed  and  only  the  chief  nucleus  is  preserved,  each  of  the  eight  nuclei  develops 
in  the  male  into  a  blepharoplast  from  which  a  minute  male  trypanosome  arises. 

The  development  of  the  microgametes  in  the  blood  of  the  owl  takes  place  in  the 
same  manner  as  the  formation  of  the  male  trypanosomes  in  the  intestine  of  the  mosquito, 
and  they  have  the  same  structure  as  the  latter.  The  indifferent  try])anosomes  passing 
from  the  mosquito  into  the  blood  of  the  owl  are  usually  very  small.  They  fasten  them- 
selves by  their  flagellated  anterior  end  to  the  red  blood-corpuscles;  the  flagellum  ap- 
paratus then  degenerates  and  the  parasite  takes  on  the  appearance  of  a  sickle-shaped, 
bean-  or  worm-shapc-d  halteridium.  When  it  has  about  doubled  its  size,  it  leaves  its 
host  and  again  develops  a  flagellutn-ajiparatus,  becoming  changed  again  into  a  trypano- 
some. This  is  repeated  several  times  until  a  certain  size  is  attained;  there  then  follows 
a  multiplication  through  longitudinal  division,  the  products  of  the  division  again  seeking 
red  blood-cells. 

The  fully  formed  female  trypanosomes,  the  macrogametes  in  the  owl's  blood,  are 
shaped  like  little  worms;  they  penetrate  the  red  blood-cells  and  deprive  them  of  their 
haemoglobin.  They  represent  permanent  forms  and  after  a  long  interval  can  produce 
new  generations  by  means  of  parthenogenesis.  The  male  microgametocytes  arise  in  the 
blood  from  indifferent  forms  and  produce  eight  microgametes  as  in  the  intestine  of  the 
mosquito.  The  rii:)ening  of  the  macrogametes  and  their  fertilization  by  microgametes 
take  place  in  the  intestinal  tract  of  the  mosquito. 

It  has  not  been  positively  decided  at  the  present  whether  human  trypanosomiasis 
is  due  to  more  than  one  variety  of  trypanosome.     The  different  clinical  course  of  the 


TinPANOSOMKS.  699 

affections  makes  this  probable.  In  the  forms  known  as  troptail  splctwmrqubi  or  mrhcctir 
fever  aiu\  kiUn-azdr  there  are  fonml  (Lcislunan,  Marrluuxl)  in  I  lie  s|)i(Tn.'  liver,  bone- 
marrow,  Ijniiph-nodes,  and  also  in  intestinal  nlcers  j^reat  numbers  of  smjili  bodies,  partly 
free  and  partly  intracellular,  consistinj;  of  an  intensely  stainiufj  rin<;-shaped  chroiii.ntiii 
body  surrouiuletl  by  a  circular  or  oval,  clear  area  staininj;  li<;htlv  with  eosin.  Hesi<le.s 
the  chromatin-body  there  is  often  found  also  (MdirlKuul,  LnUuqiuim)  a  small,  intensely 
staining  round  or  elon<;;ated  granule,  which  is  often  connected  with  the  chromatin-rinK 
by  a  delicate  stalk.  These  bodies  ("  Lci^lnmin-Dnnovan  baiUca  ")  were  first  found  by 
Leishman  and  Donovan  in  smears  made  from  the  spleen,  and  were  later  studied  by 
Marchand,  Ledingham,  Mansori  aiul  Low,  BrntUn,  lioijcri^.  and  others,  and  wem  ^iveu 
different  interpretations,  the  general  opinion  beiiig  that  they  represented  degeneration 
forms  of  trj^xinosomes.  Roycrs  has  succeeded  in  growing 'them  outside  of  the  body 
and  in  demonstrating  their  transformation  into  elongated  flagellated  organisms  resem- 
bling trypanosomes.  On  account  of  the  absence  of  an  undulating  membrane  lingers 
believes  the  organism  to  be  a  herpetomonas.  Rons  regards  it  as  a  new  genus  ami  has 
called  it  Lcishmani  donovani.  Nothing  is  yet  absolutely  determined  concerning  the 
transmission  of  this  fatal  infection.  Rot/crs  believes  that  it  is  transmitted  l)y  bed-bugs 
or  mosquitoes.  Very  recently  Xicolle  (ArcJi.  dc  I'Inst.  Pasteur,  Timis,  19()S)  has  suc- 
ceeded in  cultivating  the  Leishman-Donovan  bodies  from  cases  of  infantile  sjtlenomeijalij 
in  Tunis.  He  regards  the  protozoon  obtained  as  a  new  species,  Leishnutnia  in/anlum. 
The  protozoa  found  in  a  case  of  tropical  sore  by  Wright  {Jour,  of  Med.  Res.,  Ukv.i)  and 
called  by  him  Helcosoma  tropicum,  are  regarded  as  Leishmai-.-Donovan  bodies,  and 
designated  by  Nicollc  as  Leishmania  wrighti.  They  are  to  be  regarded  as  the  infective 
agent  of  "Delhi  boil." 

According  to  the  majority  of  writers  trypanosomc  or  Gamhian  fever  is  but  the  early 
stage  of  sleeping-siekness,  both  conditions  being  due  to  infection  with  the  .same  parasite, 
the  Trypanosoma  gambiense.  The  first  stage  is  of  a  variable  duration,  lasting  from 
three  months  to  three  years  or  longer.  During  this  stage  there  is  a  polyadenitis  and  the 
trypanosomes  may  be  demonstrated  in  the  blood  and  Ijaiiph-nodes.  As  a  diagnostic 
method  the  examination  of  a  drop  of  fluid  removed  from  an  enlarged  cervical  gland  by 
means  of  a  hypodermic  needle  is  advised,  since  the  jjarasites  can  be  found  in  this  way 
immediately  if  they  are  pre.sent  in  the  hoAy. 

According  to  the  views  of  many  authors  it  is  probable  that  yellow  fever  is  a 
protozoan  disease,  although  the  parasite  has  not  yet  been  demonstrated.  Srhaudinn 
showed  that  trypanosomes  in  certain  stages  formed  such  small  individuals  that  they 
could  not  be  recognized  singly  under  the  microscope.  He  would  seek,  therefore,  the 
yellow-fever  parasite  among  the  flagellates.  Yellow  fever  is  endemic  in  the  Antilles, 
Southern  States  of  North  America,  Brazil,  east  coast  of  South  .\merica,  and  in  many 
parts  of  West  Africa.  As  the  result  of  the  work  of  a  United  States  Connnission  consist- 
ing of  Rce'f,  Carroll,  Agramonte,  and  Lazear,  it  was  determined  in  1900  that  yellow  fever 
is  transmitted  only  through  the  bite  of  a  mosquito  (Stegoniyia  faseiata) .  Subcutaneous 
inoculation  of  the  blood-serum  of  a  case  of  yellow-fever  into  a  non-immune  during  the 
first  three  days  of  the  disease  will  transmit  the  infection.  The  mosquito,  therefore, 
to  become  infected  must  suck  the  blood  of  a  patient  during  this  time.  The  bite  of  the 
mosquito  does  not  become  dangerous  imtil  twelve  days  after  taking  up  infected  blood, 
so  that  it  is  apparent  that  the  parasite  must  undergo  a  further  tlevelopment  within 
the  body  of  the* mosquito.  The  latter  is  able  to  infect  after  this  period  as  long  as  it  lives. 
Navy  believes  that  the  cause  of  yellow  fever  will  be  found  to  be  a,. "Spirillum. 

The  first  successful  cultivation  of  a  pathogenic  protozofin  anil  the  (lemonstration 
of  its  relation  to  the  disease  by  the  infection  of  j)urc  cultures  were  attained  by  Nury 
and  McNeal  in  the  case  of  Trypanosoma  letrisi  and  later  of  Tr.  hrucei. 


Literature. 

( Tr;/j)(iii(>.soiiii.s. ) 

Baker:  Trypanosoma  in  Man.     Brit.  Med.  .lourn.,  i..  190:^. 

Bradford  and  Plimmer:  The  Trypanosoma   Jirucei.     (^uart.  .lour,   of  .Micr.  Sc.  .\lv., 

1901.  .     . 

Bruce:  Rep.  on  the  Tsetse  Fly  Disease.     Ubombo,   1S9.')  and  l,S9(i;  '1  rypanosonuasis. 

Brit.  Med.  .Journ.,  ii.,  1901. 
Bruce,  Nabano,  and  Greig:  The  Ktiol.  of  Sleeping  Sickness,     lint.   .Mi-d.  .lourn.,  n., 

190.3. 
Byloflf:   Rattentrj-panosomen.     Sitzungsbericht  d.  Kaiserl.  Akademie  m  W  icn,    cxni., 

1904. 


700 


THE    ANIMAL    PARASITES. 


Carini.    Die  pathogenen  Trj^ianosomen.     Korrbl.  Schweizer  Aerzte,  1904. 
Castellani:  Aetiologie  der  Schlafkrankheit.     Centralblatt  furBakteriol..  Orig.,  xxxv., 

1903. 
Danielewsky:  Z.  Parasitologie  desBlutes.     Biol.  Cbl.,  v.,  1886;    La  parasitoiogie  du 

sang.     Charkoff,  1889. 
Doflein:  Die  Protozoen  als  Parasiten  und  Krankheitserreger,  Jena,  1901  (Lit.). 
Doflein  and  V.  Prowazek:  Die  pathogenen  Protozoen.  Handb.  d.  pathog.  Mikroorg., 

i.,  1903  (Lit.). 
Donovan:  The  Etiology  of  One  of  the  Heterogeneous  Fevers  of  India.     Brit.  Med. 

Journ.,  ii.,  1903. 
Dutton:  Trj'panosoma  Occurr.   in  the  Blood  of  Man.     Thompson- Yates  Lab.  Rep., 

iv.,  1902. 
Dutton  and  Todd:  Rep.  to  the  Trypanosomiasis  Exped.  to  Senegambia.    Thompson- 

Yates  Lab.  Rep.,  v.,  1903. 
Elmassian  et   Mogune:  Sur   le   mal   de   Caderas.     Annales   de   ITnstitut    Pasteur, 

19J3. 
Giinther:  Trypanosomen  bei  Menschen.     Miinch.  med.  Woch.,  1904. 
Kasewurm  u".  Steinbruck:  Tier.  Paras,  bei  Haustieren.    Ergebn.  d.  allgem.  P.,   viii., 

1904. 
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Reiseberichte  iiber  Rinderpest,  Bubonenpest,  Tsetse-  oder  Surrakrankheit,  Texas- 

fieber,    tropische    Malaria,    Schwarzwasserfieber,    Berlin,    1898;     Trypanosomen- 

krankheit.     D.  med.  Woch.,  1904. 
Lang:  Protozoen,  Jena,   1901. 
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somiase  humaine.    Compt.  rend,  de  I'Ac.  d.  Sc,  cxxxviii.,  1904. 
Laveran  et  Mesnil:  Maladie  de  la  mouche  tsetse.     Ann.   de  ITnst.  Pasteur,   1902; 

Trypanosomes  et  Tryj^anosomiases.     Paris,  1904. 
Leishman:  On  the  Possibility  of  the  Occurrence  of  Trypanosomiases  in  India.     Brit- 

Med.  Journ.,  i.,  1903,  p.  1252;   Discussion  on  the  Leishman-Donovan  Bodv.     Tli., 

ii.,  1904,  p.  642. 
Lignieres:  Mal  de  Caderas.     Ref.  C.  f.  Bakt.,  xxxiv.,  1904. 
MacNeal:  The  Life-history  of  Tr.  Lewisi  and  Tr.  Brucei.     Journ.  of  Infectious  l)is.. 

!>U4. 
Manson  and  Daniels:  A   Case  of  Trypanosomiasis.     British  Medical  Journal,    i., 

19U3. 
Marchand  u.  Ledingham :  Ueber  Infektion  mit  Leishmanschen  Korperchen.     Z.  f. 

Hyg.,  47  Bd.,  1904  (Lit.). 
Marchoux:  La  fievre  jaune.     Ann.  de  I'lnst.  Pasteur,  1903. 
Nepveu:  Trypanosome  dans  le  sang  de  I'homme.     Compt.  rend.  Soc.de  Biol.,  Paris, 

IS'JS. 
Novy:  The  Trypanosomes  of  Tsetse  Flies.     Journ.  of  Infect.  Dis.,  1906. 
Novy  and  MacNeal:   Cultivat.    of  Trypanosoma  Brucei.     Journ.   of   Infect.  Dis.,  i., 

Chicago,  1902,  u.  Biol.  Cbl.,  xxiv.,  1904;    On  the  Trypanosomes  of  Birds.     Journ. 

of  Infect.  Dis.,  190.",. 
Novy,  MacNeal,  and  Torrey:  The   Trypanosomes  of  Mosquitoes.     Journ.  of  Infect. 

Uis.,  1907. 
Plimmer  u.  Bradford:  Morphologie   des   Tsetseparasiten.     Cbl.    f.    Bakteriol.,   xxvi., 

1899. 
Rabinowitsch  u.  Kempner:  RattentrjTianosomen.     Z.  f.  Hyg..  .30  Bd.,  1899  (Lit."); 

Trvpanosomen  in  dcr  Menschen-  u.  Tierpathologie.     C.  f.  B.,  Orig.,  xxxiv.,  1904 

(Lit.). 
Rattig:   Ueber  Parasiten  des  Froschblutes.     I.-D.,  Berlin,  1875. 
Rieck;  Sporozoen  als  Kranksheitserreger  bei  Tieren.     Deutsche  Z.   f.  Tiermed.,  xiv., 

1.SS9. 
Rouget:  Trypanosomes  des  mammiferes.     Ann.  de  ITnst.  Pasteur,  1896. 
Ruge:  Ueber  das  deutsche    Proteosoma    (bei   Sperlingen).     C.    f.    Bakteriol.,  xxix., 

1901. 
Salmon  and  Stiles:  Rep.  on  Surra:    XVIII.  Ann.  Rep.  of  the  Bureau  of  Animal  In- 
dustry, Washington,  1902. 
Schaudinn:  Generations- u.  Wirtswechsel  bei  Trypanosomen  u.  Spirochiiten.     Arb.  a. 

;i._K.  Gesundheitsamte,  xx.,  1904. 
Schilling:  Surrakrankheit  der  Pferde  u.  Rinder  in  Togo.  C.  f.  Bakteriol.,  xxxi.,  Orig., 

1902. 
Voges:  Mal  de  Caderas.     Z.  f.  Hyg.,  39  Bd.,  1902. 
Wasielewski  u.  Senn:  Flagellaten  des  Rattenblutes.     Zeitschr.  f.  Hygiene,  33  Bd., 

1900. 


Wittich:  Spiii 
1S91. 


COCCI D I  \.  701 

iin  Bluto  von    llausliiMvii.      CtMitrMll.l.    f.    ,li.'    nic.l.    W  isscMsrlmft. 


§187.  Of  tlu'  Sporozoa  oecuiTinj;^  as  ])arasilcs  in  man  and  in  the 
mammals,  11  it' coccidia  aio  to  be  uuMitioiuHl  liisl.  In  their  ><)nn-  stair 
they  exist  as  iion-oiieapsulated  inhabitants  of  i'pitlitlial  rdls,  particularly 
iu  those  of  the  intestinal  eaual  and  its  adnexa,  tlu-  li\cr  especially,  and 


Fig.  533.— Section  through  the  wall  of  a  dilated  bile-duct,  tilled  with  coccidia  and  lined  with  papillary 
proliferations.  From  a  rabbit's  liver  that  was  studded  with  coccidia  nodules  ( Miiller's  iluid,  ha-nintoxylin, 
eosin).  a.  Connective  tissue;  b,  branching  papillary  proliferations  covered  with  epithelium;  c,  cocddla. 
X23. 


more  rarely  in  those  of  the  organs  of  excretion.  Some  of  the  mature 
forms  surround  themselves  with  a  capsule  and  become  changed  into 
rounder  oval  jjennanent  cysts  or  ooc?/6fs  (Schaudinn),  which  leave  their 
resting-place  and  usually  also  their  host,  and  under  certain  conditions 
form  sickle-shaped  sporozoites  through  the  rejieated  division  of  their 
cell  body  {sporogony).  Through  the  taking-up  of  siioi-ozoite-containing 
oocysts  into  a  new  host  there  is  produced  an  infection  of  the  latter,  in 
that  the  sporozoites  are  set  free  and  seek  out  epithelial  cells  f(.i-  their 
further  development. 

Besides  this  form  of  multiplication  there  occurs  within  the  infected 
organ  also  a  reproduction  by  schizof/ony — that  is,  there  are  develojied 
from  mature  hut  non-encysted  individuals,  by  means  of  .segnuMitation, 
a  large  nuinl)er  of  new  sickle-sha]»ed  indi\id- 
uals,  the  so-called  mrrozDifcs,  m  hich  seek  out 
epithelial  cells,  and  de\elop  furl  her  in  the 
same. 

Coccidium  oviforme  ( I'ig.  ."i.)  I )  is  a  jiara- 
site  of  the  intestine  and  biliary  passages, 
occurring  especially  in  rabbits.  Kiinsllei- 
and  Pitres  found  similar  coccidi;i  in  man  in 
a  i)lenritic  exudate.  Podwyssozki  claims  to 
have  observed  them  in  the  lmm;in  liver. 

In  the  liver  of  rabbits  the  invasion  of 
coccidia  leads  to  the  formation  (tf  while 
nodules  which  may  reach  the  size  of  a  h;izel 
nut,  and  are  designated  as  rorcidiainnlnlrs. 
These  nodules  conl:iin  a  soft,  while,  or  yel- 
lowish-white mass,  and  consist  essentially  of 


from  It 


sv.iiii-s  of 


Fig.  rM.-Cncc 

duct  of  ihe  labh 
Showing  difTcn-u 

ment  (Muller's  Iluid,  ha>niatoxylin). 
a.  h.  Small,  coarsely  granular  young 
forms;  c,  rf,  large  forms  with  darkly 
staining  peripheral  granules;  e, /,  g, 
h,  oval,  encapsulated  forms,  the  pro- 
toplasm of  which- partlv  coarsely 
granular  and  parti v  line- fills  up  only 
a  portion  of  the  capsule.    X  400. 


702  THE    ANIMAL    PARASITES. 

dilated  bile-passages,  the  inner  surface  of  which  is  more  or  less  richly 
furnished  with  papillary  growths  (Fig.  533),  and  whose  lumen  contains 
great  numbers  of  coccidia. 

The  coccidia  occur  in  the  bile-passages  partly  in  the  form  of  non-encap- 
sulated protoplasmic  structures,  and  partly  in  the  form  of  encapsulated 
bodies.  The  smallest  coccidia,  which  are  regarded  as  the  younger  forms, 
exhibit  a  coarsely  granular  protoplasmic  structure  (Fig.  oo^,  a,  h), 
within  which  a  nucleus  («)  may  occasionally  be  demonstrated.  The 
larger  forms  exhibit  on  their  outer  surfaces  regularly  arranged  granules 
(e,  d),  which  stain  intensely  with  hrematoxylin.  The  encapsulated  forms 
occur  as  oval,  doubly  contoured,  clear  bodies  (f, /,  g,  h)  within  which 
lies  a  variously  shaped  mass  exhibiting  also  various  forms  of  granulation, 
but  never  entirely  filling  up  the  space  within  the  capsule. 

To  the  coccidia  belong  probably  also  those  parasites  which  occur  in 
the  epidermis  of  man  and  form  there  peculiar  growths  known  as  epithe- 
lioma contagiosum  (Fig.  535).  In  its  fully  developed  condition  the 
growth  consists  of  a  small  nodule,  about  the  size  of  a  pea  or  larger, 
which  is  elevated  above  the  surface  of  the  skin,  shows  a  small  groove  in 
its  centre,  and  possesses  a  waxy  lustre. 

On  section  there  may  be  seen  a  lobulated  epithelial  growth  (Fig.  535, 
d),  with  a  central  cavity  opening  externally  {g),  thus  forming  a  growth 
resembling  a  gland;  and  it  has  been  many  times  mistaken  for  a  hyper- 
trophic sebaceous  gland.  It  therefore  represents  an  independent  new- 
formation  of  epithelium  due  to  a  parasite.  The  parasites  develop  inside 
of  the  epithelial  cells  of  the  lobulated  growth  (e),  but  are  pressed  by  the 


-^-^ 
^:£^- 

FiK.  535.— Epithelioma  com  ijriosum  Se(  tion  tlirousrti  }rie  ito^t  diaitiett  r  (Miiller's  fluid,  htpmatoxylin). 
a.  Epidermis:  h,  connective  tissue  (  selndoub  ^l.md  d  fri  md  like  epitt  t  lial  prolii'erations  ;  e,  para- 
sites;/, borny  cells  min^ltd  \\ itli  p  ir isiu  s ,  (/  due  t  lUled  with  lioru>  t  pithi  liiim  and  parasites.     X  13. 

growth  of  the  adjacent  epithelium  toward  the  central  cavity  of  the  new- 
formation  (/),  and  lie  there  in  a  mesh  work  of  desquamated  and  horny 
epithelial  cells. 

The  earliest  stages  of  development  of  the  parasites  occur  in  the  epi- 
thelial cells  as  small  protoplasmic  bodies  (Fig.  53C,  o,  />),  which  can  be 
distinguished  from  the  cell-protoplasm  only  with  difficulty;  occasionally 
they  contain  in  tlieir  interior  small,  distinct  granules,  and  are  therefore 
more  evident.  Later  they  increase  in  size,  and  finally  fill  up  completely 
the  epithelial  cell  (c,  d,  ^e),  pressing  the  nucleus  to"^  one  side.  At  the 
same  time  the  granules  within  the  cell  (c)  increase,  and  grow  to  larger 
bodies,  so  that  the  parasite  finally  becomes  divided  into  a  greater  or  less 
number  of  M-ell-defiued  structures  (,/,  e,  f)  lying  in  a  finely  granular 


SAKC'OSrOKlDlA. 


7():j 


Fk;.  o3t).^Parasitasof  Epitlieliojjiacontjuriosuiii  in  va- 
rious staires  of  (ievelopuieiit.  lying  inside  cpithfliiil  cells 
(Miilier'stluid.  Inviiiatuxvlin).    <t.  h.  Epithelial  cells,  en- 

ckisinir  a  iimtdi'lasmic  liodv  in-ide  of  winch  lie  siiifrle 
larirc  LTanulcs:  r.  cpitliclial  cell  alninst  <'i.ii!!ileielv 
lined  Willi  parasites:  <l.  ,.l,  parasites  coiiipletely  llllintr 
the  epithelial  cells,  and  divided  into  uuuieious  separate 
iHHlies  lyinj?  in  a  granular  network  ;  the  cell-nucleus 
has  been  destroyed  in  /.    X  about  500. 


lu'twoik.  The  micU'Us  of  tlir 
t'pillicliaU'dl  isdcslroycddiii  iii^ 
(his  t  iiMc. 

Tlic  cpillK'lial  cells  Mliichcii 
close  i)arasitcs  (.l('\«'l(i|>  early  a 
(lislinct  ineiiibraiie,  wliicli  he 
comes  more  ami  moi-*'  eleaily 
(k'tiiied,  and  suiioiiiids  the  paia 
site.  The  ])arasites  which  aic 
expelled  from  the  cells  form 
oval  bodies  Mhich  ai)itear  en- 
closed ill  a  ea])suleaii<l  i>reseiit  a 
liomofi'eneons  api)earance.  They 
slain  deei>ly  with  luematoxylin. 

The  contagious  epitheliomata 
may  appear  in  i;reat  mnnhers  in 
one   and    Die    same    in(li\  idual, 

to- 

The 


and  several  persons  li\ 
aether  may  be  either  sinmltaueously  or  successively  attacked 
spread  of  the  disease  is  therefore  referred  to  a  coutagioii. 

By  many  writers  the  moUuscum  bodies  are  not  believed  to  be  parasites,  but  -.wo 
regarded  as  hyaline  or  horny  products  of  cell-degeneration. 

Our  knowledge  of  the  significance  of  the  so-called  Miescher's  sacs 
is  still  incomiDlete.  They  are  tube-shaped  struct uies  Avhich  aic  imt 
infrequently  found  in  the  muscles  of  the  hog  (Fig.  537,  a,  b),  cattle, 
sheep  (especially  in  the  oesophagus),  and  mice.  They  vary  in  size,  and 
lie  within  the  muscle-fibres.  In  mature  ])arasites  the  contents  of  the 
tuljes  are  differentiated  into  single  segments  delined  by  a  mend)iaue 
(Fig.  537),  which  enclose  spherical  (r),  kidney-shaited,  or  sickle-shaped 
bodies.  The  parasite  is  classed  with  the  Sarcosporidia.  The  sejjarate 
.segments  are  designated  sporocysts  or  sporohhixtx,  since  within  the.se  the 
round  or  sickle-shaped  spores  (Eaincy's  bodies)  arise.     From  the  latter. 


f-^' 


Kir,.  .5:i7.— Miescher's  sacs,  from  swine-muscle,    n.  h.  Muscle  cut  lonjrltudlniilly  and  transvenu'ly.    X  \n\ 
c,  I^ongitudinal  section.     X  "iH«. 

new  Miescher's  sacs  may  develop  under  favorable  conditions  (IM'einer). 
Ingestion  of  meat  containing  sarcosporidia  is  not  <laiigerous  for  man,  bm 


704 


THE    ANIMAL      PARASITES. 


sarcocysts  have  been  observed  in  mau  in  tlie  ninscles,  heart,   intestine, 
and  liver  (Lindeuiann,  Koch,  Kartulis,  Eosenberg,  and  others). 

As  early  as  1870  Eimer  published  observations  of  the  development  of  coccidia,  but 
their  life-historj'  has  been  accurately  determined  only  in  recent  years,  through  the  in- 
vestigations of  R.  Pfeiffer,  Simond,  Llger,  Schaudinn,  Schuberg,  Siedlecki,  Schneider,  von 
Wasielcu-ski,  Labbr.  and  others.  ^ 

Tlie  reproduction  of  coccidia  occurs  (Lilhe)  partly  through  sporogony,  partly 
through  schizogony.  The  first  method  serves  for  the  spreading  of  infection  and  the 
preservation  of  the  species,  the  second  increases  the  extent  of  the  infection  within  the 
infected  host.  Sporogony  is  closely  connected  tcith  a  previously  occurring  copidation 
which  in  its  course  suggests  the  fertilization  of  the  egg  of  the  metazoa.  An  alternation 
of  generations  also  takes  place. 


7^^^ 


53- 


Fig.  538.— Cycle  of  development  of  Coccidtum  Schubergi.  (After  Schaudinn  and  Liihe).  1,  Sporo- 
zoite  (or  merozoite)  penetrating  into  an  epithelial  cell ;  2,  mononuclear  schizont  in  an  epithelial  cell ;  S, 
multinuclear  schizont ;  4,  division  of  the  schizont  (schizogony)  into  numerous  merozoites ;  5,  macroga- 
inete  (female  cell)  arising  from  a  merozoite;  6,  fully  developed  macrogamete  surrounded  by  extruded 
chromatin  granules;  5a,  microgametocyte  (male  cell)  arising  from  a  merozoite;  6a,  microgametocyte sur- 
rounded by  loosened  microgametes  (spermatozoa) ;  7,  fertilization  of  the  maerogametes  by  microgametes ; 
s,  young  oocysts ;  9.  oocysts  with  sporoblasts ;  10,  oocysts  with  sporocysts,  each  containing  two  sporo- 
zoites ;  11,  sporozoite. 

The  developmeut  and  reproduction  take  place  in  the  following  manner:  In  schiz- 
ogony the  sickle-shaped  germ  (Fig.  5"^8,  1)  arising  as  a  sporosoite  or  merozoite  develops 
within  an  cpitliclial  cell  into  a  schizont  {3)  in  which  there  soon  takes  place  a  multiplica- 
tion of  the  nucleus  (.;).  There  then  results  (on  the  second  day  after  the  over-feeding  of 
sporocysts)  a  formation  of  merozoites  (^)  corresponding  in  number  to  the  nuclei,  and  a 
residual  body  wiiieli  is  left  behind  after  the  segmentation. 

The  merozoites  again  seek  e]iitiielial  c;ells,  and  the  same  development  begins  anew. 
If  the  affected  organ,  as  the,  result  of  tliese  processes,  becomes  overcrowded  with  para- 
sites, there  are  tiien  formed  sexual  \\\(\\\'u\w,i\?,  {Schaudinn).  Some  of  the  merozoites 
grow  into  large  cells,  the  nuicnxjiiuKicH  (.7,  6)  or  female  cells,  which  when  mature  throw 
off  a  portion  of  their  chromatin-substancc  (6),  and  either  remain  naked  or  surround 
themselves  witii  a  capsule,  which  is  provided  with  a  micropyle.  At  the  same  time 
other  merozoites  develop  into  the  male  sexual  cells  or  microg'ametocytes  {5a,  6a),  the 
nuclei  of  which  divide  into  many  daughter-nuclei.  The  latter  approach  the  surface  of 
the  cell,  and,  surrounded  by  a  certain  amoiuit  of  protoplasm,  are  constricted  off,  (6a) 


PATIKKiKNIC    I'HO'POZOA.  7()-, 

am]  then  represent  tlic  ?»?V;v>.7r/wf^'.9  (ooircspondinir  to  tlic  spcrmato/.oji  of  tlie  lii-ciier 
animals).  The  copuhttion  of  the  inierogainetes  witli  tlic  iiia(  rojrametes  takes  place  "in  ii 
manner  similar  to  that  of  tlie  fertilization  of  the  metazoan  ctri:,  in  tiiat  tiie  niieronauietc 
penetrates  the  encapsulated  form  of  macrouaniete  throu^;h  the  miciopvlc.  niiil  the  naked 
form  through  acertain  point  which  pushes  itself  outward  to  form  a  pron)inrncc(;),tiie 
conceptional  protuberance.  Sponxjoni/  follows  the  fertilization  that  is,  the  o.icysl' (,V) 
is  formed,  in  which,  through  the  division  of  the  nucleus  and  protoplasm,  there  arise 
four  sporoblasts  (//),  each  of  which  later  produces  two  sickle-shaped  si,oro:„il,s  (Im. 

Numerous  authors  hold  the  view  that  other  local  i)alhologi(al  ((.ndilions  of  the 
tissues  in  man  than  those  <leserii)ed  al)ovc  may  i)e  referred  to  .•</«i/vo/.^  jtartieularlv  mr 
einomn,  Jhirur'x  (H.yiiiKC,  J'ii(/e('x  (//.v^/.v,  peculiar  diseases  of  tlie  urinarv  passjincs,  etc. 
It  may,  however,  be  remarked  that  this  assumjition  in  part  is  based  ui)on  error,  aiid  in 
part  has  not  been  absolutely  proved  by  the  investigations  wln'ch  liave  been  made  up  to 
the  present  time. 

So  far  as  carcinoma  is  concerned,  in  spite  of  the  great  number  of  works  on  the  sub 
ject,  so  numerous  indeed  that  they  can  scarcely  l)e  iierused  (cf.  t;  121),  no  ]n-oof  lias  yet 
been  given  that  protozoa,  coccidia  in  particular,  are  iirescnt  within  (he  epithelial  pro- 
liferation and  are  to  be  regarded  as  the  cause  of  the  same.  Ail  the  ap|)i'arances 
described  as  occurring  in  carcinoma  cells,  even  the  sickle-shaped  formations  which  have 
been  thought  to  be  convincing  and  those  provided  with  a  sort  of  caiisule.  may  be  other- 
wise interpreted,  and  maybe  explained  in  part  as  changed  luiclei,  in  jiart'as  alt<'red 
protoidasm  of  the  cancer-cells,  in  i)art  as  cell  excretions,  and  finally  in  part  as  a  jiroduct 
of  cell-fusion  or  of  the  taking  up  of  leucocytes  by  the  cancer  ceHs. 

The  disease  described  hy  Da rier  -a^  iis(',n>siH  nimsr  foil iculaiir  n'rietnuU',  and  referred 
by  him  to  the  presence  of  sporozoa,  is  very  probably  only  an  intlammalory  alTection  of 
the  skin  characterized  by  a  pathological  cornitication  (keratosis  follicularis  of  nm 
Withe),  in  Avhich  little  horny  plugs  and  pegs  are  developed  successively  in  the  epithe- 
lium of  certain  parts  of  the  body,  while  the  cutis  shows  slight  inllanunatory  changes. 
According  to  Buzzi,  Mietlike,  liieck,  Krimng,  Petcrwn,  and  others,  the  "ohjik  ioikIm," 
described  by  Ddiier  as  parasites,  contain  kerotoln'alin  and  eleidin,  substances  which  are 
present  in  cornitied  cells  but  not  in  gregarinft. 

Pallet's  disease  is  an  affection  spreading  from  the  nipple,  beginning  with  an  eczema- 
like inflammation,  and  leading  to  superficial  ulceratitm,  and  finally  ending  in  a  carci- 
noniatous  infiltration  of  the  skin.  It  has  been  referred  by  Daritr.  Wiickham.  Malassez. 
and  others  to  the  presence  of  a  parasitic  sporozoon  in  the  epithelial  cells;  but  is,  how- 
ever, either  an  eczema  arising  from  other  causes,  and  finally  leading  to  cancer,  or  else 
is  a  primary  cancer  accompanied  by  inthmunatory  ])rocesses  {Ehrlnirdt).  in  which  i)ecul 
iar  changes  take  place  in  the  epidermis,  i>artie"u]arly  swelling  of  the  ])roto|ilasm  and 
nuclei,  with  formation  of  vacuoles,  and  further  ])rolii'eralive  changes,  the  peculiar  aj)- 
pearances  of  which  might  be  mistaken  for  parasites.  According  to  Jacohaina  these 
appearances  are  brought  about  through  the  penetration  of  the  carcinoma  into  the 
superficial  epithelium. 

In  variola  and  vaccinia  tliere  occur  constantly  in  the  epithelium  that  has  undr-r- 
gone  recent  changes  small  lightly  staining  bodies  surrounded  by  a  clear  zone,  often  in 
great  numbers.  Their  constant"  occurrence  in  repeated  inoculations  and  their  ehanic- 
teri.stics  make  it  very  probable  that  they  represent  parasites  belonging  to  the  i)rotozoa, 
and  this  view  is  favored  by  numerous  authors  (Guarnieri,  E.  P/riJI'rr.  L.  P/cijI'rr.  Hose. 
Funk,  Councilman,  von  Wasielewski.  and  others).  Ilik-kcl  and  Horni  have  attemjjted 
to  interpret  these  structures  in  another  way. 

Negri  ("  Etiologie  der  Tollwut,"  Z./. ///yry.,  43  und  II  \^A..  l«K)3)  de.scribe>  small 
bodies  found  in  the  nervous  system  of  dogs  inoculated  subdurally  with  the  virus  of 
rabies  whicli  he  regards  as  protozoa  and  considers  to  be  the  cau.se  of  rabies.  Inves- 
tigations hy  Volpino  (/' Struttura  dei  corpi  descr.  da  Negri  nella  Kabbia."  .-1 ,  ;>t  le  Sc. 
Mrd.,y.^\n[.,  1904)  and  hy  Luzzani  ("La  dimostraz.  del  I'ara.ss.  .sju'cif.  in  un  oa.sodi 
rabljia  nel  I'uomo."  Ibid.)  .support  the  view  of  Xe,jri,  but  olTer  no  furth<-r  inforMuiln)!! 
:i<  TO  the  nature  of  the  parasite.  According  to  A.  11'.  ^Villlams,  the  .\egri  bcxlies  po.s.ses,s 
I  definite  chromidium  and  are,  therefore,  to  be  clas.sed  with    the  rhizo|)o<ls  (Journ.   uf 

lrjrrt.Dis.,m)(S).  .        ,  ,  .  •      r, 

Mallnnj  (•'  Scarlet  Fever."     Jour,  of  Med.  7?r.s.,  x..  1001)  has  f(  und  a  protozoon-hke 

I'ndv  in  four  cases  of  scarlet  fever.      Field  (Jour,>.  of  FxjHr.  Med..  1 '.)().'>)  beheves  thai 

;liese  bodies  are  products  of  <legei.eratingtissue-cellsaiulleuC(K-ytes.     Colschbrh  ("  1  roto- 

zneubefundeim  Blute  von  riecktvphuskranken."     IJ.   vud.M-ochen.srhr  ,    littU)  foun.l 

;'yar-shaped  bodies  in  six  cases  of  typhus   fever  which   resembled   the  parasites  ol 

Texas  fever,  and  in  four  cases  he  found  al>o  li.-melialed  bodies.  .  i     i-  t 

According  to  Hess  and  Guillebeau,  coccidia  may  occasion  ui  young  cattle  <li.sea.ses  oi 

intestine  resembling  dysentery.     Acconling  to  OU  and  I  ois,n,  the  slx.lty  eruption 

-wine  characterized  by  the  fonnation  of  little  cysts  in  the  skin  is  caused  l.>  cor  i. 

'  .fusrum),  but  according  to  Liilie  the.lescrii.tion  of  the  paraMt..s  do,-s  not  correspond 

to  coccidia. 

45 


706  THE    ANIMAL    PARASITES. 


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II.K.MOSPOHIDIA.  707 

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Pawlow:  Psorospermose  foUicul.   vegetante   Darier.     Areli.  f.   Derm.,  Ergiinzungslu, 

1X9.3. 
Petersen:  L^eber  die  sog.  Psorospermien  d.  Darier'schen    Kr.inkhcit.     Cbi.  f.  B.-ikl., 

xiv.,  1893. 
Pfeiffer,  E. :  Zuchtung  d.  Vaccinerregers.     C.  f.  Bakt.,  xviii.,  1,S9."). 
Pfeififer,  L,:  Die  Protozoen  als  Krankheitserreger,  Jena,    1895;    \'accinecontagiinn. 

Z.  f.  Hyg.,  23  Bd.,  1S9G. 
Salmon:  Paras,  de  la  vaccine  et  de  la  variole.     A.  de  I'Inst.  Pasteur,  1897. 
Shigami:  Vaccine-  und  Variolaerreger.     C.  f.  B..  Orig.,  xxxi.,  1902. 
Siegel:  Vaccineerreger.     Siztber.  d.  k.   Ak.  d.  Wiss.,  xxx.,  1904. 
Stroebe:  Die  parasitiiren  Sporozoen.     Cbl.  f.  allg.  Path.,  v.,  1.S94  (Lit.). 
Torok:  Die  neueren  Arbeiten  liber  Psorospermien  d.  Haut,     Monatsh.  f.  pntkt.  Derm., 

XV.,  1S92;    Paget'sche  Krankheit.     lb.,  xvi.,  1893. 
V.  Wasielewski:  Vaccineerreger.     Zeitschr.  f.  Hyg.,  38  Bd.,  1901   (Lit.). 
Wickham:  :Maladie  de  Paget  du  mamelon.     Arch,  de  m^d.  exp.,  ii.,  1N90. 
Zieler.  Paget's  Disease  of  the  Xipple.     Virch.  Arch.,  177  Bd.,  1904. 

§188.  Under  the  dcsi.uiiatiou  Plasmodium  malarife  (.Ar:irclii:if:iv:i 
and  Cell!)  or  the  haemosporidia  of  malaria  ;ii<'  .urmipcd  tojicthcr  :i(  lln- 
present  time  all  tlio.se  ])l()od  para.sites  uliicli  are  ic-arded  as  1  lie  cause  of 
human  malaria.  The  parasites  are  found  in  tliehlood  of  malarial  jjatienUs 
indifferent  forms,  usually  enclosed  in  cells;  and,  accordin.ii"  to  the  ol)- 
servations  of  Go\<j;\,  Celli,  Marchiafava,  and  otliers,  a.  ddinite  ivhitinn 
can  be  demonstrated  between  the  number  and  the  .st:i-e  of  the  (h-\eh)i.- 
ment  of  the  parasite  and  the  attacks  of  fever.  The  ])arasites  i)ass  throu^'h 
different  stages  of  development  in  the  interval  l)et\veen  tiie  attacks  ot 
fever,  these  stages,  accordingto  the  authors  mentioned,  ditVering  in /'•///•/« 
qnartcnui.  fehris  iertiana,  ami  frhris  (jit(}lidi(ni((.  At  the  snuw  t  ime  the  i>ara- 
sites  of  the  different  forms  of  fever  exhibit  certain  (bircrences  in  thnr 
phv.siological  characteri.stics.     Supported  by  tliese  fact  s,  1  hvw  ina\  t  hrre- 


7-OS 


THE    ANIxMAL    PARASITES. 


fore  be  distiiiguislied  iu  man  different  species  of  the  malarial  Plasmodium. 
Ill  its  narrower  sense  the  designation  Fkismodium  malarke  is  used  onlj^ 
with  reference  to  the  parasites  of  quartan  fever.  The  parasite  of  vernal 
tertian  on  account  of  its  active  movements  is  known  as  Flasmodium  vivux 
(Grassi  andFeletti);  and  the  parasite  of  tropical  malaria,  which  in  Italy 
ajipears  in  the  autumn,  is  designated  P/f^s»?of//»)»J»•ft'coJ■. 

Schaudinn's  classification  of  the  malarial  parasites  is  accepted  by  most  -n-riters. 
He  recognizes  three  varieties:  Plasmodium  vivax  (tertian),  Plasmodium  Tualarice  (quar- 
tan), and  Plasmodium  immaculatum  (sestivo-autumnal  parasite). 

The  development  and  increase  of  tlie  plasmodia  take  place  within 
the  red  blood-corpuscles,  in  which,  first  of  all,  small,  colorless  amoeboid 
bodies  (Fig.  539,  a)  appear.  In  quartan  frver  the  further  development 
of  the  i^arasite  proceeds  by  an  enlargement  of  the  small  amoeboid  forms 
(Fig.  539,  a,  b,  c,  d,  e),  so  that  the  red  cell  becomes  more  and  more  filled 


C; 


Fig.  t^.— Plasmodium  malarkB  of  quartan  fever,  in  different  stages  of  development.  (After  Golgi.) 
a.  Red  blood-cell  with  a  small  non-pigmented  Plasmodium  ;  h,  c,  d,  e,  pigmented  Plasmodia  of  varying 
size  inside  the  red  blood-cells ;  /,  Plasmodium  in  beginning  segmentation,  with  centrally  placed  pigment ; 
(/,  segmented  plasmodiinu ;  7i,  Plasmodium  divided  into  separate  spherules;  /,  free  gamete  (sexual 
individualL 


up  by  the  parasite.  At  the  same  time  pigment-granules  appear  within 
the  bodies  of  the  plasmodia.  When  the  i:>lasmodia  have  attained  a  cer- 
tain size,  the  pigment-granules  move  toward  the  centre,  while  at  the 
same  time  a  I'adiating  cleavage  sets  in,  so  that  daisy-like  figures 
("  rosettes  ")  (  /',  (/)  are  formed,  which  consist  of  a  pigmented  centre  and 
non-pigmented,  radiating  club-shaped  petals.  Later  the  clubs  become 
detached  from  the  central  mass  of  pigment  and  take  on  a  circular  form  (h). 

According  to  Golgi,  the  development  and  division  of  the  plasmodia  of 
quartan  fever  require  three  days  for  their  completion,  and  the  attacks  of 
fever  coincide  with  the  division  of  the  plasmodia.  The  red  cells  occu- 
X)ied  by  the  parasites  are  destroyed ;  the  young  plasmodia  just  formed 
by  division  penetrate  again  into  blood-corpuscles,  and  the  cycle  of  de- 
velopment begins  anew.  The  pigment-granules  formed  by  tlie  plasmodia 
are  taken  out  of  the  circulating  blood  loartly  fi-ee  and  partly  enclosed  in 
cells,  and  deposited  in  different  organs,  particularly  in  the  spleen,  liver, 
and  bone-marrow. 

In  febris  tertiana,  (vernal  iertlan)  the  cjcle  of  development  is  completed 
in  tM'o  days.  The  ])lasmodiai  developing  within  the  red  cells  (Fig.  540, 
a-d),  Miiich  are  designated  Plasmodinm  vieax,  show  much  livelier  motion 
and  lead  much  more  quickly  to  a  decolorization  of  the  red  blood-cor- 
puscles than  tliose  of  quartan  fever,  so  that  the  red  cells  become  decolor- 
ized on  the  first  day  after  the  fever,  while  the  plasmodia  are  still  smalL 
The  protoplasm  of  the  plasmodia  of  tertian  fever  is  also  more  delicate 
and  less  sharply  contoured  and  the  pigment-granules  are  smaller.     In  its 


MAI.AiaA.  709 

division  eacli  plasmodiuni  splits  u])  into  from  fifteen  to  twenty  n.-w  r.-lls 
(e),  while  the  parasite  of  <)naitan  fever  forms  onlv  from  six"  to  twchr. 


(-Vlli  and  Marehiafava, 

from  live  to  ten 

'■  within  a  red  eoi-- 


>pornlation  not  iiifrt-qneiitly  occnn 


According- 1 
prematnrelv 
spores  arisii 
puscle. 

The  i)arasite  of  troi)ical  or 
jyemieioKs  maJaria,  the  l*/((.stiio- 
dium  j>;u"(*o.r,  differs  from  tlie 
h?enKisporidia  of  the  vernal 
fevers,  particnlarly  in  the  fact 
that  it  is  much  smaller  (Fi<>-. 
541,  a,  b,  c,  0)  and  exeentes 
lively  movements  within  the 
red  cells.  It  completes  its  life- 
cycle  in  twenty-four  to  forty- 
eight  hours.  Through  the  for- 
mation of  a  central  vacuole  it 
often  appears  in  the  form  of  a 
ring.  During  the  stage  of  mul- 
tiplication the  parasite  collects  in  the  internal  organs,  so  tliat  the  divi- 
sion-figures ((/)  must  be  sought  in  the  spleen,  livei-,  bone-marrow,  and 
brain  (where  they  are  present  in  great  nnmliers).  Some  of  the  infected  red 
cells  become  crenated  and  prickly,  and  of  a  brassy  coloi-  (3Iarcliiafa\  a, 
Celli) ;  they  die  prematurely,  and  blood-cells  which  contain  no  parasites 
are  also  destroyed.     The  attacks  of  fever  can  in  the  case  of  autumnal 

tertian  fever  become  so  pro- 


Yia.   -AO.-PlastiXKhiim  r, 
showiiifj  different  stajfes  of  di 

((.  First  stages  of  develoj n 

withpseudopodiii:(/,  pliisiiiiMli 
Wood-cell  decolorized  ;    i .  sporiil! 
with  fliigelluiu  (luicrogainetocvtH;. 


•    of  a  viinal    teriiiin. 
'piiifiii.     iAfier(ioljj:i.) 

>,  r'.  eiiliiru''<l  phi.silloiJiu 

fores|HinilaIi tliered 

latioii ;  /,   fn-i-   piinisito 


longed    that 
one  another, 
lion     theieby 
cliaracter   of 


tliey    i)ass  into 

iukI   the   condi- 

assnines     tlie 

[I    siihroiitinuoK.s 


TTg.  .-,-tl.- 
iMwint:  iliiT' 
uifeii,-...)  , 
.ithpst 


■  f    ti 


l-rs  of  d. 


Afli 


ia  ;  c,  round  i)lasinodiiiiii  willi  piLMri 
fore  setrnientalion  ;  d,  sporulation;  c,  iiitraj-'loliular 
individual;  /,  y,  free  sexual  cells. 


or  confiiiiiinifi  frrrr. 

According  to  3Iaichiafava 
and  ("('Hi,  there  al.so  occurs 
a  quotidian  ]>arasit(;  \«'ry 
simihir  to  the  latter,  l)nt  pro- 
ducing m)  pignuMit  at  all. 

ynclc(ir  hodir.s  may  be  df- 

monstrated.  daring   certain 

stages  of  dev«'lopnient,  in  the 

prot. .plasm    of    all    the  i-ndo- 

globnlar    forms    <if    malarial 

ha'inatozoa.       According      to 

Ziemann,  in  .spornJalion  tliere  fii'st  occurs  a  (iirisiou  of  thr  r/imiiKilin  into 

.siiudl  choiips,  and  then  later  the  division  of  the  cell-body,  .so  that  every 

clump  of  chromatin  is  surrounded  by  a  zone  of  protoj.lasm. 

Besides  the  forms  of  develo])ment  already  descriln-d  wiiich  le:nl  ti>  an 
iiitrac<'llnlar  increase  of  the  plasmodia  thiongh  .sr/iizot/oiii/,  liieie  occur 
particnlaily  extraghtbnlar,  in  part  also  endoglobnlai-,  j-ound  and  o\al, 
sickle- or  crescent-shaped  .strnctures  (Fig.s.  5;;!»,  /;  ."ill,  '•../').  as  \M'1I  as 
round  bodies  with  tlagelhi  (Figs.  540,/;  541,  //),  which  also  contain  a 
nucleus  and  pigment.  The  crescent  forms  occur  ])articnlaily  in  the  ])er- 
nicious  fever  (Fig.  541,  p,  /).  Celli  regards  them  as  a  diagnostic  feature 
of  this  form  of  fever;  and  Ziemann  also  holds  that  typical  crescents  are 
not  formed  in  the  other  varieties  of  malaria. 


710 


THE    ANIMAL    PARASITES. 


The  last-named  forms  Laveran  had  already  descrilwd  as  structures 
beloiigin«i-  to  the  cycle  of  developmeut  of  the  plasmodia,  while  Gol^i, 
Caualis,  Celli,  Marchiafava,  Bignami,  Bastiaiielli,  Ziemaun,  aud  otliers 
regarded  them  as  sterile  vegetatioii-forms  that  die  Mitlioiit  further  de- 
velopment. First  through  the  investigations  of  Manson,  Bigr.ami,  Ross, 
and  MacCallum,  to  which  were  later  added  those  of  Grassi,  Bastianelli, 
Bignami,  Celli,  Laveran,  Koch,  Schaudinn,  and  others,  it  was  shown  that 
the  crescents,  the  oval  bodies,  the  spherical  bodies,  or  spheres,  as  well  as  the 
flagellated  bodies  known  as  polymitus,  are  intended  for  the  reproduction  of 
the  parasites  by  copiilaiion.  The  Hagella-ijroducing  hyaline  spheres  aris- 
ing from  the  crescents  are  male  sexual  individuals  or  microffametoci/tes, 
and  the  flagella  de^el()]>ing•  from  tliem,  in   whose  formation   the  chro- 


Fk;.  543.  Fig.  343. 

Via.  :A-^.—Aiiiii)}idcs  clavitjer.  (After  Meigen,  Zoc.  cit.)  X  4.  To  the  light  a  wing  at  higher  inii: 
uiflcation. 

Fig.  543.— Ookinete  of  hiiinau  pernicious  malaria  {Pht-vnndium  2^rcecox)  in  the  Intestinal  wall  of 
mosquito.     (After  Grassi.) 


matin  of  the  cell  takes  an  essential  part  (Sacharoff),  have  the  signiti- 
cance  of  seminal  cells,  spermatozoa,  or  microgametes ;  while  the  non-flag- 
ellated spheres  arising  from  the  granular  crescents  have  the  signiticance 
of  fem<de  sexual  cells  or  macrogametes.  The  crescents  leading  to  the  for-  , 
mation  of  the  sexual  cells  appear  only  after  the  infection  has  lasted  for  ' 
seveial  days.  In  the  chronic  cachexia  following  malaria  the  I'oinis  leaiV 
ing  to  schizogony  are  aljsent,  and  the  ci-e.scents  alone  are  present,  ; 

The  copulation  of  the  malarial  parasites  of  man  takes  place  normally  in  ^ 
the  stomach  of  the  mosquito,  in  different  species  of  Anopheles  (Fig.  542),  ; 
which  take  up  the  malarial  parasites  during  the  sucking  of  blood  fiom  ; 
malarial  ])afients.  \ 

The  copula  arising  from  the  union  of  the  macrogamete  and  micro-  ' 
gamete  is  designated  ookinete  (Schaudinn),  a  long,  motile  structure  ; 
(described  earliei-  as  vermiculus  by  Danielewsky)  which  penetrates  into 
the  stomach-wall  of  the  mosquito  ( l-'ig.  54.'>),  Avliere  tlirough  the  forma- 
tion of  a  capsule  it  becomes  the  ooci/.st.  The  latter  then  enlarges,  and  I 
forms  numerous  daughter-nuclei,  and  then  sporohlasts,  which  bre.  k  up  i 
into  the  sporozoites  (Fig.  544)  and  the  residual  body.  According  to  ' 
Grassi,  as  many  as  10,000  s])orozoites  may  be  formed  in  one  oocyst. 

The  sporozoites,  which  are  foi-med  in  enormous  numbers,  pass  into 
the  body-cavity  after  the  rupture  of  the  oocyst,  and  collect  principally  in  , 
tli«^  salivary  glands,  and  through  the  bite  of  the  infected  mosquito  are 
again  transmitted  to  man,  in  whose  blood  they  multiph'  within  the  red  . 
blood-cells  through  schizogony. 


.MAI.AIUA.  711 

The  palhof/nu'c  sif/iiificaiwe  of  iJir  walai'ial  yhixiuoilia  rosN  in  IIh'  iii-st 
phu'C  upon  llu' dostiiu'tiou  of  ivd  blood-cells.  Jii  tlio  pernicious  form 
this  may  be  so  extensive  tlmt  li;enio.iilobiniiri:i  may  lake  place.  The 
melanotic  pijAHi*^"!'!  formed  in  the  paiasile  is  a  ])ro(lMct  of  the  ^ital  ac- 
tivity of  the  parasites.  In  atldition,  as  the  Jesuit  of  t he  destiuctiou  of 
luemoglobiu,  there  occur  deposits  of  hojmosiderin  in  the  bone-marrow, 
sjileen,  liver,  and  occasionally  also  in  the  kidneys.  Jn  the  ease  of  u 
marked  destruction  of  the  I'cd  blood-cells  there  may  occur  an  excri'liuu 
of  dark  red  urine,  a  htemo<ilobinuria  {hhicl-irairr  fever).  The  massing;  of 
the  parasites  of  peiiiieious  malaria  in  the  cerebral  capillaries  may  cau>se 
circulatory  distuibances  Mith  the  occurrence  of  numerons  ha'm(trrhaj;;es, 
andeonseipu'iit  severe  ci'rebral  symptoms  (perniciosiicomalosa,  Boporos;i, 
apo])leet  iea,  meningitica). 

As  the  result  of  the  retention  of  piji;ment-coutaininji  malaiial  i)arasites 
and  the  dei>osit    of  the   ])r()ducts  of  blood-destructiiui,  thei'e  oceui's  a 

marked  swellin*;"  of  the  spleen  associ- 

--^■^"•^'^^''~^5?«i  '^^*'^^  with  hypera'mia,  followed  in  i)ai't 

y-^V-T'iN^^y'^^'C"^^  bv  tissue-deu'enei-atioiis  and  in  i)art  bv 

.-^^V,^?.  #^;V','^\  tissue-proliferations. 

A\4V'  •'  ^  'S        '^'  ^W^"v\  Altera  Ion-- dniat  ion  of  1  he  process 

/5^'^;ill/      '^      /;'■>>' "■''^^  the  spleen   may  become   markedly   en- 

^ ''c^%^^^' "■' A-     ,^"i'-:^    "^^^    ^^        larg'ed,  pi^inented,  andjii-eatly  chanj;-ed 

/^l -->^*^ \":\^^  \^4>^^^''>   v"N^^        iu    structure.     Liki'wise,    in    the   liver 


I  v^^i'>«^i\l^ML''''^'W  '  .>   '  there  may  be  found  in  i)art   (le,u-enera- 

tions  and  i)ijinientati(ms,   and    in    part 
also  indurati\('  ])rolifeiations. 

Certain  rarietir.s  of  tlie  j>li(siiiiftlli(ni 
correspond  to  the  iiidi\idnal  types  of 
fexei',  as  .<;i\«'n  abox c,  but  it  must  be 
noted  that  the  fever-forms  known  as 
([uotidian,  subcontinuous,  and  continu- 
ous ('v'o»*/^f/f("),  may  also  arista  thr<»u<;;li 
the  i)resence  iu  the  blood  of  dideient 
generations  of  the  pinsmodia  of  tei-tian 
or  <piartan  feveis,  so  that  daily  a  jxtrtion  of  the  ]>arasites  comes  to  sporu- 
lation.  In  this  way  there  arise  (piotidian  forms  of  fe\er,  which  n:nst  Ini 
legarded  as  a  double  tertian  infection  or  as  a  tiiple  rpiartan. 

According  to  the  investigations  by  .Schaudinn,  the  nhipaea  that  occur 
sometimes  weeks  and  months  after  the  original  attack  may  be  e\plaine<l 
by  the  fact  that  the  macrogametes,  which  are  longer-li\-ed.  re\«'rt  to 
schizonts  by  throwing  off  a.  portion  of  their  nucleus  and  i)rotoplasm. 
According  to  Plehn,  basoi)hile  granules  are  found  in  the  red  blood-cells  as 
loug  as  the  infection  persists.  They  vanish  when  the  infection  linally 
comes  to  an  end. 

The  malaria  occurring  in  norlhein  countries  conesponds  in  general 
to  the  vernal  forms  of  Italy,  while  the  a'sti\ o  aiil  uninal  form  i-  found  iu 
the  tropics. 

Haemosporidia — tliat  is,  sporozoa  xvliicli  livo  at.  f  lie  cost  ol  ilio  red  iilood-cflls,  iiiid 
tli(Mcl)V  produce  diseases  which  are  to  be  classed  v.ilh  malaria— occur  very  frec|iieMtly 
in  animals.  Those  of  birds  are  best  known  (Dunilcwski/,  MacCdllutn,  kuss,  (iraMni, 
Dionini,  Cclli,  and  Schaulinu)  and  the  life-cycles  of  the  ha>ni()sporidia  C)f  the  piKoon, 
owl,  and  skylark  have  been  deterniined.  Lablx'  distinKiii-^lif-^  <\\f>  fienera  in  birds,  //«/- 
teridium  and  Proteosoma  (IlwrnoprolenFs  of  Knise);  as  to  the  number  of  nniiilTerentiate<l 
siJecies,  nothing  can  be  said  at  the  present  time.     CilU  obtained  from  the  l)irds  men- 


712  THE    ANIMAL    PARASITES. 

tioned  three  well-dofined  species.  Schaudinn  assigns  the  parasites  of  birds  designated 
as  proteosoma  to  the  genus  plasmodium. 

Of  the  Mammalia,  cattle  in  particular  suffer  indifferent  countries  (Southern  States 
of  North  America,  Italy,  South  Africa,  Roumania)  from  a  malaria  characterized  by- 
high  fever  and  hsemoglobinuria.  In  the  malaria  of  cattle  known  as  Texas-fever,  Smith 
and  Kilbourne  foimd  in  the  red  blood-cells  a  small,  often  pear-shaped,  and  paired  parasite 
{Piroplasma  bigeminum),  whose  pathogenic  significance  they  determined  through  the  in- 
oculation of  healthy  cattle  with  blood  containing  the  parasites.  Babes  foiuid  the  same 
parasite  in  the  epidemic  haemoglobinuria  of  cattle  prevalent  in  Roumania.  The  first- 
named  observers  showed  further  that  the  natural  infection  takes  place  through  parasitic 
ticks  {Bodp}tilus  bort's)  livingupon  the  cattle,  the  infection  being  transmitted,  not  by  the 
same  tick  which  takes  up  the  infected  blood,  but  only  through  the  generation  descend- 
ing from  the  same.  This  mode  of  infection  was  confirmed  by  Koch  in  the  hannoglobin- 
uria  of  cattle  occurring  in  German  East  Africa  and  by  Grassi  in  that  occurring  in  cattle 
in  Italy.  The  mode  of  development  of  the  piroplasma  in  the  body  of  the  tick  is  still 
unknown;  and  it  therefore  cannot  be  decided  whether  the  parasite  should  be  classed 
with  the  known  malaria  parasites.  Against  a  near  relationship  with  the  latter  speaks 
the  fact  (Liihe)  that  it  increases  within  the  red  blood-cells  by  a  repeated  simple  d'vision. 
According  to  Kolle,  there  occurs  in  South  Africa,  besides  Texas-fever,  another  malarial 
disease  of  cattle  {Fcbris  malariaformis),  which  is  caused  by  an  endoglobular  parasite. 
Theiler  also  distinguishes  two  forms  of  piroplasmosis  of  cattle  in  South  Africa.  The 
piroplasma  occurring  in  dogs  and  in  horses  he  regards  as  an  especial  form  distinct  from 
Piroplasma  bigeminum.  According  to  observations  by  Nocard  and  Almy  and  Motaf 
a  piroplasmosis  associated  with  hpemoglobinuria  is  not  uncommon  in  dogs  in  France. 
According  to  Galli,  Valerio,  and  Piana,  it  occurs  also  in  Italy. 

According  to  Bonome  and  Celli,  hsemosporidia  also  cause  malaria  in  sheep  and  lamb:,, 
according  to  Koch  and  Kossel  also  in  apes,  and  according  to  Dionisi  in  bats;  but  the 
life-history  of  all  these  parasites  is  unknown. 

Ban  lie  irdy  and  Celli  have  described  lifemosporidia  in  the  frog,  and  the  latter  ob- 
server deteimined  also  the  development  of  the  parasite  in  the  blood. 

Whether  the  malarial  parasites  of  man  can  be  transmitted  to  animals,  or  whether 
the  malaria  of  animals  can  lead  to  an  infection  of  man  through  the  medium  of  mos- 
quitos,  is  not  decided  with  certainty,  but  appears  improbable.  The  plasmodia  of  the 
bat  most  closely  resemble  those  of  man,  yet  attempts  at  inoculation  made  by  Bionid 
gave  no  positive  results.  It  may  therefore  be  assumed  that  malaria  would  die  out  iu 
a  given  region,  either  when  all  susceptible  anopheles  were  killed,  or  all  infected  human 
individuals  healed  or  protected  from  mosquito  bites. 

The  malarial  plasmodia  are  stained  best  by  the  Romanowski  stain,  which  differen- 
tiates the  nucleus. 

The  view  that  mosquitos  were  concerned  in  the  distribution  of  malaria  is  very 
old,  and  hasobtainedin  Italy  siuc-e  Roman  times.  Km-Jt  found  it  held  as  a  popular  belief 
also  among  negroes.  In  recent  times  Jfn^snti  (ls!»(;)  and  /.'/////(o/// (189(5)  were  the  tirst 
to  turn  their  attention  to  the  problem  and  to  give  liyi)()tiieses(((ncerning  tlierole  i)layed 
by  mosquitos  in  the  spread  of  malaria.  Bi;/iiiitiii  carrk'd  out  experiments  along  this 
line,  but  came  to  no  positive  result.  Boss  was  the  first  (1897-98)  to  determine  the  cycle 
of  development  of  the  malarial  plasmodium  of  birds  (usually  known  as  in'oteosoma). 
According  to  his  investigations,  the  parasites  taken  uji  with  the  blood  of  the  infected 
bird  into  the  intestinal  canal  of  mosquitos  penetrate  into  the  intestinal  wall  and  there 
change  into  cj'sts  in  which  innumerable  lod-sliaped  germs  develop.  Becoming  free, 
these  germs  gain  entrance  into  the  saliva) y  glands  of  the  mosquitos,  and  thence  into 
the  organism  of  the  bird  dnring  the  act  of  blood-sucking.  Ross  found  the  parasites  iu 
the  blood  of  the  infected  bird  in  from  live  to  nine  days  after  the  infection. 

About  the  same  time,  Grassi  found  through  painstaking  observations  that  the  dis- 
tribution of  malaria  in  man  corresponded  to  the  distribution  of  Aiwphcks  claviger 
{Fahricius)  (Fig.  542),  and  not  to  that  of  the  conunon  mosquito  {Culc.v pipiens).  Basing 
his  experiments  upon  this  observation,  Bigndini  succeeded  in  producing  malaria  iu 
healthy  men  by  means  of  tiie  bite  of  anopheles.  Later  Grassi,  in  cooperation  with 
Bastiaiielli  and  Biuiuinri,  succeeded  in  determining  the  life-cycle  of  the  malarial  par- 
asite  It  w'as  then  shown  that  several  species  of  anopheles  native  in  Italy  {Anopheles 
claviger  [Fahrici II s^  or  Anopheles  viaculipennis  [Mei'gen],  Anopheles  sriperpictris,  psevdo- 
jnctus,  bif II  red  tils)  s])read  the  malaria  occurring  in  man,  while  Vulex  pipiens  is  tlie  host 
of  the  parasites  of  bird-malaria 

The  cycle  of  development  of  the  malaria  plasmodium  is  as  follows:  "Within  the 
blood  (of  man  as  well  as  of  birds)  the  nnillipiicatioii  lakes  jilacetirst  hy  schixorjony.  The 
young  form  of  the  plasmodia,  represented  by  a  small,  unpigmented  body,  grows  within 
the  red  cells  (Fig.  545, 1)  into  a  larger  body    (i^),  iu  whose  central  portiou  pigment- 


ii.KMospoinniA. 


'i:i 


granules  collect.  This  ccll-body  known  as  srl,iz.n,t  shows  in  preparation  for  8chi/oir..nv 
an  increase  ol  nucK'i  (.;),  and  then  divides  into  a  nunil.cr  (vaVvin-  will  •  "">"">. 
*/)o;vs  or /«(7v/.^f><^(.v(^)\vitii  tlie  abandonment     ■"        '  -•-■-' 

zoites  tlien  secJi  a  red  bh 


tlie  species)  I 
ly.     Tile  nier 


,,  't  a  pigmented  residual  b( 

'I  (/).  and  tlie  cycle  is  ay:ain  beirun. 
_  In  .porononij  the  nierozo.tes  develop  into  s.'.xual  individnals.  nmcnwimctcs  (.-7)  and 
microgametocytes  (.y)  ^M.en  taken  up  into  the  stoma.!,  bv  bhuul-suckini  ,m  s- 
T^i  %^T'f  ^"^^'^■'^^"fl^  i?^^''"'^'  ^iP^  f'"-  fcrtiii/ation.  U.,.  mac-roiramitc  bv 
throwmgoff  thckaryosome(^;)  themicrogumctocyle  through  th.-  for,„ati..n  of  micro- 
game  cs  (u<,)  Copulation  then  fol  o^ys  (?).  From  the  copula  arises  ti...  m.-lile  o.Uin.-t<. 
{^),  ^vhlch  in  the  wall  of  the  mosquito's  intestine  becomes  the  oiuvst.  in  whi,!,  tliro  Jh 
the  division  ot  the  nucleus  the  sporoblasts  (U)  -aw  formed,  which*  in  turn  break  u.)  int 
a  large  numb(.r  of  sporo/.oites  (70)  which  (//).  becoming  free,  collect  chieflv  in  the  sali- 
vary  glands,  and  are  thence  transferred  l,y  the  bite  of  tlie  mos.juilo  to  a  now  host  in 
whose  blood  they  increase 
through  schizogony  (1-4). 

According  to  the  inves- 
tigations of  Schauclinn,  the 
macrogametes  and  the  micro- 
gametocytes  of  Plosmodiuui 
i'ivax  may  be  distinguished 
from  each  other  in  the  earli- 
est stages  of  development 
within  the  red  blood-cell, 
and  also  from  the  schizonts, 
at  first  througli  the  peculiar 
structure  of  the  nucleus  and 
later  through  that  of  the 
protoplasm.  In  a  new  in- 
fection of  tertian  malaria  the 
differentiation  of  the  gametes 
began  after  the  third  attack. 
The  growth  takes  place  es- 
.sentially  slower  tlian  in  the 
case  of  the  schizonts.  The 
pigment  production  is  more 
ainmdant,  while  the  nucleus 
is  larger  and  less  dense. 

The  larva^  of  anopheles 
live  chiefly  in  slowly  flowing 
water.  The  eggs  of  Anoph- 
eles claviger  retjuire  about 
thirty  days  at  20-25°  C.  for 
the  development  of  the  in- 
sects, and  these  in  turn  lay 
eggs  when  twenty  days  old. 
The  pup;e  are  resistant  to 
drying,  to  cold,  and  to  con- 
tamination of  the  water. 
The  mos'piitos  fly  during  the  evening  and  night,  but  do  not  rise  very  high  above  the 
level  of  the  earth,  and  do  not  go  very  far  away  from  the  place  of  development.  Ac- 
cording to  Grassi,  Bignnmi.  and  Bastianelli,  the  a'stivo-autumnal  parasites  will  not 
develop  in  anopheles  at  a  temperature  of  14-15'  ('.,  and  grow  only  slowly  at  20  20 
C;  at  30  V.  they  complete  their  entire  developnienl  up  to  tlie  "formation  of  sporo- 
zoites  in  about  .seven  days. 

The  literature  concerning  malarial  parasites  is  extremely  rich.  The  results  of  the 
latest  investigations  are  given  in  the  publications  of  Grassi,  Schuwtinn,  Munnabcnj, 
Nvitall,  Celli,  Marchiafava.  Bignami,  and  Liihe. 


Fig.  54.5.— Cycle  of  develdpiiu'iit  of  Pruti  osunm.  iMwv  Scliau- 
dinn  and  LUhe.)  1,  Sporozoile  (or  iiitTozuitc)  wiiliiii  u  n-d  1)|ikkI- 
eorpuscle;  2,  schizont;  S,  scliizont  witli  nuineri)iis  miclcl ;  /..  wlilz- 
og-ony,  formation  of  merozoitcs ;  .",  iiia(To(raiii''lt'  (ft'iiialf  r«>ll) 
arisitifr  from  a  merozoite ;  ';,  fully  devcloiicd  riiacn>L'anict<'  aftrr  v\- 
tiusiiiti  of  the  kiiryosoiiie ;  .''/,  inicniiriiiin'iDcvtc  (inalf  (••■11)  arlsliiir 
fmiii  a  merozoite;  6V(,  niicriiiraiiiftiH-vti-  Mirnpimdcd  hy  I'wxw'iifil 
iiiiiTotrametes  (spermatozoa)  ;  7.  fertilization  of  Hit'  iiiarnvaiiii'tc; 
•V,  ookinete;  .9,  oocysts  with  sporol)lasts  ;  /",  oipcvsUs  wlili  sixirozolifs; 
1 U  free  sporozoite. 


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I 


INI  rsoHiA. 


71; 


xix.,  1N9." 


|NM<.»: 


:((Mir.  isnn. 

•.    l'.-,>t<Mir 


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I'eber  Malaria  und  andere  Blut]iarasiten,  Jena,  189S. 

§  ISO.  Of  the  ciliates  or  infusoria  occnrriii<i"\vi11iin  Hk'  1iiiiii:iii  ui-aii- 
ism  llir  best  known  and  most  important  is  the  Balantidium  ^>v  Para- 
tnascium  coli,  a  nnicellnlar  anijual  60-70  />.  loiij;',  cox  ♦•red  \\itli  slmrt  imi- 
form  cilia.  At  its  anterior  end  it  Las  a  short  ])eristoma  (Fi-.  ."■>}(),  a) 
which  opens  into  a  short  gnllet.  The  body  is  maiked 
with   i)urallel    stri]ies    and    encloses    a    bean-sli;i|)ed  ;  ^ 

chief  nuclens  (/>)  and  an  accessory  nncleiis  iind  two 
vacuoles.  Multiplication  takes  i)lace  by  <li\isi<)ii 
into  two  new  indi^■idnals.      It  develops  a  ])ermaMent      |>?',  ^^ 

form  ill    the   shape   of  a  spherical  cyst  witli  a  linn      f'"  ' 
membrane. 

Balantidium  call  occurs  Aci-y  often  in  the  c(d<iii  "i 
swine  without  causint;  a]>iiar«'iit  chaiif;-es.  In  cases  oi 
dironic  diarrhtea  in  man  it  lias  been  found  in  tlie  (h-- 
jections  and  in  the  C(»h)n,  and  prol)ably  stands  in 
causal  relation  to  the  intestinal  catarili.     Accnnlini;  .        '' 

to  in\-esti,i;ations  l)y  H<)lowjew,  Askana/.y,  Klinienko, 
and  otlu'rs  tlie  balantidia  may  ])en<'trate  into  the  mu- 
cosa and  sn])muco.sa  of  the  intestine  and  caus(^  there 
ulcer.s.     Tliey  may  also  wander  into  the  blood- ves.sels. 


Klli.      ■•\<:       IS.II.IIlliil- 

iuin  {tHjniinivriHiii} 
(■<(//,  with  two  roiiinn-- 
tlli-  vaciioli-s.  (AftiT 
Cliiiis.)  II,  Mouth:  />. 
niiflciis;  r.  liH-luilfil 
stanli  tfniliiM:  </,  for- 
i'\lit\  ImmIv  in  Ihf  iirt  of 
IH-Intr  extniihMl.  Illtrli 
iiiatrnilU'iitloii. 


Other  species  of  ciliates  have  been  observed  in  the  infest im 
of  man,  Balantirlhnn  minutnm  {Schaudinn,  1899)  and  Xi/I.l»- 
therus  /aha  (Srliantlimi).  In  the  jjaiinch  and  reticulum  of  rumi- 
nants, in  which  the  cellulose  digestion  is  carried  on,  and   in  the 

blind  intestine  of  horses,  infusoria  are  universally  present  an<l  occur  in  enorinoiu 
numbers,  for  example,  Isotricha  prostoma.  Entodinium  caudal iim.Ophnfosrolrx  amdntus 
and  othei-s. 


716  THE    ANi:\IAL    PARASITES.  , 

(Cilkdcs.) 

Askanazy;  Pathofr.  Bedeutung  d.  Balantidium  coli.     Verh.  d.  D.  path.  Ges.,  v.,  1903. 
Cohnheim:  Infusorien  im  Mageii  und  Darm.     D.  med.  Woch.,  1903. 
Doflein:  Die  Protozoeii  als  Parasiten  und  Kraiikheitserreger,  Jena,  1901. 
Eberlein:  Jnfusorieu  im  Wiederkauermagen  (komnien  normal  vor).     Cbl.  f.   Bakt., 

XX.,  1896. 
Grassi:  Protistes  endoparasites.     Arch.  ital.  de  Biol.,  ii.  u.  iii.,  1SS2-S3. 
Grimm:  Leberabscess und Lmigenabscessmit  Infusorien.     LangenbecksA.,48Bd.,  1894. 
Hansen:  Infusorien  im  Magen  bei  Carcin.  ventriculi.     D.  A.  f.  klin.  Med.,  59  Bd.,  1898. 
Jakoby  u.  Schaudinn:  Xeue  Infusorien  im  Darm.     Cbl.  f.  Bakt.,  xxv.,   1899. 
Janowski:  Balantidium  coli  im  Stuhl.     lb.,  32  Bd.,  1897  (Lit.). 
Klimenko:   Z.  Pathologic  d.  Balantidium  coli.     Beitr.  v.  Ziegler,  xxxiii.,  1903. 
Lang:    Protozo;i,  Jena,  1901. 

Malmsten:   Ueber  Balantidium  coh.     Virch.  Arch.,  12  Bd.,  1857. 
Molter:   Zur  Kenntnis  des  Balantidium  coli.     I.-D.,  Kiel,  1891. 
Solowjew:  Balantidium  coli  als  Erreger  chron.  Durchfalle.     Cbl.  f.  Bakt.,  xxix.,  1901 

(Lit.). 
Stieda:  Ueber  Balantidium.     Virch.  Arch.,  55  Bd.,  1896. 

Strong:  The  Clinical  and  Pathological  Significance  of  Balantidium  Coli,  Manila,  1904. 
Strong  and  Musgrave:  Infect,   with  Balantidium.     Bull,   of  Johns  Hopkins  Hosp., 

xh.,  1901. 

H.  Vermes  (Worms). 

A.  Platyhelminthes  (Flat-AVorms.) 
1.   Treynatoda,  Sucking   Worms. 

§  190.  The  Trematodes  or  sucMng- worms  are  flat- worms  of  tongue  or 
leaf  shape.  They  possess  a  clinging  apparatus  in  the  form  of  ventral 
sucking-cups  of  varying  number,  and  are  sometimes  furnished  with  hooks 
or  clasp-like  horny  projections.  The  intestinal  canal  is  without  an  anus, 
and  is  usually  forked.  The  development  takes  place  either  by  the  direct 
growth  to  maturity  of  the  embryos  {miracidlum)  hatching  from  the  eggs, 
or  by  tlie  method  of  alternate  generation  thiongh  the  fonnation  of  germs 
within  the  host.  The  miracidium,  or  ciliated  embryo,  penetrates  into  a 
snail  or  mussel,  and  there  grows  into  a  germ-sac  {sporocyst),  within  which 
there  later  develops,  either  directly  or  after  the  formation  of  an  inter- 
mediate generation  of  germ-sacs  {redice),  a  swarming  generation  of  cer- 
carice,  which  are  provided  with  rudder-like  tails.  These  lose  their  tails 
and  penetrate  into  a  new  host  (mollusks,  arthropods,  fish,  amphibia), 
become  encapsulated,  and  attain  sexual  maturity  as  soon  as  they  reach 
the  final  host.  The  germ-sacs  which  produce  cercarite  are  designated 
primary  germ-sacs  ("^4w,we?i")  ;  if  they  first  form  rediie  and  then  cer- 
carise,  they  are  called  secondaiy  germ-sacs  (^'  Grossammen^'). 

Distoma  hepaticum,  or  liver-fluke,  is  a  leaf-shaped  sucking-worm 
about  2.S  mm.  long  and  12  mm.  broad  (Fig.  547).  The  cephalic  end 
projects  like  a  beak,  and  bears  a  small  sncking-cup,  in  which  the  mouth 
is  placed.  Close  behind  this,  on  the  ventral  surface,  is  a  second  sucking- 
cup,  and  between  the  two  lies  the  sexual  orifice. 

The  uterus  consists  of  a  convoluted,  globular  sac  behind  the  posterior 
sucking-cup.  On  each  side  of  the  hinder  part  of  the  body  lie  the  yolk- 
sacs,  and  between  the  same  are  found  the  testicular  canals,  which  branch 
many  times.  Tlie  forked  intestinal  tract  (not  visible  in  Fig.  547)  is 
repeatedly  branched. 

The  eggs  (Fig.  54S)  are  oval,  0.1.3  mm.  long  and  0.08  mm.  broad.  In 
water  there  deveh)ps  nn  embrvo,  the  miracidinm   (Fig.    549,    A),  with 


THK.MAI'ODA. 


717 


(•ellular  i;erni-balls  (a) ;  witli  tlio  aid  ol"  its  ciliat*'!!  c<)v<'iiii<;-  llic  i'liiliryo 
swims  about,  and  seeks  out  ;i  new  liost  lioin  the  laiiiily  of  niollnsks 
{Limncvioi  miimtus).  On  penetration  into  the  snail  the  eutaiH'oiis  hiyer  is 
thrown  off,  and  the  mina-idiion,  whieh  jxjsscssc's  an  intestine,  an  excre- 
tion-oro-an  and  a  brain-«;anolion,  beeonu's  chaiiiicd  \n\o  u  .spnrorj/Mt  (li), 
in  whieli  tlie  intestine  and  nervous  system  atrophy,  whih- t hi' ecMnhir 
germ-balls  develop  further  {Ji,  ^0  anil  t'oiin  ;i  f«co,ul  f/r,i,nilinii  off/mn- 
A«('.s,  the  r('(liw(Ii,  b).  The  redia- (r)j  which 
possess  an  intestine  ((',  a),  i»rudnct'  then 
within  the  same  host  the  ccrcar'nv  (/>)  fioiii 
cells  Avhieh  are  loosened  ii<»m  tiu-ir  j^cnu- 
nmtrix  (r,  h);  tlu-sr  abandon  the  host  siiul 
with  the  aid  of  a  rud(h'i-likr  tail  swim  about 
in  the  water.  AVith  the  loss  of  their  tails  they 
become  encysted  upon  almost  any  foreij^^'n 
body,  and  then  reach  tlu'ir  iinal  host  (nsnally 
throuo-h  the  food),  in  Mhich  they  attain  s«'X- 
ual  matuiity.  Tiie  sexnally  mat  me  animal 
inhabits  the  biliary  i)assa«;es;  more  larely  it 
is  found  in  the  intestine  or  inferior  vena 
cava.  The  liver-fluke  is  rare  in  man,  but 
common  in  cattle  and  sheep.  The  results  of  its 
invasion,  es])ecial]y  when  it  is  ])i-esent  in 
gieat  numbers,  are  obstrnction  and  nicer-alive 
strictures  of  the  bile-passa<i-es,  formation  of 
biliaiv  concretions,  iuHammation    of  th<'  tis- 


Fig.  '>i7. —Distonin  hfpaticiim  with 
Fk;.  .548.— Egffs  of  Distoma  lit-paticuii 


u'Xiial  a|ipaniliis.     (AfliT  Lfiickart. 


sues  in  the  neighborhood  of  the  bile-ducts,  and  hyperplasia  of  I  lie  peri- 
l)ortal  connective  tissue  of  the  liver  with  atio])hy  of  the  glamlnlai-  tissue. 
The  same  changes  ai«^  found  in  cattle.  In  shee)»,  following  a  marked  in- 
vasion of  lh(;  liver,  there  may  develop  a  gener-al  cachexia. 

Distoma  lanceolatum  is  oidy  8-9  mm.  long  arrd  2-2.")  mm.  broad,  is 
lancet-shaped,  and  the  cephalic  portion  is  irot  especially  rrrarked  ofl' 
from  the  body  (Fig.  ."iSO). 

The  skin  of  the  body  is  .smooth.  Two  ii  rvgrrlarly  h.lu-d  testicles  (//) 
lie  close  behind  the  vent i-al  srrcking-cnp,  irr  front  of  the  ovary  (o)  and 
the  uterus  (»),  the  coils  of  Avhich  shirre  throrrgh  the  t rarrspai«'nt  body. 
The  anterior  coils  are  black  Avith  the  ripe  eggs,  the  others  arv  nrsty  red. 
The  yellowish-white  yolk-sacs  (^0  lie  in  the  nriddle  of  lire  later-al 
margin. 

The  oval  eggs  are  0.04  mm.  long,  and  while  still  in  the  nlenrs  contain 
an  embryo  which  escapes  only  after  several  weeks  following  Ihe  casling- 
off  of  the  eggs.     Its  metamoiphoses  nr-c-  rrnkirowrr. 

Distoma  lanceolatrrm  likewise  iidiabils  the  bile-j.assages,  i>rrt  is  vei-y 


718 


THE    ANIMAL.   PARASITES. 


rare  in  man.  11  is  of  more  frequent  occurrence  in  sslieep  and  cat  tic 
\Vhen  present  only  in  small  numbers,  it  causes  no  marked  changes;  but 
the  presence  of  large  numbers  may  excite  inflammation  and  proliferation 
of  the  periportal  connective  tissue. 


c^m     x^^^:;^^ 


Fig  549 —Development  of  the  liver-fluke.  (After  Leuckart.)  ,4.,  Miiacidium  with  germ-balls  (a) :  i», 
sporocyst  with  genn-balls  (a)  and  rediffi  (/>)  ;  C.  redia,  with  intestine  (a)  and  germ-balls  (b) ;  D,  cercaria 
with  mouth  (a),  abdominal  sucking-cup  (t>),  intestine  (f ),  and  glands  (d). 


Distoma  spathulatum  (Fig.  551)  is  a  sucking- worm  occurring  in 
man  in  Japan  and  China.  It  is  10-14  mm.  long  and  2.5-4  mm.  broad. 
The  eggs  are  0.027-0.03  mm.  long  and  0,015-0.01  s 
mm.  broad.  The  parasite  inhabits  usually  the  bile 
passages  and  the  gall-bladder,  but  may  also  gain 
access  to  the  pancreatic  duct  (Katsiu^ada),  and  pas> 
out  into  the  intestine.  When  occurring  in  great 
numbers  (Katsurada  counted  4,361  in  one  case)  it 
causes  an  obstruction  to  the  outflow  of  the  bile,  and 
often  excites  a  more  or  less  severe  inflammation  and 
proliferation  of  connective  tissue. 

The  parasite  is  found  also  in  cats  and  dogs 
(Katsurada). 

Distoma  Westermanni  (Kerbert),  or  Bistoma 
pulmonale  (Baelz)  also  occurs  in  Japan,  China,  and 
Corea.  The  worm  is  7.5-10  mm.  long,  5-7.5  mm. 
broad,  egg-shaped,  with  slightly  flattened  ventral 
surface.  The  oval  eggs  are  0.09  mm.  long  and 
0.056  mm.  broad.  The  internal  organization  (Fig. 
552)  resembles  that  of  the  other  t  rem  at  odes.  It 
occurs  in  man  as  well  as  in  cats  and  dogs  (Katsu- 
rada). It  is  found  most  frequently  in  the  lungs, 
but  occurs  also  in  other  organs:  the  jjleura,  brain, 
liver,  intestinal  wall,  peritoneum,  orbital  cavity, 
eyelid,  scrotum,  etc.  In  each  case  it  occuiiies 
small  cavities  surrounded  by  newly  formed  con- 
nective tissue,  and  occurs  occasionally  in  pairs.  In 
the  lung  it  may  be  found  also  in  the  bronchi,  the 
walls  of  which  show  inflammatory  changes  (Katsu- 
rada). Its  presence  in  the  lung  may  give  rise  to 
hfemoptoe  and  cause  death.     The  number  of  luug- 


FiG.  riTiO—BistDma  \an- 
ceolatum.  (After  llcrtwig.) 
«i,  Anterior  surkiiiLM-up. 
and  entrance  into  I  lie  fiirkcd 
intestine;  s",  post  er  i  or 
sucking-cup;  /(,  testicles 
with  vasa  deferentia;  c, 
cirrus;  ?(,  uterus;  n,  ovary; 
I,  duct  of  Laurer  and  she'll- 
Kland;  d,  yolk-stalks  and 
duct  leading  to  the  shell- 
gland  ;  w,  water-vessel ;  p, 
ganglion,    x  s. 


DiSTOMA. 


71<* 


flukes  may  I'uu  from  tweniylo  lliiily  or  cxcn  Iii^ln-r.  HimIIhix  nf  tlir 
disease  is  possible  after  death  of  the  i)arasit»'. 

Distoma  felineum  (Hivolta)  or  Distoma  .sihiririiiii  (Wiiio<,M:ulo\v)  is  a. 
flat,  almost  transparent  suekiiij;-\vorin,  of  from  S- 10  mm.  in  h'n^tli  and 
1.5-2.5  mm.  broad,  Miiieli  is  present  in  the  bilo-i)assa^«'S  of  tlu'  eat  and 
dog",  and  in  a  few  eonntries  (SiluMia)  has  been  obst-rxed  in  man.  .\c- 
cording-  to  "Winogradow  it  is  tlu'  most  eonunon  i>arasitc  in  Tomsk. 
Askana/.y  roeently  observed  several  eases  in  KiniijislxT^.  'flit'  sumkcs 
of  the  infeetion  were  tish  eaten  raw  (roaeh,  Lcm-i.srii.s  nill/ii.s). 

The  inflammatory  proliferations  whieh  tlu^  dillVrcnt  forms  of  distoma 
cause  in  the  liver  of  man,  as  well  as  in  animals,  may  bo  lollowrd  l)y  the 
development  of  eareinoma. 

In  Distoma  haematobium  ov  BiUiarzia  ha'iii(ttohi((  {Vh^.  TtX',)  i lie  two 
sexes  are  sei)arate.  The  mouth  and  ventral  eni)s  lie  very  eloso  lom-thor 
ou  the  tapering-  anterior  extremity.  Jn  both  se\<'s  t lie  sexnal  openings 
lie  close  behind  the  veutral  sucking-eup.     The  male  is  I.!   1  I  mm.  long. 


a 


Fifi.  'i-'A.—DtMDma  npntliulatiui 
d,  testicles;  e,  yolk-stalks;  /,  speiiii-i 

Fig.  5^2.— Distoina  ^V 
a,  a„  Mouth  and  abduiniii 
yolk-stalks;  /,  slK'll-<.'lan.l : 


(Aft<T  Katsiirada.)    <i,  Mniiili  «*ii.'kii 
uch  ;  (/.ovarium.    '/  0. 
trriDdinii.  Ilatiened  by  prfssuri'.  in  tlic  vcntnd 
suckin}r-cup  respectively;  '»,  inK^^stlnal  limps; 
[/,  uterus;  li,  excretory  vessel.      ■   7.:i. 


ir-iiip:    /i,  Inl.-stliu 


iwisitiiin.     (Afier  Kul.suniilu. 
c,  Ifstldes;  W.    oviirluiii;   i 


The  body  is  flat,  bnt  in  its  posterior  i»oitioii  is  r(.ile<l   togelh<-r  to  1.. 
tube  (Fig.  553)  whieh  serves  for  the  reception  of  tlie  female. 

The  female  is  1(3-10  mm.  long  and  nearly  eyiindrieal.  The  egg; 
an  elongated  oval  (Fig.  554),  0.12  mm.  long,  and  pi.ssess  ;i  termuu 
a  lateral  spiue.  Accoi-ding  to  observations  by  Sonsino.  no  :dtein:iti. 
genei-ations   occurs   in    the  development   of  IHsUma  hwmutohnnn. 


.  are 

il  or 

11   ol 
Ihr 


720  THE    ANIMAL    PARASITES. 

part  of  intenuediate  host  is  taken  by  small  Crustacea,  into  wiiicli  the 
ciliated  eiubi  yo,  swinimiug  around  in  water,  bores  its  way  to  become 
encapsulated  in  the  tissues  of  its  host.  It  is  therefore  probable  that  the 
infection  may  be  transmitted  through  the  drinking  of  water  infected 
with  the  larvtie. 

The  worms  are  found  in  the  trunk  and  branches  of  the  portal  vein,  in 
the  splenic  vein,  mesenteric  veins,  as  well  as  in  the  vessels  of  the  rectum 
and  bladder ;  and  may  pass  through  the  inferior  mesenteric  vein  into  the 
hsemoi-rhoidal  and  vesical  veins,  the  veins  of  the  ureter  and  j^rostate, 
and  by  chance  into  the  inferior  vena  cava,  and  thence  into  the  lungs. 
Their  eggs  are  distributed  therefore  especially  throughout  the  mucosa 
and  submucosa  of  the  ureters,  bladder,  and  rectum,  and  occasionally  also 
in  the  liver,  lungs,  kidneys,  and  prostate.  While  still  within  the  urinary 
passages  the  cylindrical  embryos  (miracidia)  covered  with  fine  cilia  may 


r 

Fig.  553.  Fm.  5.54.  i 

Fig.  .5.5.3.— DMfoma  hamatobium.     (After  Leuckart.)    iMale  and  female,  the  latter  lyinR  in  the  canalis  i 

gynaecophorus  of  the  former.    X  10.  j 

Fig.  .554.— Eggs  of  Di^foma   hcematobium.    (After  Leuckart.)    a.  Egg  with  terminal  spine  ;?>.  egg  < 

with  lateral  spine.     X  1.50.  [ 

develop.     Kartulis  found  them  also  in  the  skin  of  the  leg  and  foot,  and  | 

is  of  the  opinion  that  the  infection  may  take  place  not  only  through  the  ^ 

intestine,  but  also  through  the  skin.  jj 

The  deposit  of  eggs  causes  severe  inflammations  which  lead  in  part  to  | 

tissue-destruction  and  in  part  to  proliferations  of  the  tissue,  which  ap-  | 

pear  in  the  mucous  membranes  as  papillary  and  polypoid  formations.     In  jji 
the  bladder  it  may  lead  to  incrustations  and  formation  of  concretion^^ 
and  also  to  the  development  of  fistulous  tracts.     In  the  liver  the  process 
leads  to  a  connective-tissue  induration.     Following   the   inflammatory 

process,  a  development  of  carcinoma  may  take  place  in  the  bladder,  ! 

.seminal  vesicles,  prostate,  and  in  the  skin  (Kartulis).  < 

The  parasite  is  found  along  the  entire  eastern  coast  of  Africa,  and  I 

also  in  Zanzibar,  Tunis,  Lake  Xyassa,  in  Beyrout,  and  in  Sicily.     It  is  i 

most  common  in  Egyj)t,  where  about  twenty-five  per  cent,  of  the  native  i 

population  suflTer  from  the  disease.  | 

Literature. 

{Tfciitdiodrs.')  ^  : 

Albarran  ot  Bernard:  Tiimeiir  epitlu'-l.  duf  a  la  Bilharzia.     Arch,  de  med.  pxp..  1S97.  • 

Aschoff:  Eiu  Fall  v.  DLstoma  lanceolatuiu  in  (kr  iiienschl.  Leber.     Vircli.  Arch.,  130  ■, 

Bd..  1S92.  ,     .     ,  I 

Askanazy:  Dist.  fclineum  beim  Menschen.     Cbl.  f.  Bakt.,  xxviii.,  1900;  Aetiologie  der  | 

Katzenojielcrkrankung.     D.  med.  Woch.,  1904.  i 
Baelz;  Einijie  neue  Parasiten  des  Menschen.     Berl.  kliii.  Woch..  1SS3. 
Biehringer:  Arbeiten   z.   Entwickelungsgeschichte  de.s   LeberegeLs.     Biol.  Cbl.,  viii., 

issv,. 


1«,    j[ 

?SS    f 

rv  \i 


J 


isr.r$. 

ic.    Wifii 

nicil. 

Wor-li..  1N( 

klin.  Mel 

,  xxxi 

li.,  l.s.s;{. 

.     ('l)l.  f. 

Hakt 

,  xiii.,   IS'. 

CKSTODA.  7_'l 

Biermer:  Leberdistoma.  Schwciz.  Zeitschr.  f.  Ilcilk.,  ii. 
Bilharz:  Distonniinha'-'iuatobiuniu.  Verand.d.  llaniorfia 
Bostrom:  Leberdistoma  beim  Mcnschen.  Dent.  Arcli.  f. 
Braun:  Die  Wolmsitze  d,  eudoparasitischen  Trematodei 

Leberdistomen  d.  Hauskatze.     lb.,  xiv.,  1893;    Fiir  <l.  Mensclieii  lu-ues  Di.stoiiiuiiK 

lb.,  XV.,  1894;    Die  tierischeu  Parasiten  des  Meiisdien,  Wnrzburp,  JUOiJ. 
Brock:  On  the  Bilharzia  ILTiiiatobia.     Journ.  of  Tatli.,  ii.,  J893. 
Chaker:  ICt  udesurrhematiiried'EgyptecaustV  par  la  Hilliarzia  liaeinatobia,  Paris,  1890, 
Duflfek:  Dist.  hepaticuin  beim  Menschen  {,'■>{)  Exompl.  in  (lallenKiiiigen,  (ialleiil)la.se, 

MagiMi  u.  Diinndarm),  Wien.  kliii.  Wocli.,  19()2. 
Fritsch.  Zur  Anatomie  der  Bilharzia  haematobia  t'obl).     Arcli.  f.  milkr.  Aiiat.,  xxxi., 

1;-.SS. 
Goebel:  Bilharziakrankheit.     A.  f.  Schiffs- u.  Tropenliyg.,  19();{. 
Kartulis:  A'ork.  d.  Eicr  des  1).  haemat.  in  den  riilerleibsorg:ineii.     ^■irc]l.  Arch.,  99 

Bd..  1885;    Pathol.  Anat.  der  Bilharzia.     11).,  l.VJ  Bd.,  1898. 
Katsurada:  Dist.spathulatumn.  D.  Westermanni.   Beitr.  v.  Ziefrler,xxviii.,  1900  (Lit.). 
Leuckart:  Ueber  den  grossen  amerikanischen  Leberegel.     ("1)1.  f.  Bakt.,  xi.,  lUO'J. 
Loess:  Zur  Lebensgeschichte  der  Bilharzia  haematobia.     Cbl.   f.   Bakt.,  xvi.,   1894; 

Trematodenfaima  Aegyptens.     Zool.  Jahrb.,  xii.,  1899;   Cbl.  f.  Bakt.,  xxxiii.,  1892. 
Lutz:  Zur  Lebensgeschichte  des  Distonia  hepaticum.     Cbl.  f.  Bakt  ,  xi.,  1892. 
Meinecke:  Dist.  haematobium  in  d.  Blasenwand.     Jahrb.  d.  Ilanib.  Krankcnunst., 

v.,  1897. 
Odhner:  Distoma  crassum  (York,  iu  Ostasien).     Cbl.  f.  B.,  Orig.,  xxxi,,  1902. 
Peiper:  Trematoden.     Ergebn.  d.  allg.  Path.,  vii.,  1902. 
Poirer;  Contrib.   a  I'histoire   des   trematodes,  Paris,    188.1;     Xote  sur  mie    nouvclle 

espece  de  distome  parasite  de  I'homme,  le  distomum  Bathousi.     Arch,  de  zool.  exp., 

v.,  1SS7. 
V.  Ratz:  Leberegel  in  der  Milz  der  Schafes.     Cbh  f.  Bakt.,  xxvi.,  1899. 
Riitinaeyer:   Ueber  Bilharziakrankheit.     Mittheil,  a.  d.  Klin.  d.  Schwciz,  Bas(>l,  1.S9I. 
Schaper:  Die  Leberegelkrankheit  des  Haussaugethiere.     Deut.  Zeitschr,  f.  Tliicrined., 

XV.,  1889. 
Schauinsland:  Embryonalentwickehnig  der  Trematoden.     Jen.  Zeitschr.  f.  Natin-\v., 

xvi.,  1883. 
Scheube:  Die  Krankheiten  der  -\varmen  Lander,  Jena,  1903. 

Sonsino:  Discovery  of  the  Life  Hi.storv  of  Bilharzia  Ha-matobia.     The  Lancet,  1893. 
Ward:  Trematoda.     ReL  Handbook  ot'.Med.  Sc,  2d  ed,,  1903. 
Winogradow :  Eine  neue  Distomaart.     Cbl.  f.  allg.  Path,,  iii.,  1892. 
Yamagiva:  Zur  Aetiologie  der  Jackson'schen  E))ilep,sie  (Eier  von  Distoma  i)uhnonale 

im  Hehirn).     Virch.  Arch.,  119  Bd.;    Ueber  Lungendistomenkrankheit  in  Jai)an. 

Ib„  127  Bd.,  1892. 


2.    Cestoda  {Tapewonnfi). 

§  191,  The  tapeworms  are,/frf^^ro;•?».sr7rro^7o/'w(^>///// or  iiilr.sfinr,  wliicli 
increase  after  the  method  of  alternate  oeneralion  lhi<»n.uh  tlic  <icrnii  nation 
of  a  pear-shaped  primary  head  or  seolex,  and  leniain  united  to  the  hitter 
for  a  long  time  as  a  (usually)  h)ng,  baud-shaped  colony.  The  single 
segments  of  this  colony,  the  sexually  active  individmils,  or  proglottides, 
increase  in  size  the  m<n-e  ^videly  they  become  sei)arated  from  their  jdaee 
of  origin  by  the  fornuition  of  new  mend)ers,  bnt  ontside  of  this  are  <le 
void  of  any"^ontward  disting;uishin.<,'  ])ecnliarity.  The  ])eai-sha|)ed  head 
or  seolex,  on  the  other  hand,  is  ])rovided  with  from  two  to  four  sneker.s. 
and  usually  also  ^vith  curved  claw-like  liooks.  AN'ith  tlieai(l«>f  thes«' 
clinginj;- or.uans  tlie  tapewoi-ms  fa.sten  them.selves  to  the  intestinal  wall 
of  their  host,  Miiich  a])pearsto  be  invaiiahly  one  (d"  the  vertelnat*'  ani 
mals.  The  scolices  develop  fnnu  a  ronnd  embryo  liaving  fonr  to  six 
hooks,  and  are  found  as  the  so-called  "mea.sles"  in  the  most  diverse  oi-- 
gans,  chietly  the  parenchymatous  ones,  fnnn  which  Ihey  later  pass  by  a 
passive  mijiratiou  into  the  intestine  of  their  fn1nr(^  ho.st. 

The topeirorma  occurrhtr/as  jxirasitrs  in  hkdi  hchnv^  to  dilVerent  biniilies 
tin-  T(e)ti(((lw  and  the  J!(>i/irioccj>li(ili<l(r.     The  lirst oeenr  in  man  ••it  her 
as  ^'measles"  or  as  ta]»eworm.s,  the  latter  only  as  tapeworms. 
4(1 


722 


THE    ANIMAL    PARASITES. 


^  192.  Taenia  <>olium  in  its  fully  developed  condition  possesses  a 
length  of  2-;>  nieties.  The  head  (Fig.  5.").5)  is  of  the  size  of  a  small  pin- 
head,  is  spherical  in  form,  with  rather  i)i"ominent  sucking-cuiis.  The 
crown  of  the  head  is  not  infrequently  pigmented  and  bears  a  fairly  large 
rostellnm  with  about  twenty-six  plump,  close  hooklets  having  short  root- 
processes.  F. blowing  the  head  there  is  a  thread-like  iieck  of  about  an 
inch  in  length.  At  a  certain  distance  from  the  head  segmentation  begins, 
the  first  segments  being  very  short,  but  their  length  increases  with  their 
distance  from  the  head  (Fig.  556);  they  become  quadratic  and  finally 
longer  thau  broad.    The  mature  segments  appear  about  l-SO  cm.  behind  the 


A. 
Fig.  555.  Fig.  556.  Fig.  r 

Fig.  5.55.  -Head  of  Tasnia  solium  with  protruding  rostellum  (carmine,  lialsauu.    : :  50. 
Fk;.  558.— Half-developed  and  fully  matured  segments.    Natural  size.     (After  I.euckart.) 
Fig.  557.— Two  proglottides  with  uterus.     (After  Leuckart.)     X  2. 


head,  although  the  sexual  organs  are  fully  developed  in  earlier  segments. 
The  ripe  segments  (Fig.  557)  are,  when  stretched  out,  9-10  mm.  long, 
and  ()-7  mm.  broad,  and  have  rounded  corners.  The  sexual  opening  is 
situated  laterally  just  behind  the  middle  of  the  segment.  Tlie  uterus, 
which  is  filled  with  eggs,  jDo.ssesses  seven  to  ten  lateral  branches  which 
are  separated  from  each  other  by  a  wide  interval,  and  lu-eak  up  into  a 
varying  number  of  boughs  branching  like  a  tree. 

The  pai-enchymaof  the  body  of  mature  as  well  as  of  immature  pyo<jl()i- 
liiJes,  or  tapeworm  segments  (Fig.  55S),  is  divided  into  two  chief  layers, 
the  central  one  being  designated  the  middle  layer,  the  peripheral  one  as 
the  cortical  layer.  The  middle  layer  contains  the  sexual  apparatus  (Fig. 
558,  c,  d,  €,/,  ff,  h,  i,  I;  1,  m,  n),  as  well  as  the  water  vascular  system  (a), 
au  excretory  apparatus  which  traverses  the  whole  tapeworm  from  the  i 
head  to  the  last  segment  in  the  form  of  two  canals  lying  in  the  lateral 
border  of  the  middle  layer.  The  canals  are  connected  Avitli  each  other  at 
the  po.sterior  end  of  each  segment  (a')  and  also  send  out  numerous  fine, 
subdividing  branches  into  the  body-parenchyma. 


CESTODA. 


The  .sexital  appanitKs  consists  of  male  and  female  sexual  organs,  which 
lie  close  together.  A  number  of  small,  clear  vesicles  serve  as  leslicU's 
{c),  they  lie  chiefly  in  the  anterior  portion  of  the  niiddlc  layer  The  vas 
deferens  (e),    which  is  con- 


^^CXv^ 


nected  with  the  testicles  by 
the  seminal  duels  (<l),  emp- 
ties into  a  s;i-oov(mI  ]xipilla 
situated  on  the  lateral  border 
(It).  The  coiled  end  (/,  f/) 
lies  in  a  muscular  bay;  antl 
may  be  protruded  through 
the  sexual  opening  (cirrus). 
The  female  sexual  oldening 
lies  close  behind  the  male 
orifice  in  the  same  sexual 
cloaca.  The  vagi  na  ( / )  leads 
thence  to  the  posterior  border 
of  the  segment.  Before  this 
is  reached  it  widens  into  the 
seminal  vesicle,  and  behind 
this  into  the  fructifying  can- 
al and  the  so-called  "globular  body."  Tlu 
which  must  be  sought  in  the  immature  segments 
(k)  and  a  single  albumin  gland  (I) ;  these  are  s 


Fio.  .">;xS.— Seprment  of  Ta:iiifi  solium  with  fully  tleveloptnl 
sexual  apparatus.  (After  StimuitT.)  ^1,  Surfucc  view  of 
segnifut;  />',  ImhiI.t  of  next  anl.Ti.ir  si'!.Mii.'rit ;  (',  that  of 
next  iiosi.TiiirsrL'iiiciit;  (/,  Icii-iiinliiial  ex. -ivi.irv  trunk  ;  d,. 
transvnst'  auaslni,i,,sis ;  /.,  l.iiiLnliiclinal  plasiiia-v.-ss.-l;  .. 
testicular  vcsu-l.-s;  ./,  s.-iiiiual  .lu.-ts;  i,  vus  <l.-f.-ivris:  ', 
i-irrus-batr  with  cirrus  ;  (/,  porus  KeJiitiilis ;  /(.  Iwrder  papilla  ;i. 
vagina;  /f,  ovaritnu ;  /,  albuniin-glan.l ;  in,  sliell-Klanil,  and 
oviduct  in  front  of  same ;  ii,  uterus. 


Ig    n|'o;i 
ihJroN 


geiiii-picpaii 
consist  of  a  (h 
c-like  or  tiil)ul;ir  (.r-:iiis 
lying  in  the  posterior  portion  of  the  segment  and  communicating  with  tlu» 
globular  body.  The  latter  is  joined  to  the  aiiterioily  locat<'d  uterus  (//), 
which  at  the  time  of  sexual  maturity  forms  a  straight  canal.  AN'hcn  the 
eggs  enter  the  utei'us  from  the  globular  body,  in  which  they  ]»a.ss  theii' 
first  stage  of  development,  the  above-mentioned  lateial  luaiiches  si»rout 
out  and  become  tilled  with  eggs.  During  this  pi-ocess  the  icmjiiiiing  sex- 
ual organs  disappear. 

The  co>iicallai/er  of  the  2)>'Offlotti(l('S  is  essentially  miisciihir  in  natiirr, 
but  in  addition  contains  a  larger  or  smaller  niinibcr  of  .s()-c;dled  cjilcarcdiis 
bodies,  which  are  not  entirely  wanting  in  the  middle  layer  as  w«'ll.  The 
musculature  consists  of  smooth  fibres,  which  foiin  special  grouj)s  in  the 
suckers  of  the  head.     The  surface  of  the  tapeworm  is  coveied  with  :i 

clear  cuticle,  which  foniis  1  hr  hooks 
on  the  heads. 

The  rf/(/s   ill    tlir  onirif  :ii<'  thin- 
ski  lined,    ]»ale  and    yellow,    nearl.\' 
globular  cells.      In  tluMitiMus  t hey 
change  into  yellow  l);dls  ha\  ing  a 
thick,  moi-e  or  less  ojjaiiue   shell, 
cover<*d  with  closely  set     si)icides 
(Fig.  551),  a).     The" latter  is  (.ften 
siii-roiinded   by  a  second  ]:i\vv,   an 
jdbuniinous    envelope   (h)    limited 
by   a   nieinl)i;iiie;  :ind    in    it    there 
aie  embedded  giaimles  riyriiniliv  e 
vit<'lliiie   membrane).     The   diam- 
eter of  the  eggs,  not  including  the  vitelline  membrane,  is  about  (>.():$  mm. 
The  thick-shelled  spheres  are  not  undeveloju'd  eggs,  l»ut  cont;iin  an 
embryo  with    six  booklets.     An  intra-ut<M-ine  development  of  the  em- 
bryo therefore  takes  place,  the  ripe  segments  are  pregnant  animals. 


Fig.  .",;-,!> —Eggs  of  Tamia  snlhwu  h.  With  primi- 
tive vitelline  membrane ;  a,  without  primitive  vit.-l- 
Mne  membrane.    (After  Leuckart.)     X  m). 

FtG.  r>60.— Cysticereus  cellulosiB,  with  fully  devel- 
oped head  in  situ.    (After  Leuckart.)    X  4. 


724 


THE    ANIMAL    PARASITES. 


^,4 


c- 


The  further  development  of  the  embryos  enclosed  iu  the  brownish  shells 
takes  place  ordinarily  in  a  new  host.  Should  they  gain  access  to  the 
stomach  of  a  ho(/,  the  egg-shell  is  dissolved,  and  the  embryos,  thus  set 

free,  penetrate  into  the  stomach 
or  intestinal  wall.  Thence  they 
pass  either  by  the  blood-stream 
or  by  an  active  migration 
through  the  tissues  into  this  or 
that  organ.  Having  reached  a 
resting-i)lace,  the  embryos  un- 
dergo various  metamorphoses 
and  become  changed  inside  of 
two  or  three  months  into  a  cyst 
filled  with  serum  (Fig.  560),  the 
inner  wall  of  which  shoots  forth 
into  a  bud  from  which  there  de- 
velops a  new  taj)eworm  head,  a 
scolex,  as  well  as  a  sac  enclosing 
the  same,  a  receptaculum  scolicis. 
The  cyst  containing  a  taj)e- 
worm  head  is  known  as  a 
♦'  measle  "  or  cysticercus  ce\\= 
ulosae.  The  scolices,  when  fully 
developed,  possess  a  circle  of 
booklets,  suckers,  a  water-vas- 
cular system  and  numerous  cal- 
careous bodies  in  their  body- 
parenchyma.  If  they  gain  access 
to  the  human  stomach,  the  cyst 
is  dissolved,  and  there  develops, 
through  the  formation  of  seg- 
ments from  the  scolex  (Amme), 
a  new  chain  of  proglottides,  a 
new  Tienia  solium. 

The  Tcenhi  solium  inhabits  the 
small  intestine  of  man,  and  is  ac- 
quired by  the  eating  of  uncooked 
pork,  since  the  "measles"  belonging  to  this  parasite  occur  almost  solely 
in  the  hog  and  in  man.  By  means  of  its  sucking-cups  and  its  circlet 
of  hooks  it  clings  firmly  to  the  mucosa  of  the  intestine ;  the  remaining 
portions  float  freely  in  the  intestine.  Usually  but  a  single  i^arasite  is 
present  in  the  intestine,  although  the  i^resence  of  several  at  the  same 
time  is  not  rare.  Occasionally  as  many  as  thirty  or  forty  have  been  ob- 
served in  one  individual.  They  excite  irritation  of  tlie  intestinal  mu- 
cosa, colic,  and  reflex  disturbances  of  the  central  nervous  system. 

The  "  measles"  occur  in  the  tissues  of  the  hog,  sometimes  singly, 
sometimes  in  great  numbers  (Fig.  501);  and  individual  organs,  as,  for 
example,  a  muscle  or  the  heart,  may  be  thickly  studded  with  them. 

In  man,  cysticerci  occur  in  the  most  varied  tissues — the  muscles,  brain, 
eyes,  skin,  etc.  In  the  meninges  and  in  the  brain  the  measle  may  ap- 
pear in  the  form  of  mulberry  or  grape-like  collection  of  cysts,  known  as 
cysticercus  raeemosus  (Zenker).  The  cysts  are  for  the  greater  part  sterile, 
though  some  of  them  may  contain  a  scolex. 

The  imi)ortauce  of  the  measle  depends  upon  its  location,  but  is  in  gen- 


501.— Cysticerci  of  the  Tcetiia  soZmm,  in  tlie  epi- 
cardium  and  myocardium  of  a  hog. 


CESTODA. 


725 


eral  slight.  Its  proseuce  in  the  brain  often  e;iuses  se\ei<'  distmltaiucs, 
but  in  other  eases  all  signs  of  disease  maybe  laekiiig.  Loeally  it  ex- 
cites a  slight  intlaniniation,  \vhieh  leads  to  a  tliiekening  of  the  eonnei-tivc 
tissne  in  its  immediate  neighboihood.  The  eyst  may  retain  its  vitality 
for  years.  After  the  death  of  the  seolex  the  eyst  eontraets  and  there  is 
deposited  Avithin  it  a  chalky  mass.  The  liooklcts  are  ])r«'s«'rv«'<l  in  this 
mass  for  a  very  long  time.  Iiifection  with  the  "iiH'ash-s"  follows  the  in- 
trodnction  of  eggs  or  j)roglottides  into  the  sloniacli  <»f  man. 

Taenia  mediocanellata  or  saginata  snr- 
l>asses  the  Taiiia  solium  not  only  in  length, 
as  it  measnres  4-7  metres  and  moic,  bnt  also 
in  its  breadth  and  thickness,  as  well  as  in 
the  size  of  the  ])roglottides  (Fig.  .">()'_'). 

The  lirod  is  de\-oid  of  i-ostellnm  and  circle 
of  booklets  (Fig.  r)(;:>),  has  a  Hat  crown  and 
fonr  large,  powerfnl  snckers,  -w  hicii  arc  nsn- 
ally  snrronnded  by  a  black  border  of  i)ig- 
ment. 

The  c(/ffs  resend)le  those  of  2\vnla  solium. 
The   fnlly  develojied  pregnant  ntrrKfi  (Fig, 
.~)64)  has  a  large  nnmber  of  lateral  branches 
_  which  rnn  close  to  each  other,  and  instead 

f  s  11^  of  branching  dendritically  di\  ide  dichotom- 

/    B      ^        N\         ,1      }        onsly.     The  sexual  opening  lies  back  of  tln^ 
/     F      i  I        r  j|jy       middle  of  the  lateral  border.     Tlu',  segments 

^  x         WK^        discharged  spontaneously  are  for  the  greater 

part  empty  of  eggs. 


111. 


Fig.  563.— Portions  of  a  Ttenia  mgiiiata.    (AfU-r  Leiickari.)     Natunil  size. 
Fig.  5f>3.— Head  of  Tivnia  sauinatcu  retnicted.    Black  j»l»^mt'ntatl<.ii  in   aii.l  1m-Iw.-.. 
Unstained  glycerin  preparation.    X  :*). 

Fig.  504.— Segment  of  Tcc/aVt  .sa!//»«(f(.     (.\fter  I.euckart.)     X  K'- 


The  "measles"  are  fonnd  nsually  in  tli.-  nniscles  and  Ihe  heart,  nioie 
rarely  in  the  other  organs  of  rotflr  (('i/.sfirrrnis  horis).  Tliey  are  soinewliat, 
smaller  than  the  measles  found  in  jxuk. 


726  THE    ANIMAL    PARASITES. 

The  development  follows  a  course  similar  to  that  of  T(ema  solmm. 
Mdlformatious  of  tins  tapeworm  are  of  very  frequent  occurrence. 

The  parasite  is  acqnired  by  man  through  the  eating-  of  raw  beef.  It 
has  uot  been  definitely  settled  whether  the  "  measles  "  of  this  worm  occur 
in  man,  but  some  authors  (Arndt,  Heller)  believe  that  such  au  occur- 
j-ence  does  take  place. 

B;v'  means  of  its  powerful  suckers  the  parasite  is  able  to  cling  very 
firmly  to  the  intestinal  wall.  Stieda  has  observed  a  case  in  which  a 
taenia  15  cm.  long  had  penetrated  through  the  wall  of  the  duodeiuim  into 
the  pancreas,  and  had  caused  tissue-necrosis  and  hiemorrhage  in  its 
neighborhood. 

Taenia  cucumerina  or  elliptica  is  15-20  cm.  long,  and  possesses  a  head  Avitb  ros- 
tellmn  and  circle  of  liooklets.  It  is  of  very  frequent  occurrence  in  dogs  and  cats,  but  is 
rare  in  man.  Its  cysticercoid  inhabits  the  louse  and  flea  of  the  dog,  more  rarely  the 
flea  of  liuman  l>cings  ((rrasxi). 

Taenia  nana,  a  small  tapeworm  of  from  8  to  15  mm.  in  length,  has  a  head  with 
four  suckers  and  a  circle  of  booklets.  It  has  been  observed  chiefly  in  Egypt  and  in 
Italy.  B.  Orassi  was  able  to  obtain  several  thousands  of  specimens  from  two  Sicilians 
who  had  suft'ered  from  severe  nervous  disturbances.  According  to  his  investigations, 
the  tcPnia  passes  its  entire  development,  from  the  embryo  on,  witliiu  the  same  iiost. 
Viscontt  (Rendiconti  R.  Istituto  Lombardo,  xviii.,  1886)  found,  at  tlie  autopsy  of  a 
young  man  from  nortliern  Italy,  great  numbers  of  Tcenia  nana  in  the  lower  portion  of 
the  ileum.  In  Germany  it  has  been  observed  in  only  a  few  cases  (Mertens,  Leichtcnstern, 
RMcr). 

Taenia  diminuta  {Ilud.)  ov  flavopuncta  (Weinland),  ininima  (Grassi)  is  a  tapeworm, 
20-60  mm.  long,  and  has  a  head  without  booklets.  It  is  of  common  occurrence  in  rats 
and  mice,  and  iias  also  been  observed  in  a  few  cases  in  man.  According  to  Grassi  and 
Rovelli,  the  measles  live  in  a  small  butterfly,  as  Avell  as  in  beetles. 

Ton  Li/isfo/r  lias  recently  (iesciibcd  as  Taenia  africana  a  large  tapeworm  with 
scolex  devoid  of  booklets,  which  he  observed  among  the  negroesof  German  East  Africa. 

Besides  those  which  also  occur  in  man,  tienite  are  of  frequent  occurrence  in  the 
domestic  animals,  both  in  the  carnivoia  and  in  birds,  as  well  as  in  the  herbivora. 

T'nit'c  wfTf/inafa  of  the  c}ogj<i  a  ta-peworm,  1-5  m.  long,  provided  with  a  double 
circle  of  booklets.  Its  cysticercus  forms  cysts  (cysiicerciis  ienincollis)  of  varying  size 
in  and  under  the  serous  membranes  of  sheep,  cattle,  goats,  and  hogs. 

Tii'/iia  sernda  is  a  t;enia  found  in  the  dog.  It  is  50-100  cm.  long,  and  possesses  a 
circle  of  booklets.  The  cysticerci  {ci/sticercus  2)'isifor)ins)  are  foimd  in  rabbits  and 
hares. 

Ta'7na  ccenuriis  is  a  tapeworm  of  the  dog,  40-100  cm.  long,  and  is  provided  with 
booklets.  It  passes  its  cystic  stage  most  frequently  in  sheep,  where  it  seeks  the  central 
nervous  system  and  forms  cysts  varying  in  size  from  that  of  a  millet  seed  to  that  of  _a 
hen's  egg,  Avhich  contain  great  numbers  of  scolices.  Its  piesence  in  the  brain 
{caiuirii.s  ci  i;I/j'alis)  gives  rise  to  the  so-called  " staggers  "  of  sheej). 

y'l'  iiiii  'ji/i''iita  (10-25  cm.  long),  Tcenia  mamillana  (1-3  cm.  long),  and  Tcmia  perfo- 
liata  (8-5  cm.  long)  occur  in  horses.  Tmnia  expnnsa  (4-5  m.  long)  and  Tcenin  dcnticti- 
lata  (25-80  cm.  long)  are  the  common  tapeworms  of  cattle.  Further,  still  other  forma 
of  tteniae  occur  more  rarel}^  as  parasites  in  sheep  and  cattle. 

Literature. 

(Tamia  as  Intestinal  Farasites.) 

Blajichard:  Cestodes  monstrueux,  Paris,  1894,  ref.  Cbl.  f.  Bakt.,  xvii.,  18i»5. 
Blochmann:  Plasmatische  Langsgefiisse  bei  Taenia  sag.  u.  Taenia  sol.     C'lil.  f,  Bakt., 

xii.,  1892. 
Braun:  Die  tierischen  Parasiten  des  Menschen,  Wurzburg,  1903. 
Erlanger:  Der  Gcschlechtsa])parat  v.  Taenia  echinococcus.    Zeitschr.   f.  wiss.  Zool., 

50  Bd..  1890. 
Grassi:  Die  Taenia  nana.    Cbl.  f.  Bakt.,  i.  u.  ii.,  1887;  Bandwurmentwickelung.      lb., 

iii.,  1888;  Entwiekelungscyklus  von  Taenia  cucumerina.     lb.,  iv.,  1888. 
Grassi,  B,,  u.  Rovelli,  G.:  Embryolog.  Forschungeu  anCestoden.     Cbl.  f.  Bakt.,  v  , 

1889. 
Guillebeau:  HelminthologischeBeitrage.     Vlrch.  Arch.,  119  Bd.,  1890. 
Hiiber:  Bibliographic  d.  kiln.  Helminthologie,  1-4  Hef te,  Mlinchen,  1891-92. 


Kciiixococci  s.  727 

Kahane.   Analomic  von  Tju'iiia  i)crf()li:it;i.     Zcilschr.  f.  wiss.  Zool.,  \\\iv. 

Kitt:   I.i'hil).  (1.  iwthol.-aiiat.  Diauiiostik,  ii..  Stntl,<:arl.  IS!),"). 

Leichtenstern :    Taenia  nana  n.  tlavojinnctata   licini    Mcnschcn.      Drnl.    mcd.  Wi.cli  . 

1S!)'J. 
V.  Linstow:   Taenia  nana  n.  muiina.     .Icii.  Zcitsclir.  I'.  Nalnrwiss..  ISJMi. 
Lutz:   P.cohaclit.  iih.  Taenia  nana  u.  tlavoimnctata.     ("hi.  t.  Hakl..  \vi..  islU 
Mingazzini :    Sur  Ic  mode  (ra(ilu''si()ii  drs  ccstnidr-;  a  la  jiaini  iMii'stinalr.      Anh.  itjti. 

de  l)iol..  xxxii.,  ISSCJ. 
Niemie:    Tel),   d.    Nervensvst.iu  d.  C.-.in.i.n.      Ail..    .•..  d.  Z<h.1.  Inst.   d.  I'niv.  Wiin 

\ii..  1SS(). 
Nuttall:    The   Poison-;   (liven    Oil    In    I'aiasjiir    Worms  in  Man  and  AinniaN.      Ain.i. 

Nat.,  1S1IJ». 
Peiper:  Tiiier.  Parasiten  d.  >Ien.sehen.     Ergehn.  d.  allg.  Patli.,  iii..  1M!(7  (I.il.),  ".  vii.. 

i!»ii'2  (lat.). 
Roder:  Taenia  nana  in  Deutseldand.     ^liinch.  nied.  Woch..  1899. 
Somnier:  Ueber  Bau  n.  Entwiekehniu-  der  (xesclilechtsorganc  v.  Tu<'nia  inrdicu  anellaii 

u.  Taenia  solium,  Jjeipziii".  1NT4. 
Stieda:   Dnielibohrnnu,- d.  Dnodennms  u.  d.  Pankreas  dunh.  c  T-iniai'.     <I>1.  1.  Uaki 

xxviii.  1900. 
Stiles:  The  Tvpe  Speeies  ol'  the  Cestode  C}enns  ll,i,„i„;U,,;s.      j'.ull.  l'.  .s.  Hvi:.  ],al... 

No.  13,  :Mav,  1903. 
Stiles  and  Hassall:  ARevisionof  the  Adult  Cestodis  orcatiic.  Shei  p,  and  Allied  Ani- 
mals, Washington,  1884;  Tapeworms  of  Poult iv,  Washington.  ISiHI.     The  Insp<'. 

tion  of  Meats  for  Animal  Parasites.  U.  S.  T)ept.*Agr.  Bull.,  19,  18!is. 
Ward:    A  New    Human   Tapeworm  {Tn'iiio  y»if>im).     West.  Med.  l{e\..  isiir,;  Zo..l. 

Anz..  1897;  Cestodu.     Kef.  Ildh.  of  Med.  Se.,  2d  ed.,  vol.  ii. 
Weinland:  Human  Cestodes,  Cand)ridge,  1858. 
Zschokke;  Studicn  liber  den  anatom.   u.  liistol.  Bau  der  Cestodf.     Cl.l.    I'.  IJakt.,  i., 

ISST;  Keeh.  sur  la  structure  des  Cestodes,  Bille.  ISSi). 

(('i/stircrciis  in  Jlaii.) 

Askanazy:  (,'vstirerkeiibildnng  an  der  Hirnbasis.     Beitr.  v.  Ziegler,  vii.,  1890. 
Bitot  et  Sabrsizes:  Etude  sur  les  eysticerqucsen  grap|)e  de  reneeidialret  dc  la  inoClle 

(he/,  riionime.     Gaz.  med.  de  Paris,  1890. 
Dolina:  Intraocularcr  Cysticoreus.     Beitr.  v.  Ziegler.  v..  1889. 
Hirschberg-:  Cysticercus  im  Auge.     Eulenburg's  Realeneyklop..  188.'i. 
V.  Kahlden:  Cysticercus  d.  IV.  Ventrikels.     Beitr.  v.  Ziegler,  xxi.,  1897. 
Kratter  u.  Bohmig:  Freier  Gehirneysticercus.     Beitr.  v.  Ziegler,  xxi.,  1897. 
Lewin:    Gvsticercus  cellulosa'   der   Haul.     Eulenburg's   Realenevklo]).,    iss."i  ([ji.): 

Arch.  f.  Derm.,  26  Bd.,  1894  (Lit.). 
Mennicke:  Cysticercus  racemosns  d.  Gehirns.     Beitr.  v.  Ziegler,  xxi..  1897. 
Richter:  Cysticercus  racemosus  in  den  innereu  Meningen.     Pnig.  med.  Woch.,  1891. 
Zenker:   Ui'ber  i\vn  Cysticercus  racemosns  des  (Jehirns.  Bonn,  1S8-.'. 

S  li>.>.  The  Tsenia  echinococcus  lives  ill  tlir  inU-.^linal  ciiinil  of  lii.' 
do<;-.  It  is  4-.-)  mill,  long  and  p<)sses.ses  only  l<»iir  so-iiiciils,  llir  iii<.-i 
posterior  of  iliese  surpassing- in  leugili  all  tlie  rest  |>nt  loocllier  (  l-'ig. 
5o;5). 

The  small  hooklelshaAc  coarse  root  pioces-sj-saml  :ire  impianfed  ii|m.ii 
a  rather  bulging  rostellnm.  TIhmi-  number  runs  trom  altoni  tliirl.v  l.. 
fifty. 

The  cyst=worm  (hydatid)  alone  is  Ioiiik:  in  in:in.  ll  ivsiill>  fiom 
tlie  introduction  of  ta'uia  eggs  into  Ihe  int<'sliiial  canal. 

If  the  embryo  wanders  from  Ihe  inleslinal  canal  into  any  organ,  il 
clianges  into  a  c//.s/,  wliich  is  not  capable  of  active  motion.  It  <-onsist.s  of 
an  outer  hnnrllitfrd,  veiv  elastic  r»//c/r  (Fig.  r^M,  <i)  and  a  parenchyma 
tons  layer  (/>)  lying  internal  to  this,  consisting  (.f  granular  mas.ses  ami 
cells,  and  containing  muscle-fibres  an<l  a  vascidar  .sy.stem.  When  llu- 
cyst  has  reached  about  the  size  of  a  Malnut  (sometimes  t-arliei  >,  there  are 
tormed   from   the    parenchymatous  layer  small   hrn(,>lr„p.sHlrs  (o  whidi 


728 


THE    ANIMAL   PARASITES. 


produce  a  great  number  of  scoUces.  The  first  stage  of  these  tapeworm 
heads  consists  of  coarsely  granuhir  protoplasmic  masses  (d)  lying  in  the 
wall  of  the  brood-capsule;  these  develop  further  and  show 
cavities  (e)  communicating  with  the  cavity  of  the  brood- 
capsule,  and  later  become  differentiated  into  a  tapeworm  head 
(/)  furnished  with  a  circle  of  hooklets.  The  head  {h)  which 
now  protrudes  into  the  lumen  of  the  brood-capsule  (g,  h)  is 
about  0.3  mm.  long,  possesses  a  rostellum  with  small,  j)lump 
hooklets,  four  suckers,  a  water-vascular  system,  and  numerous 
chalky  bodies  in  its  parenchyma.  Frequently  the  anterior 
part  of  the  body  is  telescoped  into  the  posterior  part  {(/). 

In  many  cases  the  echinococcus  cyst  remains  single. 
Its  only  change  consists  in  an  enlargement  to  the  size  of  an 
orange  or  fist,  through  the  formation  of  new  brood-capsules 
and  heads.  The  surrounding  tissue  forms  a  connective-tissue 
capsule,  in  which  the  cuticular  cyst  lies.  The  cavity  of  the 
cyst  is  filled  with  a  clear  fluid,  which  does  not  coagulate 
through  boiling  or  on  the  addition  of  acids,  and  contains  none 
or  but  little  albumen,  but  on  the  other  hand  does  contain 
sodium  chloride,  calcium  oxalate,  triple  phosphates,  uric  acid, 
sugar  (in  the  liver),  and  often  also  cholesterin.  The  brood- 
capsules  are  always  situated  on  the  inner  surface,  in  case  they 
are  not  mechanically  dislodged ;  and  are  visible  through  the 
transparent  parenchyma  as  small  white  i^oints.  Occasionally 
the  cyst  remains  sterile. 
In  many  cases  daughter=cysts  (Fig.  567,  c)  are  formed.  Their  de- 
velopment proceeds  in  the  depth  of  the  cuticle  independently  of  the  real 
parenchymatous  layer.     Between  two  lamellte  of  the  cuticle  there  arises 


Fig.  565.— 
FU'll-gTown 
Tsenia  echino- 
coccus. (Af- 
ter Leuckart.) 
X  13. 


Fk..  ">(.().— Wall  of  ail  ei-liinococcus-cysl  cciritaining  broori-capsules  anil  scollces  (alcohol,  cariiiiae).  a, 
Chltinous  membrane ;  t>,  parenchymatous  layer  with  vesicular  cells ;  c,  brood-capsules ;  d,  f,  /,  f,  h, 
Bcohues  lu  dillereut  stages  of  development.     X  100. 


a  collection  of  granules,  which  surround  themselves  with  a  cuticle,  and 
thereby  become  the  centre  of  a  new  set  of  layers.  As  the  number  of 
layers  increases,  the  cavity  grows  larger  and  the  contents  become  clear. 


ECIIIXOCOCCl  s.  72«j 

If  the  (lauo-litor-cysts  grow  they  Iml-v  out  the  wall  of  the  niollici-cNNt 
like  II  hernial  sac,  until  it  finally  .uivcs  way  and  liberates  its  e<)nt<'iils. 
If  they  now  i)ass  ontM-anl  by  the  side  of  llic  parent  cyst.  tli»">  ..btain  lic.m 


--^P^K^. 


Fig.  567.— Echinococcus  hudatidosus.  a.  Surface  of  liver;  7).  indurated  connective  tissue;  c, 
daughter-cysts  within  a  parent-cyst,  which  has  been  opened  by  an  incision ;  </,  adhesions.  Three-tlXtha 
natural  size. 

the  parenchyma  in  wliich  they  lie  an  external  eai)sule  of  ('(ninccliNc  tis- 
sue, and  then  produce  brood  ca])8ule.s  in  the  .same  mannci-  as  the  |iiiiii;ii\ 
cysts  arising  from  the  six-hooked  end)ryos. 

An  echinococeus  with  an  exoffcnoiDi 2)roJif('ratio)i  isealU'd  echinococcus 
granulosus  {HcoJecqiariens  Kiichenmeister),  oi-  sometimes  also  echinococ- 
eus veterinorum  from  the  fact  that  it  is  of  fr<'(nieiit  occni  icucc  among 
the  domestic  animals. 

A  second  com])Ound  form  of  the  ecliiiiococciis  is  the  echinococeus 
hydatidosus.     It  is  characterized  by  the  presence  of  inm-i-  (hniiilihrriists 
(Fig,  r)(;7,  c).     According  to  statements  ma<le  by  Naunyii.  and  also  con 
firmed  by  Leuckart,  the  scolices  and  brood-cajjsnlrs  iindcigo  a  r\stic 
metamorphosis,  and  so  become  changed  into  danglitcr c.xsts  wliidi  ocia 
sioually  produce  grand-daughter  cysts.     Thiough  the  foiination  of  nnmcr 
ous  daughter-cysts  the  chief  cyst  may  attain  a  very  large  size. 

The  infection  of  man  follows  the  ingestion  of  tlie  eggs  of  the  ta'nia 
which  occurs  in  dogs.  The  cysts  ai-e  most  often  fonnd  in  tiie  liver, 
but  the  echinococeus  occasionally  occnis  in  the  most  diverse  organs— for 
example,  in  the  lungs,  spleen,  kidneys,  intestine,  in  a  bone  or  in  the 
heart.  With  the  exception  of  the  distuibance  of  the  tissues  from  press- 
ure and  of  the  local  inflammation  wliich  it  cau.ses  (tlie  latter  leading  to 
the  formation  of  a  connective-tissue  capsule  in  many  organs )  t  he  cyst  often 


ISO 


^HE    ANIMAL    PARASITES. 


produces  iu>  liarmfnl  effects  upon  the  affected  individual.  It  often  dies 
ou  attainiiiii  a  certain  size  (tliat  of  a  ^yalnnt  to  tliat  of  an  apple),  the 
fluid  is  absorbed,  the  cyst  contracts,  and  there  remains  within  it  a  fattA , 
cheesy  detritus,  which  often  calcifies  to  a  mortar-like  mass.  The  hook- 
lets  are  preser^•ed  for  a  very  long  time. 

In  other  cases  the  echinococcus  becomes  larger,  particularly  when 
endogenous  or  exogenous  daughter -cysts  develop.  It  may  become  dan- 
gerous through  its  size  alone.  ScAere  inflammations  are  occasionally 
l^roduced,  particularly  after  trauma  or  after  rupture  of  the  cyst  into  one 
of  the  body-cavities.  Ruptuie  into  a  blood-A essel  may  also  occur  and 
lead  to  the  metastasis  of  cysts  and  an  embolic  blocking  of  vessels.  In  more 
favorable  cases  rupture  may  take  place  externally  or  into  the  intestines. 

The  spontaneous  spread  of  brood -capsules  and  scolices  in  the  same 


cl 


Fig.  568.— Transverse  section  of  an  Echtnococciis  mult  Hoc  ularis.    o,   Alveolar  echinococcus  tissue;  h, 
liver  tissue ;  c,  cavity  produced  by  softening  ;  (?,  fresh  nodules.    Natural  size. 

host,  as  well  as  the  experimental  transplantation  of  the  same  into  another 
host  (Alexinsky,  Deve)  may  lead  to  the  formation  of  new  cysts. 

Tlie  form  of  the  parasite  known  as  echinococcus  alveolaris  or 
multilocularis  presents  itself  as  a  hard  tumor,  situated  usually  in  the 
liver,  larely  in  other  organs  (brain,  spleen,  adrenal),  and  possesses  an 
alveolar  structure  (Fig.  .508),  in  that  a  firm,  dense  coiniective-t  issue  mass 
encloses  numerous  cavities.  Its  contents  are  translucent  and  gelatinous, 
or  consist  of  fluid  and  a  gelatinous  substance.  The  cavities  ai-e  in  part 
spherical  and  in  part  irregular  in  shape.  Usually,  through  the  soft- 
ening and  disintegration  of  the  parenchyma,  ulcerative  cavities  (c)  are 
formed.  In  other  i>laces  the  tissue  is  fibrocaseous,  necrotic  or  calcified,  or 
is  impregnated  with  bile.  At  times  the  caseation  of  the  prolifeiating  tis- 
sue is  the  most  ])rominent  feature  of  the  process;  at  other  times  the  alve- 
olar .st  lucture.  "Wlieii  the  development  of  the  colonies  has  progressed 
further,  there  aj^pear  in  the  tissue  gray  and  yellowish  nodules  (d)  in  which 
cavities  containing  colloid  plugs  (chitin-cysts  and  coils)  are  developed. 


FCl  I  IN  ()(•()(  (IS.  7;il 

The  cxiiuisito  alveolar  stnu'tiiic  lias  ^iveii  lise  to  the  theory  that   Ihi^ 
forinot'eehiiioeoeeiis  is  an  alveolai-,  eoHoid-eontaiiiiii^Mmiioi- oV  the  livci. 
Virehow  first  reeo.uiiized  the  true  iiatiiie  of  tlu' eoiidit ion,  and  demon 
strated  tliat  the  so-ealled  colloid  masses  wei'e  eciiinoeoeeiis  cysts. 

According-  to  the  invest  i-;at  ions  of  :MrlniU«»\v  Raswcdcnkow  the  :ilv«- 
olar  echinococcus  is  to  be  i<\i;ardcd  as  adillVicnt  species,  wliieli  increases 
in  the  tissue  of  the  host  in  a  ix'culiai-  mannei-.  snujicstiiii;-  the  mode  oi 
developmeut  of  the  Trematodes;  and  in  many  cases  spreads  by  bolli 
hteiuatogeuous  and  lynii)ho<;enous  metastases  from  tlie  primary  focus  of 
development  to  other  orjians  (lym{)li-<;lan(ls,  lunj;s,  brain}. 

Siuuild  the  alveolar  echinococcus  occurring-  in  any  or<;an,  as,  for  ox- 
ample,  in  the  liver,  encroach  U]>on  llie  neiuldjorinj;-  tissnes,  there  aie 
found  in  the  Litter  finely  grauuhir  uiultinnch'ated  ]M(>to]»hismic  stiuct- 
ures  surrounded  by  granulation  tissue.  Later  small  <-liitinous  cysts 
develop  or  a  folded  uiembrane  stndtled -with  u ra aula r  masses,  whih^  the 
^granulation  tissue  becomes  changed  into  iibruus  connect i\('  tissne.  "J'he 
majority  of  the  cysts  remain  sterile.  Scolices  de\-elop  only  in  a  few. 
Ovoid  grauular  structures  with  a  thin  mi'nd)rane  may  be  foiined  and  are 
regarded  by  ^Feluikow  as  eudiryos.  The  chitinous  membranes  which  lie 
in  the  gi-auulatiou  tissue  are  often  suii-onnded  by  giant -cells. 

The  life-hist-ory  of  the  alveolar  echinococcus  outside  of  the  paren- 
chj'ma  of  the  organ  is  unknown  ;  the  feet  ling  to  dogs  has  given  no  posi- 
tive results.  It  appears  that  the  embryos  and  scolices  of  the  same  are  not 
capable  of  development  in  the  intestine  of  tla^  dog. 

The  ordinary  echinococcus  is  widely  distributed,    thongii   not    \eiy 
common.     It  is  of  most  frequent  occuri-ence  in  Iceland,  where  1  1h'  i  iihabi 
tants  live  in  very  close  association  with  dogs.     The  alveolar  echinococcus 
has  been  observed  chiefly  in  Switzerland,  South  (Jermany,  Austiia,  and 
in  Russia. 

Literature. 

[KchiiKK-occits.  ) 

Abee:  Uchor  iiiultiloculann  Echinococcus,      Vircli.  Arcl...  I.",:  P„l..  ]S9!). 
Alexinsky;   Vcrimpfun<i- von  Eciiinococcus  in  d.  E.itu.liholilc.      I.anircnlu-ck's  Arcii., 

oG  Bd.,  1898. 
Bider:  Echinoc.  multilocul.  dcs  Gchirns.     Vircli.  Aicli.._  III  i'.d..  l^'-i"'. 
Carriers:  De  la  tumour  liydatique  alvcolairo,  Paris,  isfis. 
Deve:  De  recljinococcose  secoudaire,  Paris,  1901. 

Doebbelin:  lOiochenechinoiiokkeii  d.  Bcclicns.     Dent.  Zcitsclir.  f.  (JMr..  is  i;d  .  isiis 
Erlanger:  Dcr  Geschlechtsapparat  d.  Taenia  echinococcus.     Zcilsdir.  I.  \\  i^s.   /(...|., 

oO  lid.,  1890. 
Gerulanos:    Multiple  Muskelechinokokken.     l)<ut.   Zciiscin.    f.   Cliir..    |s   j'.d  .   ts'.is 

(bit  ). 
Guillebeaii:  Histologic  desmultiloculilrcn  Eciiinococcus,      N'iicli,  Arch,,  119  lid.,  I«90. 
Houzel:  Cystcs  liydatiqucs  du  rein.     Kev.  dc  cliir.,  1S98. 
Huber:  Biblioirraphie  d.  klin.  Hclniintholoiric,  i.,  ]MrnirIicii,  1891. 
Klemm:  Fiitleriuigsversuche  in.  Ecli,  multilocul.     Uayr.  flrzll.  Corrcspbl.,  1883. 
Lichtenbeld:  Fertilititt  u.  Sterilitat  von  Echinokokkcn  bci  Hind,  .Scliwcin,  .Schaf   \i. 

Pfcrd.    Cl)l.  f.  BaUt.,  Orig.,  xxxvi.  u.  .x.x.xvii.,  1904  (bit.). 
Madelung:  Bcitr.  z.  Ldire  von  den  Echinokokkcn,  ytuttgarl,  18H,-,. 
Mangold:  I'd).  (1.  inultiioc.  Echinococcus.    Bcrl.  klin.  Woch.,  ISS'i. 
Melnikow-Raswedenkow :  Stud,  fiber  den  Alveolancliinococciis.     ]5<ilr.  v.  ZngUr, 

iv.,  Suppih.,  Jena,  19(tl. 
Mosler:  Ueber  jVIilzeciiinococcus,  ■Wiesl)ad(fn,  1H84. 

Miiller:  Zur  Kenntn.  d.  Taenia  echinococcus.  ]\liincli.  mrd.  Woch.,  1893. 
Naunyn:  Eutwickelung  d.  Echinococcus.  Dorpal.  nied.  Ziilschr,.  IHTO. 
Neisser,  A.:  Die  Echinokokkenkrankheil.  Berlin.  IST:^.. 


732 


THE    ANIMAL    PARASITES. 


Ostertag-:  Ueb.  d.  Ecli.  imiltil.  bei  Rindeni  u.  Schweineii.     Deut.   Zeitsfiir.  f.  Tliier 

nicd.,  xvii.,  1890. 
Peiper:  Tierisclie  Parasiteu.     Ergebn.  der  allg.  Path.,  vii.,  1902  (Lit.). 
Posselt:'Die  geographisclie  Verbrritung  des  Blasenwurmleidens,  Stuttgart,  1900(Lit.). 
Riemann:  Keimzerstreuung  d.  Echinococcus.     Beitr. 

V.  Bnins,  xxiv.,  1899. 
Sommers :  Statistics  on  Echinococcus  Disease  in  the 

United  States.     N.  Y.  Med.  Journ.,  1896. 
Tschmarke:    Beitr.    z.   Histologic  des  Ecliinococcus 

niultilocularis.     Inaug.-Diss.,  Freiburg,  1891. 
Vierordt:  Abliandlung  iiber  den  multiloculilren  Echi- 
nococcus, Freiburg  1.  B.,  188(5. 
Virchow:  Verb.  d.  phys.  med.  Ges.,  vi.,  Wiirzburg, 

1855;  Vircli.  Arch.,  6  Bd.,  1854. 
Wilms:  Echinoc.  multiloc.  d.  Wirbelsiiule.     Beitr.  v. 
Bruns,  xxi.,  1898  (Lit.). 

g  194.  Bothriocephalus  iatus  (Bremser) 
or  pithead  is  tbc^  most  formidable  tapeworm 
of  man,  measuring  from  5-8  metres  in  length, 
and  consisting  of  three  thousand  to  four 
thousand  short  but  broad  segments  (Fig. 
560),  which  are  broadest  in  the  middle  region 
and  narrower  again  at  the  end.  The  length 
of  the  largest  segment  is  about  3.5  mm.,  the 
breadth  about  10-12  mm. 

The  head  (Fig.    570)  has  a  long  oval  or 
club  shape,  is  about  2.5  mm.  long  and  1  mm. 
broad.     It  is  somewhat   flattened,    and   pos- 
sesses on  each  lateral  margin  a  slit-like  de- 
pression, and  is  mounted  upon  a  filiform  neck. 
The   body   is    thin    and   flat 
like  a  ribbon,  wdth  the  exception 
of  the  central  jiarts  of  the  seg- 
ments which  project  somewhat 
outward.     At  this  spot  the  uter- 
us is  found,   in  the  shape  of  a 
single    canal,    which    forms    a 
number  of  coils  (Fig.    571,  m). 
When  the  eggs  collect  here  in 
great  numbers  the  lateral  coils 
of  the  uterus  arrange  themselves 
in  folds,  so  that  a  remarkable 
rosette-like  appearance   is  pro- 
duced.    The  sexual  openings  lie 
in  the  middle  line  of  the  ventral 
surface,    near    to    the    anterior 
border  of  the  segment,  the  fe- 
male orifice  (o)  being  close  behind  the  male  opening  (/). 

The  ovary  (g)  is  a  double  organ  which  lies  in  the  middle  layer;  the 
yolk-chambers  (/?),  on  the  other  hand,  are  located  in  the  cortical  layer. 
The  shell-gland  (A)  lies  behind  the  collecting- tube  (I)  of  the  yolk-cham- 
bers. The  testicles  consist  of  clear  vesicles  (b)  which  lie  in  the  lateral 
portions  of  the  middle  layer,  and  communicate  by  means  of  fine  canals 
(c)  with  the  vas  deferens  (d),  which  terminates  in  the  cirrus-sac  (e,  f). 
The  c(jf/fi  (Fig.  572)  are  oval,  and  are  about  0.07  mm.  long  and  0.015 
mm.  broad.  They  aie  surrounded  by  a  thin,  brown  shell,  the  anterior 
pole  of  which  forms  a  sharply  outlined  cap-like  cover. 


Fig.  ^'69.— BothriocephaJus  Iatus. 


FIG.  570. 
(After  Leuck- 


art.) 

Fig.    570. —  Head  of    Bothriocephalus  Iatus  of 
Bremser.    (After  Heller.)    Enlarged. 


i^ornHiocKiMiAMs  L.vn  s,  7;{;{ 

Tne  Both  rioecphalus  hit  us  occnvs  i-h\rl\y  in  S\\  itzcrlaiid,  in  \ho  noilli- 
>tein  parts  of  Europe,  in  Holland  and  in  Japan,  and  lives,  as  doos  tlio 


rf 


hi- 


■^-f 

^ 


Fig.  oiL— Median  portion  of  a  proglottis  of  Bof  ?iriocep7iaJws  ?rtf?(s,  si'cn  fnmi  thr  ii.ii-;ii  -uirn.'.  The 
cortical  layer  of  the  seffineiit  lias  been  removed  exwpt  a  border  on  each  si<lc,  ami  the  miililli'  lavi-r  thus  ex- 
posed. (After^riiiiiii.T.i  ,1.  Lateral  vessels:  />,  testicular  vesicles  ;  c,  trsiiciihir.aiialiciiH  :  -/.  srniiiial  duct.s; 
c,  posterior, /,  anterior  liollnw-uuiscle  apparatus  (cirrus-sac  of  vas  defeii-iisi ;  </,  uvaiv;  h.  vciik-<'li»iiihers 
lying  :a  the  coitieal  area;  i,  collecting-duct  of  yolk-stalk,  branches  of  which'  leuil  veiitrallv  to  the  yolk- 
chambers;  7c  shell-gland;  1,  beginning  of  the  uterus;  nu  loop  of  uterus  tilled  witli  eggs,  the  orillce  of 
uterus  opening  on  the  anterior  surface ;  n,  vagina ;  o,  vaginal  opening.    X  3.5. 


Taenia,  in  the  small  intestine  of  man.  According::  to  Bollinger  it  is  rather 
frequent  in  Municli.  The  first  sta.oe  of  dovelo])meiit  of  the  eggs  takes 
l)la('e  ill  water.  After  the  lapse  of  montlis  there  (le\-el(»])s  an  embryo 
(  Oncosphara)  armed  witli  six  hooklets  and  covered  wit  h  eilia'  (  I'ig.  ."i?;} ). 
This  develops,  in  some  intermediate  host  as  yet  unknown,  into  a  nieaslo 
(Pleroce)-c'oid),  which,  according  to  the 
investigations  of  Brann  in  the  Bussian 
Baltic  provinces,  seeks  out  as  second  in- 
termediate host  the  i)ike  or  tadpole,  and 
develops  in  the  muscle  or  internal  organs 
of  these  animals  into  a.  sexless  t; 


According  to  (xiassi  ai 
sle  of  Bothriocephalus 
latus  in  Italy  occurs 
in  the  pike  and  in  the 
river-perch.  In Ja])an 
it  is  found  most  fre- 
quently in  the  Ondu)- 
rlij/n  eh  us  Perriji  (  T j  i  m  a , 
Leuckart).  Zschokke 
f<»und  it  in  the  Lake 
of  Geneva  in  the  fol- 
lowing forms  of   fish: 


(1  1' 


]>e\Vi 

tlie 


Fio.  572.— Eggs  of  JiothrioccphnluM 
having  been  emptied  of  Its  yolk-cont«nts. 


""t'lii.uni 

Hi.. 


hilim.  tl ne  nt  the  right 

(.\fter  U-uckart.) 


FrG.  ")7.3.     Free  etiiliryo 
velope.     f.Xfler  l.eurkart,) 


>t  Bulhriuccphulux  Utius  with  clllal*^!  en- 


734  THE    AXI.MAL    PARASITES. 

Lota  oih/aris,  Prrcd  JiiirHitnis,  Salnio  niiihht.  E-sox  IhcIus,  Tniii<(  ruJt/di-l.s, 
and  Tniffa  lacmstris.  It  is  found  most  often  in  the  tadpole  {L<)f«  nil- 
garis)  iiud  in  the  perch  {Perca  Jinviaiilis).  Should  the  measle  y,aiu  en- 
trance, through  the  ingestion  of  the  tlsh  mentioned,  into  the  intestinal 
canal  of  man,  it  again  attains  sexual  maturity.  According  to  Brauii 
and  Paroua  the  measles  may  also  be  brought  to  development  in  both 
dogs  and  cats.  The  presence  of  Bothriocephalus  in  the  intestine  gives 
rise  to  a  gradually  increasing  antcmia,  which  resembles  pernicious 
anaemia.  The  diminution  of  the  rod  blood-cells  and  of  the  htemo- 
globin  content  of  the  blood  is  probably  due  to  the  fact  that  aftcn-  the 
death  of  the  tapeworm  poisonous  products  aiise  having  an  injurious 
action  upon  the  blood  corxjuscles. 

Bothriocephalus  cordatus  (Leuckart)  is  a  tapeworm,  of  SO-11.3  cm.  l()ll.<,^  and  has 
a  licart-shaped  head,  whose  sucking-grooves  are  flatteued.  The  breadth  of  tiie  ripe 
seiiments  is  about  7-8  mm. :  the  length,  about  3-4  mm.  In  Greenland  and  Iceland  it  is 
a  frequent  parasite  of  tlie  dog,  seal,  and  walrus,  and  is  found  occasionally  in  man.  The 
measles  likewise  occur  in  fishes. 

Bothrioi't phtihis  Mun^oni  {Cobbold)  or  liguloides  (Leuckart)  is  the  measle  (plerocercoid  i 
of  a  tapeworm  which  has  been  observed  a  few  times  (Manson,  Ijima,  Murata)  in  the 
body-tissues  and  in  the  descending  urinary  passages  or  in  the  urine.  Its  origin  is  not 
known. 

BothriocepMlus  felis,  which  occurs  in  cats,  is  very  similar  to  the  Bothriocephalus 
latus. 

BothriocepMlus  latus  occurs  also  in  dogs.  In  the  United  States  this  worm  is  found 
occasionally  in  individuals  who  have  come  from  the  various  infected  regions  of  Europe. 
In  the  mining  regions  of  Xortliern  Michigan  it  lias  been  found  a  number  of  Times  iu 
Finns. 


Literature. 

(^Bothrio('f'pJi((li(.s  Lilt  us. ) 

Bollinger:  Bothriocepli.    latus  in  Manrlaii.      Deut.    Arch.   f.    klin.    .Med.,     xxxvi., 

18«5. 
Braun:  Virch.  Arch.,  88  u.  92  Bd.;  Zur  Entwickelungsgeschichte  des  l)reiteu  Band- 

wurmes,  Wiirzburff,  1885;  Ueber  den   Zwischen^virth   des  breiteu  Bandwurmes, 

Wur/burg.  1886:  Die  thier.  Parasiten  des  Menscheu,  Wiirzburg,  1903. 
Grassi,  B.,  o^Rovilli:  Coutrib.  alia  studio  dello  sviluppo  del  Botriocefalo  larn.     Giorn. 

(IcliaK.  Accad.  di  Med.,  1887:  ref.  Cbl.  f.  Bakt.,  iii..  1888. 
Leuckart:  L.  c,  uud  Zur  Bothriocephalus-Frage.    Cbl.   f.   Bakt.  u.   Parasitcnk.,  i., 

Schaumann:  Zur  Kenntuiss  der  Bothriocephahis-Anilmie,  Berlin,  1894. 

Schaumann  u.  Tallqvist:    Blutkiirperclien   auticisende   Eiuensch.   d.   brciun    i^and- 

wurmcs.      Deut,  med.  Woch.,  1898. 
Sommer:   Tcb.  d.  Jiau  d.  geschlechtsreifen  Glicdcr  v.  15.  l.itus.  Lcii.zig.  ISTO. 
Vanlair:  ('as  de  Bothriocephalic  en  Belgique.     Bull,  ile  lAc.  Boy.  do  Bclgi(|iu'.  wiii., 

1S89. 
Wilson:     Bolhriocei)halus   latus   (Unitc.l   States).     Amcr.    Journ.    of   [Med.    Sc.    19<r2 

(Lit.). 
Zschokke:    Bothriocepli.   latus  iu  Ganf.     Cbl.    f    Bakt.,   i.,   1887;    Zwisclicnwirth  d. 

Bothr.  latus.     lb.,  iv.,  1.SS8. 


B.  Xkmatjielmixthes  (Bound  WoKMt^). 

§  l!).").  All  the  round  worms  which  occur  as  parasites  belong  to  the 
Nematoda.  They  possess  a  slender,  cylindrical,  elongated,  at  times 
lililorm  body  without  segments  or  appendages.  The  cuticle  is  thick  and 
elastic.     The  mouth  opening  is  found  at  one  extremity,  and  ts  provided 


I 


ASCAKIS     LI    MIUiMOl  DK 


7'M 


sometimes  with  soft  and  st.nu'times 
witli  liorn-Iike  lips.  The  olf.iiiialed  in- 
testine, toiiether  with  the  i)Ii;Mynx  an<l 
ehyU'-stoniaeli.  exleiids  tliron^li  tlie  I'n- 
tire  body-eavily  (Fij;'.  •^>"  t)  and  opens 
upon  the  ventral  snrfaee  a  slunt  dis- 
tance from  the  (nsnally)  awi-sliaped 
posterior  extremity.  The  sexnal  or- 
gans and  their  openings  are  also  fonnd 
on  the  ventral  surface.  The  female 
sexual  orifice  is  located  at  about  flie 
middle  of  the  body,  less  fre([Mently 
near  the  anterior  or  posteiioi'  extremity 
(Fig.  .■)74,  A,  a).  In  the  male  the  sex- 
ual opening  and  the  anus  are  located 
together  {B,  c).  The  chitinous  covei- 
ing  of  the  lower  gut  forms  in  the  male 
the  means  of  clinging  during  the  act 
of  copulatiou.  The  males  are  usually 
smaller  than  the  fenmles.  The  de- 
velopment is  direct,  and  the  metamor- 
phoses are  not  striking.  The  nema- 
todes occurring  in  man  are  in  pait 
harmless  parasites  of  the  intestine,  and 
in  part  very  dangerous,  sometimes  e\en 
fatal,  parasites  of  various  organs. 

§  !?)().  Ascaris  lumbricoides,  the 
commou  rouud-worm  (Fig.  r»74)  is  a 
light-brown  or  reddish,  cylindrical 
worm  with  tapering  ends.  The  female 
(A)  is  2.">-4()  cm.  long,  the  male  (  /> )  is 
much  smaller,  and  the  posterior  ex- 
tremity of  the  latter  is  bent  in  the 
form  of  a  hook  and  provided  with  two 
spicules  (c)  or  chitin  processes. 

The  mouth  opening  (/>)  is  sur- 
rounded by  three  muscular  lips  bearing 
fine  teeth.  The  female  sexnal  o])ening 
(A,  a)  lies  anterior  to  the  middle  of 
the  body.  The  eggs  Avhi<'h  the  ni:itui<' 
female  contains  in  enormous  nnmbeis 
possess  iu  their  fully  developed  con- 
dition a  double  sh<di  (Fig.  ■'u~))  and 
around  this  an  all)uminous  envelo])e. 
They  are  about  50-70 ,".  in  lengt  h.  Tlie 
worm  inhabits  the  entii-e  intestinal 
tract,  l)ut  most  fie<piently  the  small  in- 
testine. It  is  the  most  common  i)ar- 
asite  of  man,  and  is  found  fiecpienlly 
in  very  great  nundjers.  When  matnic 
females  are  present  the  fieces  contain 
the  eggs  in  great  numbers.  These  ai-e 
very  resistant  to  external  influences, 
for  example,  to  drying  and  freezing. 


Kl(i.     "4.  —  Axriirin    liinilirlriililiK. 

(After    IVrls.)  .1,   KiMiiulc:    If,   niulf. 

Nutiinil  Hizc.    At<i  Islhf  fwiiuU'  m-x- 

iial  orlllic ;  c,  tlii'  two  splciili-s  of  ihi-  iimlf ;  h, 

ilic  (eiilaiffctl)  (■••|ilmll'"«'n<l  wllli  llifthn-«'ll|»t. 

Fifj.  575.— Kkit  of  AxinriM  luwltrlrniilfii. 

with  sh'^ll  and  iilliuiiiinoiis  i-ovfrinjf.  (After 

Lruikart.)         :»«». 


736  THE    ANIMAL    PARASITES. 

The  eggs  require  no  intermediate  host  (Lntz,  Leiickart,  Grassi,  Ep- 
stein). Man  is  infected  by  the  ingestion  of  eggs  which  have  been 
expelled  from  the  bowel  and  have  matured  in  the  faeces.  According  to 
feeding-experiments  which  Epstein  carried  out  on  human  beings  with 
eggs  which  had  been  cultivated  in  damp  fseces  for  a  long  time,  the  round- 
worm attains  its  maturity  in  from  ten  to  twelve  weeks  after  the  ingestion 
of  the  eggs.  At  this  time  the  male  is  13-15  cm.  long,  and  the  female 
from  20-30  cm.  Their  presence  in  the  intestine  does  not  cause  any  no- 
ticeable disturbance.  Only  when  present  in  large  luimbers  do  they  some- 
limes,  especially  in  children,  cause  intestinal  catarrh,  vomiting,  nervous 
disturbances  and  convulsions.  Occasionally  the  worm  crawls  into  normal 
and  pathological  openings  in  the  wall  of  the  intestinal  canal,  and  in  this 
way  causes  trouble.  Thus,  when  it  crawls  into  the  ductus  choledochus, 
it  may  pioduce  bile-stasis.  If  it  penetrates  through  an  ulcer  into  the 
peritoneal  cavity  or  into  a  hernial  sac,  it  may  excite  inflammation  of 
the  tissues  concerned.  According  to  Leuckart  it  may  also  penetrate  the 
uninjured  intestinal  wall.  It  is  very  frequently  passed  with  the  stools 
])er  anum,  but  at  times  j^cr  os  in  vomiting.  From  the  pharynx  it  may 
wander  into  the  larynx. 

In  the  domestic  animals  ascarides  are  of  frequent  occurrence.  Ascaris  lumhr(- 
coitles  is  found  in  swine  {Ascaris  suilla)  and  in  cattle  (Ascaris  mtuli).  Ascaris  megalo- 
cephala,  a  round  worm  whose  female  is  18-37  cm.  long,  is  a  common  parasite  of  the 
horse  and  donkey.  Ascaris  mystax,  whose  female  reaches  a  length  of  13  cm.,  is  found 
frequently  in  dogs  and  cats,  and  has  also  been  observed  in  man.  Various  species,  des- 
ignated as  Ileterakis,  occur  in  birds.  lieterakis  maculosa,  the  round  worm  of  pigeons, 
may  cause  the  death  of  the  pigeon  when  occurring  in  large  numbers  within  its  intestine. 


Literature. 

(Ascaris  Liimbricoides.) 

Epstein:  Uebertragung  des  Spulwurms.     Jahrb.  f.  Kinderheilk.,  33  Bd.,  1892. 
Grassi:  Intorno  all'  Ascaris  lumbricoides.     Gazz.  degli  Ospetali,  ii.,  1881,  u.  Cbl.  f. 

Bakt.,  iii.,  1888;  Trichocephalus- und  Ascarisentwickelung.     Ibid.,  i.,  1887. 
Huber:  Bibliographie  der  klin.  Helminthologie,  Miinchen,  1893. 
Kitt:  Lelirb.  d.  path.-anat.  Diagnostik,  ii.,  Stuttgart,  1895. 
Leuckart:  Uebergangsweise  des  Ascaris  lumljricoides.     Cbl.  f.  Bakt.,  ii.,  1887. 
Lutz:   Zur  Frage  der  Invasion  von  Taenia  elliptica  u.  Ascaris  lumbricoides.     Cbl.  f. 

Bakt.,  ii.,  1887;  Uebertragung  des  menschliclion  Spulwurms.     lb.,  iii.,  1888. 
Peiper:  VhuTisclic  Pamsitcn.     Ergebn.  d.  allg.  Path.,  iii.,  1897,  u.  vii.,  1903  (Lit.). 
Salty kow:  Ascaridosis  hepatis.     Zeitschr.  f.  Heilk.,  xxi.,  1900. 

§  197.  Oxyuris  vermicularis,  mcJ-tan,  j>/>»ro/w,  or  threadworm  is  a 
small  round  worm  (Fig.  576"),  the  female  being  about  10  mm.  long  (a,  b) 
and  pointed  at  the  caudal  extremity  like  an  awl,  while  the  male  is  about 
4  mm.  long  (r)  with  a  blunt  posterior  end,  the  anus  being  provided  with 
a  spiculum. 

The  eggs  (577,  o),  which  the  body  of  the  female  often  contains  in 
very  great  numbers,  are  50  //  long  and  24  /j.  broad,  have  a  flat  and  a 
curved  surface,  and  a  shell  which  is  covered  by  a  thin  albuminous  layer. 
Oxyuris  vermicularis  inhabits  the  large  intestine  and  the  lower  jiortion  of 
the  small  int(>stine.  According  to  Zenker  and  Heller  only  the  impreg- 
nated mature  females  are  found  in  the  large  intestine,  the  young  individ- 
uals and  the  males  remain  in  the  small  intestine.  They  occur  very  fre- 
quently in  larger  or  smaller  numbers.  At  night  they  often  wander  from 
the  rectum  over  the  anal  region,  and  may  enter  the  vagina ;  they  excite 


ANCIl  'I  l.osiOM  A, 


73; 


itcliinj;-  of  tlie  affected  \r.u\s.  In  Hi,' 
pelvic  peritoneuiu  encapsulated  worms  (u- 
("oo-s  have  been  observed  a  munbcr  of  t  inu-s. 
It  has  not  vet  been  d«'teniiine<l  w  lid  her 
they  eaii  i)eiietrate  tin-  intestinal  wM 
(Vuillcmin).  Wau'ener  fonnd  dcail  and 
calcilied  uoinis  in  the  snl»niuc()s;i  of  the 
intestine. 

For  the  development  of  the  cj^j^s  (I'^iif. 
r)77,  a-e),  it  is  necessary  after  their  expul- 
sion Avitli  the  f.Tces  that  they  aj^ain  be 
taken  into  the  stomach  of  man  or  beast. 
It  is  very  jirobable  that  the  ori<;inal  lu»st 
may  again  infect  himself  Avith  oxyuris, 
in  that,  for  example,  the  eggs  becom- 
ing attached  to  his  finger  dui-ing  the 
act  of  scratching  may  latei-  get  into  his 
mouth. 

tire  very  resistant   to  drying, 
may  he  widely  scat- 
tered. 

Literature. 

(O.n/iiri.s.) 

Heller:  Oxvuris  vermicularis.      Ilnmll).   v.   Ziem- 

ssen.  vi'i.;    D.  A.  f.  klin.  Med.,  77  Bd.,  ]9().^ 
Eolb:  Oxyuris  vermic.    im  Cavum  Dou<rlasi.     ('l)I. 

f.  B.,  brig.,  xxxi.,  1902. 
Morro:  Cisti  imp.  sulla  salpingo  coiiten.    iiova  <li 

Ox.  V.     A.  per  le  Sc.  Med.,  xxv.,  190:;. 
Schneider:  Ox.  verm,  im  Beckenperitonoiim  eiii- 

gekapselt.     Cbl.  f.  B..  Orig..  xx-xvi.,  1904. 
Vmllemin:  Penetr.  du  fern.  d'Ox.  atrav.  le.s  parois 

de  I'intestin.     C.  f.  B.,  Orig.,  xxxii.,  1902. 
Wagener:  Oxyuris  vermic.  in  d.  Darmwand.     I).  A.  f.  klin 


The  egg> 
and  in  tliis  conditi 


Fio.  .^.76.  —Oriiurh  viriiiliuhiih. 
a.  Sexually  iiiaiiirc  f»;malt»;  I,,  femah- 
full  of  <-(r>rs;  r,  male.  (After  Meller.) 
X  10. 

,  SI    M..    Kill  I. 


4;  19S.  Anchylostoma  duodenale  {Dorlniiliis  (ImulrnnHs,  uv  Slnni;iiiliis 
ihiodrnalix,  <^»r  Vnciiiaria  (hiodctid/is,  also  CuriiKditi  ^Inicrifiiiiti  \StHts]), 
Hook-Morm,  is  a.  small  Avorm  belonging  to  the  family  <d'  Slnmifi/liths, 
which  inhabits  the  ni)per  i)art  of  the  small  intestine  (Fig.  .".7Sj.  The 
cylindrical  body  of  the  female  is5-1S  jum.  long,  that  of  the  male  C  lo 
mm.  The  cephalic  end  (Fig.  57?))  is  cnrve<l  towaid  the  dor.sal  siirl'aec, 
and  possesses  a  bellied  month-ca])siile  (d).  Jl  is  almo.st  completely 
divided  dorsally,  and  the  cleft  is  covered  by  two  chitinotis  lamelhe.  <  )ii 
the  ventral  border  there  arc  four  incurving  teeth  (/>).  on 
border  two  teeth  Avhich  are  perpendicularly  i)laced  (/•_).  all 
together  by  chitinous  band.s. 

The  male  is  provided  at  its  caudal  extremity  w  iih  a  llin 
(Fig.   578,    /)  and  two  thin,   tishbone-like  si)icules  (;/;.      In 
the  post eiior  end  is  pointed,  and  bears  an  awl-shaped 
valies  posterior  to  the  body  centic.     The  oval  eggs  (l-'ig 


the    .lorswl 
being   held 


Inld     l.lll-;l 
the    r.-m:il.- 
j>ilie;    1  he    \  III 
rtSU)  :iie  It   t;7 


/I  long,  23-40  /J.  broad.  They  undergo  the  lir.st  stages  of  cleavage  in  Hm 
human  intestine  (a-d),  develop  further  in  muddy  water  (r,/).  aii<!  ma> 
then,  if  brought  into  the  human  intestinal  tract,  develop  again  into  s.\ 
ually  mature'animals.  \\'ith  its  tc<-lh  the  worm  works  its  wav  into  ih* 
47 


738 


THE    ANIMAL    PARASITES. 


mucous  membrane  us  far  as  the  submucosa,  and  sucks  itself  full  of  blood 
Its  point  of  attack  is  distinguishable  later  by  a  small  ecchymosis  in  the 
middle  of  which  there  is  a  white  spot  with  a  central  perforation.     Oc- 
casionally there  are  found  iu  the  intestinal  mucosa  small  cavities  filled 
with  blood,  withiu  each  of  which  there  lies  a  coiled-up  worm.     The  para- 


FiG.  577.— Effgs  of  Oxyuris  reniiin 
Heller.)    o,  h,  c.  Segmentation  of  yolk  ; 


litferent  stages 
-shaped  embiyo ; 


)f  development.     CAftei 
(',  worm-shaped  embryo. 


sites,  when  present  in  large  numbers,  cause  a  continuous  and  serious  loss 
of  blood,  which  may  lead  to  the  most  severe  forms  of  anaunia  {Egyptian 
chlorosis),  but  they  are  not  infrequently  found  in  individuals  who 
present  no  symptoms  of  disease.  The  parasite  is  very  common  in  the 
tropics,  and  also  in  Japan.  According  to  Griesinger  and  Bilharz  about 
one-quarter  of  the  native  Egyptians  suffer  from  this  disease.  The 
parasite  w^as  very  often  observed  in  the  workmen  engaged  in  the  Saint 
Gotthard  tunnel.  According  to  Menche  and  Leichtenstern  the  brick- 
fields of  the  Ehine  provinces  are  to  a  great  extent  infected  with  anchy- 
lostoma  (brick-burner's  anaemia). 

In  1903  the  worm  was  distributed  to  an  extraordinary  degree  through- 
out the  mines  of  the  mining  district  of  Dortmund,  so  that  in  the  autumn 
of  that  year  over  seventeen  hundred  individuals  infected  with  the  worm 
-were  found. 

The  infection  takes  place  chiefly  through  larvtB  ingested  with  the 
drinking-water  and  food.  According  to  the  investigations  of  Looss  and 
Schaudinn,  the  larvje  may  penetrate  through  the  skin  into  the  veins, 
thence  are  carried  into  the  lungs,  whence  they  wander  through  the  bron- 
chi, trachea,  and  larynx  into  the  intestinal  tract.  In  experiments  made 
upon  apes  the  larvte  may  be  found  in  the  intestine  within  twenty-four 
hours. 

According  to  Stiles  (1902),  the  hookwornniisease  of  the  American  contiiieut  is  due 
to  a  distinct  species  from  that  found  in  Europe.  He  distinguishes  them  as  the  Old- 
World  hookworm  and  the  New-World  hookworm  {Necator  americanus  or  Uncinaria 
americana).  The  latter  form  is  prevalent  throughout  the  Southern  United  States  as 
far  north  as  the  Potomac  River,  and  in  the  West  Indies,  and  has  also  been  found  in 
Italy,  Africa,  China,  and  the  Philippines.  It  is  a  cylindrical  worm  7-11  mm.  long, 
with  a  dorsal  and  ventral  pair  of  lijjs,  a  prominent  dorsomedian  buccal  tooth,  and  four 
buccal  lancets.  In  the  male  the  dorsal  ray  of  the  bursa  divides  at  the  base  and  each 
branch  possesses  two  tips.  In  the  female  the  vulva  is  in  the  anterior  half  of  the  body. 
The  eggs  have  more  sharply  rounded  poles  than  those  of  the  Old-World  worm.  It  is 
estimated  that  abotit  ninety  per  cent  of  the  rural  population  of  Porto  Eico  is  infected  with 
this  parasite,  and  in  some  ])arts  of  Florida  a  similar  degree  of  infection  is  reported. 
According  to  Stiles,  the  piney-wood  and  sandy-soil  portions  of  the  South  are  especially 
wgions  of  infection.     In  these  regions  "  ground  itch  "  is  of  common  occurrence,  and  is 


AXCIIVI.OS'IOM  A. 


I)elievetl  now  to  he  iliie  to  the  Dcni't riti,>i.  ;.,»,«  .1       i  •       <•    i      i 

■^"-"^ "» -  -i^-  »>"Miu;:^;:"i;;':;r!^„;t:,s^;!:;;;;;;;";,;;;,.;;;;;,'';::t:::;;;:;i 


z:r;x     .-::» 


^ 


<^ 


Fig.  57K. 

ft,asopha^us:  c,  intestine:  c?,  anal-glands  ;  e,  cervical  glands:   r.  skin  ;  f//n.iis.l/^l»v"   :  nir.^x"n^ 

dhwf^^'W^'''"*'*''^''^'*.?'"""'^  '■•"''^°^  ^'^«  ""'^•■1:  ''  testicular  canal;  m,  seminal  vi.«k-le:  ».,  .-J.  ru  atorv 
duct;  o,  groove  of  latter;  p,  penis;  7,  penis  sheath.     X  18.  .  ",  <  ja.  maiorv 

«»  „^'?-  5"0.-Cephalic  end  of  .  1  i,rlnih,^l,,i,i<i  ,Iin„'Ui,-ih-.    CAfter  Scliulth.-ss.)    n,  Moiilh-capsiil.- :  /..  ti-ell 

SLTf^^^^  border;  c,  tewh  of    ,|o,sal  iH.nl.T;  -/.  1 ith  cavity;  e,  skin  protnlM-niiic  on  vcnin.l  side  ..f 

Head;  /,  muscular  layer;  </.  iloi.ni  l^oonc;  //,  (rsopiiaL'us.      x  100. 

•.„„^IG.  580.— Eggs  of  Anclii/histoina  dwntaialc.     (After  Perroncito  and  S<-hultliess.)    o-<1.  Different 
Stages  of  segmentation ;  e,  /,  eggs  with  embryos.    X  300. 

appetite  ("clay-eaters"),  pain  and  tenderness  in  tlie  epi^'aMriuni,  tlciayed  |iiilKTt\ 
mental  lassitude,  etc.  The  "  cotton-mill  ana-mia  "  of  the  Sontli  is  dur  iJ,  .1  nirMJ.Tair 
degree  of  hookworm  infection.     The  economic  importance  of  uncinariasis  in  .\inericii 


740  THE    ANIMAL    PARASITES. 

is  very  great.  It  is  estimated  that  thirty  per  cent  of  all  deaths  in  Porto  Rico  are  tlic 
result  of  hookworm  infection.  According  to  Stiles,  this  infection  is  chiefly  responsible 
for  the  inferior  mental  and  physical  condition  of  the  poorer  classes  of  whites  in  certain 
parts  of  the  .Southern  States. 

Eustrongylus  gigas,  a  palisade-worm  of  red  color,  whose  female  reaches  a  length 
of  1  metre,  is  a  very  rare  parasite,  which  has  been  observed  only  a  few  times  in  the  kid 
ney-pelvis  of  man.  It  occurs  verj'  frequently  in  dogs.  It  possesses  a  mouth-opening 
with  .six  papillae ;  the  male  has  on  its  posterior  extremity  a  bursa  with  a  single  spicii- 
lum.  The  eggs  are  ov.d.  0.06  nmi.  long,  and  provided  with  a  rough  albuminous 
capsule. 

Strongylus  longevaginatus,  a  thread-like,  white  worm,  SO  nun.  hmg,  was  once 
observed  in  the  lung  of  a  boy. 

In  the  domestic  animals  Strongylides  occur  in  much  greater  numbers  than  in  man, 
and  are  in  part  inhal)itants  of  the  intestine,  and  in  part  of  the  lungs  {MiUler,  "Die 
Nematoden  der  Saugcthicrlungen,"  Dent.  Z<Hschr.f.  Thiermed.,  xv.,  1886). 

Dochmius  trigoiKin  jihidus  and  Ihiclniiins  sti  nocephalus  occur  in  the  intestine  of  dogs, 
and  give  rise  to  aiiaiuia  similar  tn  ihat  lunduccd  by  the  Anchylostoma  in  man. 

Strongylus  arntnlns  is  a  common  jiarasite  of  the  horse,  which  enters  the  inti'stinal 
tract  as  an  embryo,  bores  into  the  intestinal  wall  {Olt),  thence  into  the  liver,  by  way  of 
the  portal  vein,  and  further  into  the  lungs  and  the  organs  of  the  major  circulation. 
Following  this  migration,  it  may  develop  in  the  most  diverse  organs  and  cause  the 
formation  of  fibrous  nodules,  which  become  calcified  after  the  death  of  the  parasite 
enclosed  in  them.  In  the  intestinal  wall  it  may  develop  after  direct  migration  or  after 
embolic  lodgment  in  the  part,  and  leads  to  the  formation  of  cavities,  from  which  ii 
again  breaks  through  into  the  intestinal  lumen.  In  the  mesenteric  arteries  it  attains 
sexual  maturity,  and  causes  thrombosis  and  the  formation  of  aneurisms.  The  male  of 
the  mature  worm  is  20-30  mm.  long ;  the  female,  20-55  mm. 

Strongylus  tetracantJius,  which  inhabits  the  large  intestine  of  the  horse,  causes  a 
haemorrhagie  enteritis  when  present  in  large  numbers. 

StrongiiliiK  pii nido.vus  is  an  extremely  common  parasite  of  the  lungs  of  hogs. 
Strongylus  rnjiiUiiris,  Str.  commut<(tus,  and  Sir.  filaria  are  frequent  parasites  of  tlie 
lungs  of  goats  and  sheep,  and  different  species  may  be  present  in  the  same  lung  at  one 
time  (Schlcgcl,  "  Die  durch  Strong,  capillaris  verursachte  Lungenwurmseuche  der  Ziegc. " 
Arch.  f.  wiss.  TMerJieil.,  25  Bd.,  1899).  The  latter  causes  in  sheep  a  bronchitis  and 
nodular  proliferating  pulmonary  inflammations;  through  the  swallowing  of  many 
embryos  inllammations  of  the  intestine  may  also  be  jinidueed. 

Strongylus  vufesccns  and  Str.  par<idi'.r'i/x,  2\( iiiKlmdiii u,  ^nis  jiidnionalis  {Lydtin),  or 
Pticudalius  ocix  juihiiniiiilis  (Kocli)  vlvh  also  inhabitants  of  the  lungs  of  sliee]\  tlie  last 
named  causing  a  pseudotuberculosis.  Str.  C(t/,niii/ti/t//s  and  Str.  inisilhis  uvvxw  in  tlir 
lungs  of  the  hare  and  labbit;  Str.  syngamuK  and  hronchidlns  in  tin-  trachea  of  biids;  and 
excite  inflammations.  Str.  micrurus  (Sirose,  "Bau  von  Strongjdus  micrurus,"  Dct/. 
Zeitsckr.  f.  Thiermed.,  xviii.,  1892)  occurs  in  cows  and  calves,  in  arterial  aneurisms  as 
well  as  in  the  respirator}^  passages. 

Strongylus  pusillus  causes  in  cats  a  pulmonarj-  disease  resembling  tubercidosis 
(.Jeatinaiire,  "  Ueber  die  hist.  Verand.  der  Lunge  bei  der  verminosen  Pneumonic  der  Katze 
imd  des  Hasen,"  Inaug. -Diss. ,  Freiburg,  1900).  Syngamus  trachealis  (Klee,  "Der  ge 
paarte  Luftrohrenwurm  des  GeHiigels,"  Beut.  Thicrdrztl.  Wochcnschr.,  1899)  is  a  dan- 
gerous parasite  of  birds,  particularly  of  pheasants,  in  the  trachea  of  which  it  appear.- 
in  great  numbers,  and  attaches  itself  to  the  mucous  membrane.  It  is  easily  recognized 
by  its  red  color.  Similar  to  the  last-named  is  Syngamvs  hronchialis,  which  has  been 
observed  a  few  times  in  geese  and  ducks. 

Literature. 

(Aiir/iglo.stonia  <(nd  ^Iroiufijlus.) 

Baumler:  Anchylostomiasis.     Correspbl.  f.  Schweizer  Aerzte,  isyi,  ISS."). 
Bugnion:  Anchylostome  duodenal  et  anemie  du  St.  Gotthard.     Ww.  med.  de  la  Suisse 

rom.^i.,  1881. 
Ernst:  Einige  Fiille  von  Anchylostomiasis  mit  Sectionsbefuud.     Dent.    med.   AVoch., 

1888. 
Huber:  Bibliograiihie  d.  klin.  Helminthologie,  Miinchen,  1893. 
Iberer:  .Vnkylostomagefahr  in  Kohlengruben.     Miinch.  med.  Woch.,  1903. 
Kasewiirm  u.  Steinbruck;    Nematoden.   Ergebn.  d.  a.  Path.,  viii.,  Wiesb.,  1904  (Lit.). 
Kitt:  Lehrl).  d.  path.-anat.  Diagnostik.  ii..  Stuttgart,  1895. 
Leichtenstern:  Anchylo.stoma.     ("bl.  f.  klin.  Med.,  1885,  1886;    Deut.  med.  Woch., 

ISS.-,,  JSSC,  1887,  1888;    Wien.  klin.  Rundschau,  1898. 


I 


AXGllLH  LA    IXTKsriN  AM; 


isor,,  x\i, 

,     C.  f.  B. 


IS!  17 

xxix. 


Looss:  T.rhcnstieschiclUo  d.  Aiicliylostoiimni.  CM.  f  li;ikt.,  \x 
xxiv.,  189S;  Eiinvaiuleruns  ties  AiikvlosiDnia  mmi  dn-  llaiif  a 
1901,  u.  Orifi.  xxxiii.,  19(W. 

liUtz:  Saniiiil.  klin.  Vortr.  v.  Volkmaiiii.  Xos.  •_'.").'>,  J.Vi.  L'(»."). 

Menche:  Ancliylostoiniasis.     Zcitsdir.  f.  kliii.  Med.,  vi. 

Olt:   Waiulorunseu  des  Strongyliis  arniatus.     t'l)l.  f.  Hakt..  xxix..   litOl 

Peiper:  Tierische  Parasiten.     Ergebn.  d.  allg.  Path.,  vii.,   I'lOi'  {\At.). 

Peri-oncito:  Arch.  p.  Ic  8c.  Mod.,  v.,  Torino,  ISSl;    .Vrcli.  ilal.  dc  liiol., 

Prowe:  Aiichylostoiniasis  in  Central  America.     Vircli.  Arcli.,  1,')7  lid.,  IS'.dl. 

Schaudinn:  Einwand.  d.  Ankylostoma  v.  d.  Haul  aiis.      I),  nii-d.  Woch..  UK) I 

Schulthess:  Beitrage  z.  Anat.  des  Anchylcstoma.  Zeitsclir.  f.  wi.ss.  Zool.,  x 
iss-i. 

Sonderegger:  Acliylostoma  duodenale.     ('orro.sphl.  f.  Schwcuzcr  .Vcrzle,  l.SSd. 

Stiles:  Prevalence  and  CJeographic  Distribution  of  Hookworm  Disease  (I'ncinari 
.Vnchylostomiasis)  in  the  I'nited  States.  Bull,  of  Hyg.  I,ab.,  Pul).  Healt 
Marine-Hospital  Service  of  the  I'nited  States,  liHKi;   Osier's  Mod(>rn  .Me«Iicine, 

Tenholdt:  Die  Ankylostomiasisfrage.     C.  f.  B.,  Ref.,  xxxiv..   I'll) I. 

Ward:  Xematoda.     Ref.  Hdb.  of  Med.  Sc,  2d  ed.,  vol.  vi. 

Zinn  u.  Jacoby:  Anchylostomimi  duodenale,  Leipzig,  1898  (Lit.). 

§  IIM).    Anguillula  intestinalis  (Fij;.    581)  is  a  worm  of  l*.L'.".  laiii. 
leugtb,  which  is  found  in  the  intestine,  particularly  in  tlic  tropics,  iiiid  in 


iii.,  lNs;j. 


;i.>;is  or 
h  .-inrl 
vol.  L 


Anoulllida  intcatindlis. 
(After  Braun.) 


Fir;.  5M2,— Ft'iimlf  <>f  -1  imiiilhila  htfrrninli 
.■L'L'sMiKl  fiiitiryos.    i.KUvr  |Vrr.>iii-li<... 


Italy,  and  has  been  occa-sioually  observed  in  Swit/.rrl: 
gium,  andHoHand  (probably  transported  from  Jfal.\  < 
ditions  as  the  Anchvlostonia  duodenale.     .Vccortlin.^- 


d.  (. 


i-nu:in 
isiliiil 
(disci' 


.    I'.rl- 

ir  ri»n- 


742  IJIE    ANIMAL    PARASITES. 

of  Leuckai't,  Golgi,  Grassi,  Leiclitensteni,  Ziiiii  and  others,  the  Aug k ill ida 
intestlnalis  is  a  hermaphrodite,  the  eggs  of  ^  hich  de\'elop  even  iu  the 
intestine  to  embryos  of  0.2  mm.  in  length;  and  in  the  presence  iu  the 
intestine  of  numerous  parent- worms  are  found  in  the  f seces  in  great  num- 
bers. In  the  stools  they  become  changed  within  about  twelve  hours  into 
filaria-like  larvae,  which,  when  gaining  entrance  into  the  human  intestine, 
again  grow  into  parasitic  anguillulte,  which  are  again  able  to  produce 
eggs  capable  of  development.  In  addition  there  also  occurs  a  develop- 
ment with  an  intermediate  sexual  generation,  a  heterogony. 

In  the  event  of  a  sexual  development  the  embryos  grow  outside  of  the 
body  in  about  three  days  into  sexually  mature  animals  (female  1.2  mm. 
long,  male  0.88  mm.)  which  are  known  as  Anguillula  or  Bhabditis  sterco- 
rcdis  (Fig.  582),  and  were  formerly  regarded  as  a  separate  species.  The 
embryos  of  the  separate  sexual  individuals  develop  into  filaria-like  larvae, 
which,  entering  the  intestine  of  man,  again  grow  into  parasitic  anguil- 
lulse. 

According  to  Leichtenstern  and  Zinn  the  filaria-like  larvte  of  the 
direct  development  are  more  resistant  than  those  of  the  sexual.  The 
sexual  mode  of  multiplication  occurs  i)articularly  in  the  anguillula,  com- 
ing from  the  trojncs,  while  in  the  indigenous  form  (brick-laborers  of 
Germany,  Belgium,  Holland)  the  direct  metamorphosis  predominates. 
Leichtenstern  has  explaiiied  this  by  the  assumption  that  the  tropical 
anguiUula  after  its  transportation  into  a  temperate  zone  has  adapted 
itself  to  the  less  favorable  climatic  conditions  of  the  latter  in  such  a 
manner  that  the  anguillula  of  the  temperate  zone  favors  more  tlie  much 
simpler  mode  of  development  which  is  the  more  indejjendent  of  the 
climate — namely,  tlie  direct  transformation  of  the  embryo  into  the  filaria- 
shaped  lar-v^e,  Miiicli  in  turn  grow  directly  into  parasitic  anguillnlte. 

According  to  the  statements  of  various  authors  Anguillula  stercoralis 
when  j)resent  in  large  numbers  causes  diarrhoea.  According  to  I^ormand, 
Grassi,  Golgi,  Leichtenstern,  and  others,  the  worms  are  found  chiefly  in 
the  upper  parts  of  the  small  intestine.  According  to  Leichtenstern  and 
Askauazy  the  mature  animals  and  the  larvte  penetrate  not  only  into  the 
crjT^^ts  of  Lieberkiihn,  but  also  into  their  epithelium  and  into  the  con- 
nective tissue  of  the  mucosa,  and  in  individual  cases  may  break  through 
the  Jiiuscularis  mucosae.  The  mother  animals  lay  their  eggs  in  the  intes- 
tinal crypts.  Tlie  embryos  when  hatched  out  wander  out  into  the  intes- 
tine. 

Literature. 

{AnyuiUida  Stercoralis  and  Intestinal  is.) 

Askanazy :  Invasion  d.  Ang.  intestinalis  in  die  Darmwand.  Cl)l.  f.  Bal<t.,  xxvii.,  1900. 
Golgi  e  Monti:  Sulla  storia  naturale  delle  cosl  dette  anguillulc  stercorali  e  iutt'stinali. 

Arcii.  per  le  Sc.  Med.,  x.,  1886. 
Grassi  e  Perona:  Arcli.  per  le  Sc.  Med.,  xiii.,  1889. 
Grassi  e  Segre:  Nuovo  osserva/.ioni  suU'  eterogenia  del  Eliabdonema  (Anguillula)  in- 

tcstiiiale.     Rendic.  della  K.  Aeead.  dei  Lincei,  1887,  ref.  Cbl.  f.  Bakt.,  li.,  1887. 
Huber:   P.ibilogr.  d.  klin.  Helmintlioh.gie,  Suppl.,  Jena,  1898. 

V.  Karlow:  Auguill.  intest.  als  Ur.saciie  blutiger  Diarrhoe.  C.  f.  B.,  Grig.,  xxxi.,  1902. 
Leichtenstern:" Aug.  intestinalis.     Dcut.   med.   Woch.,    1898;  Cbl.    f.   Bakt.,    xxv., 

1S99. 
Normand:  Du  role  etiologique  de  I'anguillule.     Arch,  de  med.,  1878. 
Orley:  Die  Uliabditiden  und  ihre  mcdicinische  Bedeutung,  Berlin,  1886. 
Pappenheim  \i.  Braun:  Ana',  intest.  in  Ostpreussen.     Cbl.  f.  Bakt.,  xxvi.,  1S99. 
Peiper:  Tieriselie  Parasiten.  ^  Ergebn.  d.  allg.  Path.,  vii.,  1903  (Lit.). 


TRICHINA. 


»;; 


Perroncito:  Airh.  p.  k'  iSc .  :Mi'd.,  v.,  1881:  Aicli.  ilal.  dc  hiul..  ii.  u.  iii.  :  Ann.  K.    \.  . 

Ciid.  (li  Agricoltum  di  Torino,  xiii. ;  Jouin.  dc  I'anal.  <t  dchi  pliys.,  wiii. 
Teissier:  Auguilhile  stercorale.     Arch,  di- ini'd.  cxp..  18<r». 
Thayer:  On  the  Occurrence  of  Stronirvloidcs  ]nlr-.liMalis  in  tlic  I'ldtcd  Stales.  .It. urn 

ofExi>.  Med.,  1!H)1. 
Zinn:   Uetier  Ani;uillula  intestinalis.     Clil.  f.  liakl. .  .\  \  vi..    IsKit. 


§200.     Tricocephalus   dispar    {'rric/iini 

is  a  coiunioii    ami   relatively   liarnilcss  jcu 
Askana/.v   it    siu-l 


the    caH'Uin    and    llu 
found  also  in  the  d( 


Iriflnniii).     I  he     ir/iijiinniii, 
Utc,    thoii-li    jicconlinj;    to 
blood    li-oni    the    intestinal    nnicos;i.       it     inhaliits 
■    neiiihhorinii'    poitions    of   the    intestine.       Jl     is 
niestic  animals.     The  male  and  female  are  about 
l-.-)  em.  in  length  (Fi^^  .~..s:J).     Tin- 
anlfiioi-   body-half  (a,    h)   is    xciy 
Ihiii,     thi-ead-like;     the     |M.sl,Ti<.V 
which  beats  the  sexual  of^iatis  ( /",  //. 
/,  ».  }>),  is  mtteh  thiekef,    iti  the  fe- 
male (/;>    e\]iti(ltical,    atid   iti    thr 
male  (A)    f.'.lh-d   up    and    piux  i.|..l 
%vitli  a  spieulitm  (//). 

The  eiiji'S  {Fh^.  rtSl)  are  an  el- 
oti.i>ated  oval,  50  ."  loitj;,  and  po.ssi'ss 
a  tliiek  bfown  shell,  whicii  shows 
at  both  jxdes  a  i)e,u-shai)ed.  irlassy 
swell  iiiii'. 

The  lifst  sta<;e  of  the  (lr\cl..|.- 
tiient  of  the  eud)fy()s  takes  place  in 
water  and  iti  moist  eartii.  It  ad- 
Nances  sh)wly,  even  in  summer 
lasting  fotif  to  five  months,  atid  in 
the  colder  months  of  the  >('ar  much 
longer.  The  eggs  are  very  resist- 
ant to  cold  atid  drying.  (  For  tlie 
literature  see  Jfiihrr,  '•  IJibliogra- 
])liie  (ier  klin.  Helmintliologie," 
Miinehett,  ISO;},  p.  'Jl.'>;  Ashiuazy, 
••  Der  I'eitsehenwttrm,"  Ihut.  Arch. 
f.  hUn.  Mrd.,  Tu  J  Id.,  1S!MJ;  llriur, 
••  .Vnatomie  d.  Trieoccphalits,  "  Chi. 
/.  liaht,  xxviii,  HMHti. 

s<  201.  Trichina  spiralis  occitts 
ill  two  lorms— the  trichina  «d"  lite 
intestine  and  the  trichina  of  tlie 
mtiseles. 

The  intestinal  trichina  (  Fig. 
585)  is  the  sexually  mature  form,  and  is  a  small,  white,  iiair  like  worm 
scarcely  visible  to  the  naked  eye.  The  female  (A)  is  ;{  mm.  long,  Hie 
male  (B)  is  much  smaller.  The  posterior  part  of  lh<'  l)ody  is  elongated 
in  both  sexes,  and  in  the  male  (B)  is  provi(h'd  on  the  dorsal  half  with 
two  conical  terminal  pegs,  Avhieli  are  directed  toward  the  belly  ami 
are  separated  from  each  other  by'  four  knob  like  papilla-.  Instead 
of  a  spiculum  the  muscular  cloaca  is  ])rot  rttded  (.iit  w:it(l  dtiting  eo|)U- 
lation. 

The  intestinal  canal  begins  with  a  itiuscitlar  month,  which  becoming 
wider  passes  into  the  (esophagus,  which  thndighonl  its  eiilit*' length  is  .stir 
rounded  by  the  so-called  cell -body— that  is,  by  rows  of  large  <-ells.  The 
stomach,  which  follows  the  (esoidiagus,  is  a  flask  sha].ed  dilatation  of  the 


(Afl< 


Fig.  n&i.—Tricncephalim  rtisy 
KucliPnmeistPr  and  Ziini.)  ^1,  Male:  7?,  caiiil; 
HDd  of  femiile  ;  n,  rephalic  ciul ;  ?>,  anterior  itnrliuii 
of  bodv  with  (I'siipha^'us  ;  <■,  stoinai'h  ;  (I,  iiilfstino  : 
<•.  cloaca  ;  f.  seminal  duct  ;  (/,  i)enis  ;  1.  Iiell-sliaped 
penis-slieatli.  with  end  of  i«'iiis  :  w.  intestine  of  the 
female;    (i,  anus;    <>,  titenis;    ji,  va.ginat  openintr. 

y  9. 

i7»s  ilisixii:     lAfter 


744 


THE    ANIMAL    PARASITES. 


iiitestiue,  and  is  lined  with  liiiely  .uraimlar  cells.  The  sloiiiacli  passes 
without  any  essential  change  of  structure  into  the  intestine,  wliich  iu  the 
male  unites  with  the  seminal  duct  at  the  posterior  end  to  form  the  cloaca. 

The  testicles  consist  of  a  pouch,  which  begins  near  the  caudal  end  as 
a  blind  sac,  proceeds  as  far  forward  as  the  cell- 
bodies,  and  bending  there,   passes  over  into  the 
seminal  duct. 

The  sexual  organs  of  the  female  (A)  consist 
of  a  single  ovary,  a  uterus  and  a  vagina,  which 
opens  externally  at  the  junction  of  the  first  and 
second  quarters.  The  ovary  likewise  forms  a 
pouch  lying  close  to  the  posterit)r  end  of  the 
body,  iu  which  the  rouud  eggs  develop.  The 
pouch  passes  anteriorly  into  the  sac-shaped  uterus. 

The  eggs  develop  Avitliin  the  uterus  into  em- 
bryos which  are  set  free  at  l)irth. 

The  muscle=trichina  (Fig.  586)  is  a  wonn 
0.7-1  mm.  in  length,  which  lives  in  the  muscles 
of  the  body.  It  is  usually  rolled  into  a  sj)iral 
and  lies  iu  a  capsule,  which  occasionally  contains 
lime-salts.  Betweeu  the  coils  of  the  worm  there 
is  a  finely  granular  mass. 

A  single  capsule  may  contain  three  to  five 
trichinae. 

If  a  piece  of  muscle  containing  living  tri- 
chiuge  is  taken  into  the  stomach  of  a  host— for 
example,  man — the  capsule  is  dissolved  and  the 
trichinae  are  set  free.  In  the  intestinal  canal  they 
attain  sexual  maturity  within  two  and  a  half  days, 
when  copulation  takes  place.  On  the  seventh  day 
after  the  ingestion  of  muscle  trichinse  the  birth 
of  embryos  begins,  which  continues  some  time, 
even  for  weeks.  A  single  female  trichina  may 
bear  from  one  thousand  to  thirteen  hundred 
young.  According  to  Pagenstecher,  Chatin,  Cer- 
fontaine,  and  Askanazy,  the  female  trichinae  pen- 
etrate into  the  intestinal  villi  and  deposit  the 
embryos  in  the  chyle-vessels,  whence  their  migra- 
tion begins.  To  what  extent  they  are  swept  along 
passively  by  the  lymph,  or  to  what  extent  active 
migration  is  concerned  in  their  spreading,  is  a 
dilficult  matter  to  determine.  When  ariiving  in 
the  muscles  they  penetrate  the  primitive  fibres, 
bring  the  adjacent  contents  of  the  fibre  to  degen- 
eration, and  grow  in  about  fourteen  days  to  fully 
developed  muscle  trichinae.  Iu  the  neighborhood 
of  the  trichinae  there  occurs  a  proliferation  of 
the  muscle-nuclei  and  an  inflammation  of  the 
connective  tissue.  .Vt  first  the  muscle -trichinae 
are  enclose<l  only  by  the  sarcolemma,  which  ap- 
pears thickened  and  liyaline  about  them.  Latei" 
there  occurs  in  the  neighborhood  an  inflammatory 

proliferation  of  granulation  tissue  containing  nu-  ^,     .Z    ^       „       ,„„ 

1  .,          n     /r-c   ,  ■•    .    ^         ,.,,*',  riG.  !)8->.— Sexually  mature 

merous  eosmophile  cells  (Schleip),  which  leads  to  trichina?,    .i,  Female;    B, 

the  production  of  connective  tissue   on  the  out-  Tm.   ^^^^""^  Leuckart.) 


rHiciiix  A. 


71.-) 


Ilh'  sai-culriiiiiia  hilir. 
ippcar  later  in  tin-  roii 
lallrlli("iiii,'rsp.Ti:ilI\ 


liuiitr.l  lifc.r  r 


nil 


t(.ri-li(    \\,-.lvs. 


;i\   li 


•V   Inn 


•U.      |H. 


FIG, 


side  of  the  sareoleimiia  and  iieneliales  even  w  itjiii 
themnsc'le-miclei  Innw^  desiioyed.      l-'al -cells  nia\ 
iioetivo  tissue  of  llieeapsnle,  the  de\  clopnieiil  of  tin 
marked  at  the  poles. 

The  intestinal  trichina-  liaxe 
The  luuscle-tricliina',  on  Ihe  (tih 
blyan  unlimited  time — 
that  is,  until  the  death 
of  the  atiected  individ-      ^l£' 
ual ;  or  at  any  rate  for      "~~   ' 
years,  althoutjjh,  accord- 
ing- to  Ehrhardt,    a  fe^ 
may  die  before  the   en-     i;--^, 
capsulation.   After  some 
time   there    frequently 
occurs   a  deposition   of 
lime-salts  in  the  capsule, 
especially  at  the  poles, 
causino-   it    to    appeal- 
iilistenin.u-white    by    ic- 
Hected  light,  and  cloudy 
and  dark  by  transmitted 
light.     In  rare  cases  the 
trichinre  after  dying 
also  become  calcified. 

Trichime  have  been  ol)served,  besides  in  man,  also  in  ilie  hog,  cat, 
dog,  rat,  mouse,  marmot,  polecat,  fox,  marten,  badger,  hedgehog,  an<l 
raccoon.  Through  the  feeding  of  trichinons  meat  muscJe-trichina'  may 
also  be  develoiied  in  rabbits,  guinea-i)igs,  shee)),  dogs,  etc.  ^Fan  becomes 
infected  through  the  eating  of  uncooked  pork.  The  invasion  of  tin'  tii- 
cliiuie  produces  various  phenomena  in  man.  The  introduction  of  tricliin- 
ous  meat  into  the  intestine  is  followed  by  the  symptoms  of  an  intestinal 
catarrh.  With  the  invasion  of  the  muscles  thei'e  are  prodnct'd  pain, 
swelling,  cedema,  paralysis,  and  not  infre<|uently  fe\<'r.  In  the  bloud 
there  occurs  a  marked  increase  of  the  eosinophil;'  cells  (Opie,  S<hleipi. 
The  symptoms  are  most  se\ere  in  thefoui-th  and  tilth  weeks.  I)e;ith  not 
iufrequently  results.  The  intensity  and  sexciity  of  the  symptoms  depend 
in  general  upon  the  number  of  the  woi'ms  Mandeiing  into  the  )nii>.cles. 

The  trichime  are  found  most  abundantly  in  the  diaphragm,  tongue,  in- 
tercostal muscles,  the  muscles  of  the  neck  and  larynx,  tlu^  bnnbaiinnscles, 
and  are  scattered  most  si)ai'Sely  in  the  distant  muscles  of  theextiemities. 
They  are  usually  most  numerous  about  tlie  insertions  of  the:  ten«lons. 

According  to  Frothinghnm  {Jour,  of  Med.  Res.,  ]<){)(]).  the  fricliiiui  cnihryic*  nro 
found  in  the  sinuses  of  the  mesenteric  lynii)li-iio(les  and  in  the  liver  siiuisoids,  ^liowinj; 
that  they  enter  the  lyiiiph-stream  and  are  distrilMite<l  l)y  the  ciiculaliiiK  I)1o(mI.  'rrichieia 
embryos  are  found  in  the  areas  of  ha-niorrluiKe  occurring  in  I  lie  liiii;;s.  hueal  destruc- 
tion of  tissue  may  take  place  in  the  liver,  i)ancreas,  brain,  and  heart  as  ji  result  of  the 
parasite  leaving  the  blood-vessel.  The  capsule  of  tlie  encysted  tricliina- is  fitrmcl  of 
connective  tissue  which  surrounds  the  whole  of  the  invaded  fibre. 


siiliiliHlm\iscl('tricliiii;i-.  (  Afti  r  Li-Uckii 


Literature. 

(Jfricliiiiti  Sjtirdlis  :   7' 


Askanazy:  Zur  Lehre  von  dcr  Trichii 

141  Bd.,  1895. 
Cerfontaine:  Contr.  a  let.  dc  la  trichiiH 

xxi.,  1S97. 
Cb.atin:   La  trichine  et  la  triehinose,  Paris,  ISS.'i. 


hinnsis.  ) 
("111.    I.    H.ikl.,  XV.,   IVU;    \irrh.  .\rrh. 


\i(h.dc  l.iol.,  xiii.,  IS'.KJ;    Cbl.  f.   Kakt., 


74ti 


THE    AMAIAL    PARASITF:s. 


Realencyklop., 
(Eosinophilic). 
irhi  trichinosc. 
.  S.  Bureiui  of 


Ehrhardt;  Muskelveriinderungen  hei  Trichiiiose.     Beitr.  v.  Ziegler,  xx.,  1896. 
Graham:  Xaturgesch.  d.  Trichina  spir.     Arch.  f.  mikr.  Anat.,  1.,  1897. 
Hert'wig':  EntwickeUuig  d.  Trichinenkapsel.     Miinch.  med.  Woch.,  1896. 
Johne;  Der  Trichinenschauer,  BerUn,  1904. 
Lang-erhans :  Ueber    regressive    Verand.   d.     Trichinen    u. 

Hirer  Kapsehi.     Virch.  Arch.,  130  Bd.,  1892. 
iiewin:  Zur  Diagnostik  u.  path.  Anat.  d.  Trichinose.     Dent. 

Arch.  f.  klin.  Med.,  49  Bd.,  1892. 
Opie:  Rehition  of   Cells    with    Eosinophile    Granulation    to 

Infection  with  Trich.  spir.    Am.  J.  of  the  Med.  Sc,  1904. 
Ossipow:  Yenind.  im  Spjitstadium  d.  ^luskeltrichinose.     B. 

V.  Z.,  xxxiv.,  1903. 
Riess:    Trichinenkrankheit.       Eulenburg's 

xxiv.,  1900. 
Schleip:    Homberger    Trichinosisepidemie 

D.  A.  f.  klin.  Med..  80  Bd.,  1904. 
Soudakewitsch:  Modi  fie.  des  fibres  muscul.  ] 

Ami.  (le  rinst.  Pasteur,  vi.,  1892. 
Stiles:  Trichinosis  in  Germany.     Bull.  30,  I 

Animal  Indus.,  1901. 
Volkmann:  Trichinose.     Beitr.  v.  Ziegler,  xii..  1894. 
Williams:  The    Frequency    of    Trichinosis    in    the    I'nited 

States.     Jour,  of  Med.>ves.,  1901. 
Zenker:  Virch.  Arch.,  18  Bd.;    Deut.  Arch.  f.  klin.  Med.,  viii. 

§  202.  Filaria  or  Dracunculus  medinensis,  the 
(Tiiiiiea-wonn  (Fig.  587),  is  a  thin,  thicad-iike 
female  worm  from  60  to  100  cm.  iu  length.  The 
males  (observed  bj^  Charles)  which  were  attached 
to  female  filarite,  were  only  4  cm.  long.  The  an- 
terior extremity  is  rounded  off,  while  the  j)Osterior 
tapers  into  a  ]>ointed  tail  which  is  curved  toward 
the  belly.  The  external  cover- 
ing consists  of  a  firm  cuticle, 
which  at  the  cephalic  end  is 
thickened  in  the  form  of  a 
shield.  The  intestinal  canal  is 
narrow  and  has  no  anus.  The 
uterus,  filled  with  young,  takes 
up  nearly  the  whole  of  the  body- 
cavity.  The  embryos,  which  are 
set  free  by  the  bm*sting  of  the 
mother- worm,  have  a  firm  cuticle 
and  an  awl-shaped  tail.  As  in- 
termediate host,  the  embryos 
seek  out  small  crustacete,  iu 
which  they  are  probably  taken 
into  the  stomach  of  man  with 
the  drinking-water.  In  Africa 
and  Asia  the  worm  is  of  fre- 
quent occuri-ence.  It  develops 
iu  the  skin  to  sexual  maturity 
and  causes  abscesses  of  the  af- 
fected regiou.  It  is  usually 
found  on  the  lower  extremities, 
especially  iu  the  region  of  the 
heels. 

Filaria  sanguinis  hominis  is 

Ki<;.  'i^:.  — Filaria  sive  Dracunculm  medinensii<.       the  name  givCU  to  the  7rtrrfC  (Fig. 
(After  Leuckart.)    Natural  size.  ^^^.  ^^  ^  ^.^^.^^^^  ^^.j^j^j^  ^^^^j.   j^^ 

Fin.  .588.— Embryo  of    Filaria   Bancrnfti,  known       +u^    i^i^^^i     „,,,i    i,.,^,,^i,    ^^f    ,„„,i 
SIS  FilniinmmiHinis  hominis.    (After  Lewis.)     X  400.        the     blOOd     aud    h  mph    Ot     mau, 


I'll.AUIA.  717 

and  a ro  about  CI.")  mm.  in  l«'n<;lli.  The  sexually  mature  wunn  is  lili- 
lorm,  the  male  alxmt  S  em.  loiii;  and  the  teniMle  J.">  em.  It  is  eaih-d 
Filaria  Bancroft!  alter  its  discdverer.  The  worm  inhai»ils  Hie  lymph 
vessels,  paitieulaily  those  of  the  serolum  and  lower  exl remit ies,  and  ma> 
be  i)resent  in  large  munber.s.  It  causes  lympiistasis  and  inlhimmal  ioii> 
which  lead  to  strcUinr/,s  of  the  bimph-nhmlswxnl  to  clrplnnilKiais-lihr  f/iirhii 
ing  of  the  tissue,  associated  Mith  ledema  and  lymplian.uiectasis.  Puruh-nt 
inllammations,  lymph-abscesses,  buboes,  chylous  li\(iro(ele.  mikI  ehylons 
ascites  may  appeal"  in  conse(iuence  of  its  picsence. 

Fioni  the  lymphatics  of  the  limbs  and  scrotum  the  eggs  :ind  end»ryos 
(O..-).')  mm.  long)  (Fig.  .■")SS)  ])ass  into  paits  of  tlu-  lymi)iiatic  system  :"ind 
into  the  l)lood.  giving  rise  to  luematuria,  ciiyluria,  :ind  chylous  diarrlnea. 
According  to  ^lanson  and  Scheube  the  lilaria'  ;ire  i»reseiit  in  the  blood 
taken  from  the  skin  only  during  the  night;  von  Linstow  explains  this 
phenomenon  as  due  to  the  fact  that  during  sleeji  the  i>eripheral  ves,sels 
become  dilated,  and  so  i)ermit  the  entrance  of  tiu'  (ilaria-,  while  the  cap- 
illaries, being-  narrower  during  the  day,  do  not  permit  such  entrance. 
The  ha^matnria  is  the  result  of  the  collection  of  embryos  in  the  blood- 
\  essels  of  the  urinary  tract.  The  chylnria  and  the  chylous  <liairh(ea,  on 
the  othei-  hand,  ai'c  due  to  the  oltst  ruction  b\-  the  ])arasites  of  the  tlunacic 
duct,  thus  causing  a  lymph-stasis  which  extends  to  tiie  l.Mnphatics  of  the 
bladder  and  intestine  and  there  occasions  the  esca])e  of  lymph.  Accortl- 
ing  to  Scheube  the  rupture  of  the  lymphatics  is  also  attended  by  a  ruj)!- 
ure  of  blood-vessels,  so  tliat  blood  beconu^s  mixed  with  the  lymph.  The 
embryos  may  pass  out  from  the  urinaiy  apparatus  through  the  urine. 

The  distribution  of  the  embryos  is,  according  to  ^Fanson,  acc<tmi)lished 
by  meansof  nn>S(piitos,  m  liich  take  U])  the  ])arasite  dui-ing  the  act  of  blood- 
sucking. In  the  mosqnitos  they  ])ass  tlirough  a  second  stage  of  de\clop- 
ment  and  are  then  (James)  aftei-  two  oi-  thiee  weeks  ready  for  the  infec- 
tion of  a  new  host.  Mauson  formeily  held  the  oi)inion  that  they  eidered 
the  water,  and  in  a  free  comlition  were  taken  up  in  the  water  into  the 
intestinal  tiact.  The  investigations  of  Janu\s,  Low,  (Jrassi,  and  Xoe,  Avho 
followed  their  development  and  migration  in  the  body  of  mos(pii(os, 
nuike  it  seem  probable  that  they  are  transmitted  lo  a  new  host  through 
the  bite  of  the  mosciuito. 

'J'lie  Filai'ia  s;inguinis  occurs,  so  far  as  is  known,  onl\  in  the  tropics 
(Brazil,  Egy])t,  Algiei-s,  :\rad:ig:iscar.  Zanzibar.  Soudan,  Sontli  Ciiina. 
Calcutta,  J>ahia,  ( Jnadi'ioiiix'). 

Of  the  Acanthocephala,  nematode-like  Avorms  ha\  ing  no  intestine, 
and  possessing  at  the  aideiior  end  a  retractile  proboscis  set  with  hooklets. 
the  most  important  is  the  IJeJiiiior/ii/)te>i.s  f/iffos.  The  male  is  1(>-1.">  cm. 
long,  and  the  female  80-50.  It  occurs  chiefly  in  the  intestine  of  tln'  i)ig. 
and  i)enetrates  into  the  intestinal  wall.  According  to  Lindemaiui,  it 
occurs  in  Southern  Eussia  also  in  man.  Tlui  rose  chafer  and  the  ]\biy 
beetle  serve  as  intermediate  hosts. 

The  Filaria  hancrofti  is  found  in  the  West  Indies  and  occ;isionaily  in  the  .Soutiiern 
States.     More  rarely  cases  are  found  fartlicr  north. 

Mackenzie  estimated  the  nuinl)er  of  filaria-embryos  present  in  the  total  .)ulk  of  tlic 
l)Iood  of  a  case  of  hajmatochyluria  closely  .studied  l)y  him  at  from  (liirty^six  to  forty 
uiillions.     The  patient  died  from  empyema;    during  the  disease  the  filarue  died. 

In  the  domestic  animals  numerous  filann-nprcirs  occurand  iidial)it  .htTereiit  ])ar(.s 
of  the  body.  Filaria  papHlam  is  a  common  parasite  of  the  liorse.  donkey,  and  caltle; 
it  lives  in  the  serous  cavities  and  reaches  a  lenjith  of  from  .'.-IS  cm.  Fthna  hawalica, 
.1  worm  13-1.3  cm.  long,  inhabits  the  right  heart  and  the  pulmonary  artery  of  the  doi:. 
arul  in  this  situation  gives  off  its  embryos  to  the  blood-stream.     It  occurs  |.articularly 


"48  THE    ANIMAL    PARASITES. 

ill  America,  China,  and  India.     Filaria  hcEinorrhagica  or  mult i papilloma  causes  a  nodular 
cutaneous  affection  in  tiie  liorse  and  donkey. 

Literature. 

{FUdfid. ) 

Barth.:  De  la  filaire  du  sang  et  ses  rapports  avec  I'elephantiasis  des  Arabes  et  ciuelques 

autres  maladies  des  pays  chauds.     Ann.  de  derm,  et  syph.,  1881. 
Blanchard:  Filaria  loa.     Arch,  de  parasitol.,  ii.,  1899. 
Charles:  History  of  the  Male  of  Filaria  ]Medinensis.     Scient.  Mem.  ^led.  Office  Army 

of  India,  vii.,  Calcutta,  1892. 
Firket:   De  la  filarose  du  sang.     Accad.  R.  de  mod.  de  Belg.,  Bruxelles,  1895. 
Goetze:  Die  Chylurie,  Jena,  1887. 
Grassi:  Filaria  inermis,  ein  Parasit  des  Menschen,  des  Pferdes  u.  des  Esels.     Cbl.  f. 

Bakt.,  i.,  1887;    Entwickelungscyclus  von  5  Parasiten  des  Hundes  (Taenia  cucu- 

merina,  Ascaris  marginata,  Sjjiroptera  sanguinolenta,  Filaria  immitis  Leidy  und 

H£ematozoon  Lewis).     Ibid.,  iv.,  1888;    Ha:>matozoon  Lewis  (Filaria  des  Hundes). 

lb.,  vii.,  1890. 
Grassi  u.  Hoe;  Uebertrag.  d.  Blutfilaria  durch  Stechmiicken.     Cbl.  f.  Bakt.,  xxviii., 

19()f). 
Havelburg-:  LTeber  Filaria  Sanguinis  und  Chylurie.     ^'irch.  Arcli.,  89  Bd.,  1882. 
Huber;  Bibliographie  d.  klin.  Helminthologie,  Suppl.,  Jena,  1898. 
James:  On  the  Metamorphosis  of  Filaria  sanguinis  in  ]\Ios(]uitoes.     Brit.  Med.  Jovu-n., 

ii.,  1900. 
Kasewurm  u.  Steinbriick:  Xematoden  bei  Haustieren.     Ergebn.  d.  a.  P.,  viii.,  1904 

(Lit.). 
Laveran  et  Blanchard:  Les  vers  du  sang,  Paris,  1895. 

Lewis:  (ieschlechtsreife  Form  der  Filaria  sanguinis.     Cbl.  f.  d.  med.  Wiss.,  1877. 
V.  Linstow:  Ueber  Filaria  Bancrofti  Cobbold.     Cbl.  f.  Bakt.,  xii.,   1892. 
liOthrop  and  Pratt:  Two  Cases  of  Filariasis.     Amer.  Journ.  of  Med.  Sc,   cxx.,  1900 

(Lit.). 
liOw:  Filaria  nocturna  in  culex.     Brit.  Med.  Journ.,  i.,  1900. 
Mackenzie,  St.:  Transactions  of  the  Pathological  Society  of  London,  1892. 
Manson:  The  Filaria  Sanguinis,  London,  1883;    The  Filaria  Sanguinis  Hominis  Major 

and  Minor,  Two  New  Species  of  Hsematozoa.     Lancet,   1891;    ref.,  Cbl.   f.  allg. 

Path.,  ii.,  1891. 
Mnrata:  Zur  Kenntniss  der  Chylurie.     ^littheil.  d.  med.  Fac.  dcr  Universitiit,  Tokio, 

1888. 
Peiper:  Tierische  Parasiten.     Ergebn.  d.  a.  P.,  vii.,  1902. 
Rieck:  Filaria  immitis  u.  ihre  Embrvonen  im  Blute  v.  Hunden.     Deut.  Zeitschr.  f. 

Thiermed.,  xiv.,  1889. 
Scheube:  Die  Krankheiten  der  warmen  Lander,  Jena,  1903. 
Sonsino:  The  Life-historv  of  Filaria  Bancrofti.     Brit.  Med.  Journ.,  i.,  1900. 


in.  Arthropoda. 

1.   Arachnida. 

§  203.  The  parasites  included  among  tlie  Arachnida  are  chiefly  epizoa, 
which  either  temporarily  or  permanently  inhabit  the  skin.  Only  one 
.species — Pentastoma—occnvH  in  the  larval  form  within  the  tissues.  Tlie 
most  common  parasites  of  this  group  belong  to  the  3Iites  (Jcarina). 
The  pentastoma  belongs  to  the  family  of  tongne-wormn  {Pentastomlihv  or 
Linf/inUi(Ji(l<r). 

(1)  Acarus  scabiei  f)r  Sarcoptes  hominis,  the  itch=mite,  is  a  para- 
.sitic  mite  tlie  size  of  a  pinliead  with  a  tnrtl('-shai)ed  body,  provided  on 
the  ventral  surface  botli  anteiioi-ly  and  ]>os1e]i()rly  with  two  pairs  of  legs, 
each  of  which  is  furnished  m  ith  bristles  (^Fig.  5S9).  The  anterior  pairs 
of  legs  extend  out  into  pedicled  clinging-discs.  The  same  arrangement 
is  found  in  the  posterior  two  pairs  in  the  male, while  in  the  female  both 
of  the  posterior  ])airs  end  in  long  1>ristles.     Several  bristles  are  also  found 


I'AHASI'IK       Ainilh'Ol'ol.  \, 


74<) 


along  the  border  of  the  i>()sterior  ijortion  «.r  tin-  body,  while  the  l)aek  is 
studded  witli  tooth-like  knobs.  The  head  is  round  and  Mkewise  s«'t  witli 
brii^tles.      Tlie  female  is  nearly  donble  the  size  o{'  the  iiuile. 


Fig.  589.— Female  itch-initc,  vcnlr;il  .siirfai't'.      X  lU. 

The  mite  lives  in  the  epidermis  (Fig.  o!M),  a,  d)  in  wliicii   ii    forms 
burrows,  some  of  which  are  10  cm.  long. 

In  the  burrows  the  female  ((/}  lays  the  eggs,  which  develop  //*  -situ 
into  the  young  itch-mites  (e),  which  penetrate  still  deeper  into  the  epi 
dermis,  and  after  repeated  sheddings  of  their  skins  grow  into  sexiiall.\ 
mature  animals.     The  skin  responds  to  the  irritation  producetl  by  the 


a.  - 
d 


•V"  -d  ^^-^ 


6    \ 


M  1;  J 


|ni 


<& 


<r^y 


Fig.  5iH).— ScabK  s  (.iloohol.  carmine)  a,  iiomv  lavfr  of  the  i  pldcrmlM  im  rfi.niU-fl  hy  iwuwnmt.  bur 
rows  of  the  iuli-mitt  ,  h,  iniKoiis  la>er,  and  paplllarv  1hm1\  the  latu  r  »rr.iiil\  »iilnivf<l  unc!  lnnUniU-< 
^vith  cells;  <•.  full's  intUtrdtid  with  (ells,  d,  s(<iii.ii  tlir.uu'h  i  full\  (l«  s.  li  i"  <l  If  h  itiltr ;  <.  .-(rirs  mi- 
embryos  of  different  sizes ;  /,  fieces.     X  'M. 


750 


THE    ANIMAL,    PARASITES. 


presence  of  the  mites  by  an  increased,  production  of  epithelial  cells  («  i 
and  inflammation  (e).  The  latter  is  still  further  increased  through  the 
scratching  of  the  spots  which  itch  in  consequence  of  the  invasion. 

2.  Leptus  autumnalis,  the  harvest-mite  (Fig.  591)  is  the  red-colored 
larva  of  a  variety  of  TromhidUUe,  wMch  lives  upon  grasses  and  bushes 
and  upon  grain,  and  when  occasion  offers  alights  upon  the  skin  of  man, 
where  it  penetrates  the  epithelium  and  causes  itching  and  inflammation. 

3.  Demodex  or  Acarus  folliculorum  hominis  (Fig.  592)  occurs  either 
singly  or  in  numbers  in  the  hair-follicles  of  the  face,  as  well  as  in  the 
ducts  of  the  sebaceous  and  Meibomian  glands.  Hausche  found  the  de- 
modex on  the  eyelashes  in  seventy-nine  per  cent.,  and  Joers  in  sixty-four 
per  cent,  of  the  cases  examined.  Children  under  one  year  of  age  were 
free.  The  female  is  0.4  mm.  long,  the  male  0.3  mm.  The  eggs  are  de- 
posited upon  the  shaft  of  the  hair  or  upon  any  other  portion  of  tissue,  and 
develop  after  two  sheddings  into  sexually  mature  animals  which  are  found 
in  the  entrances  to  the  hair-follicles  and  sebaceous  glands,  with  their  heads 
directed  inward.  The  assumption  that  the  demodex  causes  inflammation 
(acne,  blepharitis  acarica)  is  not  supported  (Joers,  Hausche),  since  in 
spite  of  its  presence  in  the  great  majority  of  cases  signs  of  inflammation 
are  wanting. 

It  has  on  its  anterior  ventral  surface  (Fig.  592)  four  i):iirs  of  short 
thick  feet.     The  lu-ad  possesses  a  snout  and  two  feelers. 

4.  Ixodes  ricinus,  the  icood-jacl'  or  icood-tiek  (Fig.  593),  is  a  faii^y 
large  yellowish- brown  member  of  the  Arachnida  belonging  to  tlie  ticks. 


Fig.  mv. 


Fig.  592. 


FIG.  .594. 


Fig.  591.-I/Cp/Msaua<//um'i^■.     (After  Kucheumeistfr  and  Ziirn.) 

Fig.  m-Z.—Acarusfollicuhwumhiiminis.     (After  Perls.)     X  3no. 

Fig.  .59:?.— JiTodes  ricimix^  sucked  half  full  of  blood.    X  2. 

Fig.  594.— Cephalic  end  of  Pcntastoma  denticulatum.     (Aft<?r  Perls.)  X 


J 


PARASITIC    AIM'IIIJOPOI)  A.  7.-,l 

It  has  n  black  head  provided  with  a  sucking  ajjparatiis,  and  a  very  dis 
tensible  leathery  body.  It  is  of  e(»imiM.ii  occiin-eiiee  u])()ii  <;rass  :iiiii 
bushes,  and  sometimes  alij^hts  upon  man  oi-  beast.  I'»y  means  nf  ii>, 
sucking  apparatus  it  diaws  blood  from  the  skin  and  swells  np  to  ;i  \,i  \ 
remarkable  extent. 

5.  Pentastoma  denticulatum  is  the  larva  of  Pentastoma  ta^noides. 
a  lancet-shaped  animal  belonging  to  the  tongue-worms  or  I'tnla.sloinida. 
It  inhabits  the  nasal,  frontal,  and  maxillary  ca\  ities  of  \aiions  animals, 
especially  of  the  dog,  very  rarely  of  man  (Laudon)  and  occasions  inllam 
mations.  The  female  of  the  mature  animal  is  50-SO  mm.  long,  and  an 
teriorly  from  8-10  mm.  broad;  the  male  is  10-22  mm,  long,  and  anteriorly 
from  3-4  mm.  broad.  The  body  consists  of  eighty-seven  to  ninety  seg- 
ments, the  most  anterior  of  which  bear  lateral  segment -a])i>endages,  the 
pairs  of  limbs.  The  eggs,  which  ai-e  produce<l  in  very  great  nnndnM-s, 
areoval.  The  larva  is  4-5  nnn.  long,  l.nmm.  broad,  pinmp,  llallened,  :ind 
inhabits  chiefly  the  liver,  lung,  or  spleen,  oi-  nM)re  rarely  the  (»1  her  organs 
of  man  and  the  herbivora.  It  occuis  in  the  form  of  a  small  nodide  «'ncap 
sulated  in  connective  tissue.  The  body  consists  of  about  fifty  ring  shaped 
segments  which  are  provided  at  the  borders  with  spines  (Fig.  ."i!)!),  and 
the  cephalic  end  is  provided  with  foui-  hook-sha])ed  fe<'l.  Tlie  eggs  are 
taken  in  from  the  external  world  thiongh  the  intestinal  tract.  The  para- 
sites set  free  in  the  intestine  wandei'  by  means  of  a  boring  apparatus 
through  the  mesentery  into  the  mesenteric  lymi^h-glands,  oi-  jienetrate 
direetly  into  the  blood-vessels,  and  are  cariied  by  the  blood-stream 
to  the  liver  or  even  to  the  lungs,  where  after  shedding  they  de\elop 
into  the  encysted  larvae.  The  larvai  may  in  their  wanderings  gain  access 
to  the  nasal  cavity  of  their  host,  and  develop  into  mature  animals,  al- 
though the  further  development  usually  takes  i)lace  only  after  their  re- 
ception into  a  new  host. 

According  to  the  published  reports  uf  Tnuakii  a  small  red  niiitj  occurs  in  gmit 
numbers  in  different  parts  of  Japan  during  midsummer,  and  clinging  tirmly  to  the  .skin 
of  man  causes  the  so  called  Ked(UU-(1iHPiii<e,  wliich  is  cliamcterizcd  li.v  intlanuuation  of 
the  skin  and  lymph-glands,  with  high  fever,  and  often  ends  fatally.  It  is  prol)able  that 
these  symptoms  are  due  to  secondary  infections  (proteus  and  streptococci)  in  the  bites 
of  the  mite.  Argas  refle.vus,  a  tick,  causes  by  its  bite  not  only  local  inHammalion.  but 
also  nausea,  diarrhoea,  cardiac  ])alpitation,  asthma,  etc.,  through  a  poison  ilerived  from 
its  salivary  glands.     It  is  found  also  in  jjigeons. 

In  the  domestic  animals  living  mites  occur  very  frecpiently  as  para.sitcs  of  the 
skin,  and  represent  different  species  of  various  families  {Siirroptvlrs,  Jhrniiitont/tlcK, 
Denmitopliayes,  and  Acari/lcs). 

Sarcoptes  hominis,  the  hurrow-mite  or  itch-mite  of  man.  is  foimd  al.so  in  horses  and 
Neapolitan  sheep.  In  addition  still  other  different  species  of  .sarcoptes  may  In-  distin- 
guished as  parasites  of  the  domestic  animals — for  example,  Sarcoptes  s(juumi/i  nix  in  dogs, 
nogs,  shecj)  and  goats,  and  Sarcoptes  minor  in  cats  and  rabbits. 

Dermnlophofjiifi.  the  devonnng-mite  (Fig.  59.5).  with  a  broad  head,  occurs  in  difTeront 
animals,  and  difterent  species  may  be  accordingly  distinguished.  It  lives  upon  flic 
cells  of  the  epidermis  and  causes  a  des(|uamatit)n  of  the  skin. 

Dermdtocoptes.  the  sucldmj-mite  (Fig.  .litfii,  with  long  narrow  hrad,  lak(;s  I)Ii>(mI  and 
lymph  from  the  skin  and  causes  inflanunation.  DermatocaptcK  communis  occurs  in 
horses,  cattle,  and  slieej). 

Dermafocoptes  cumciili  is  a  parasite  of  the  rabbit's  ear,  and  cauws  tlic  ear-seal. 
which  usually  appears  on  the  iiuier  side  of  the  auricle. 

S)jmbiofes  equi  of  Gerluch  is  a  mite  which  occms  chiefly  upon  the  feet  of  the  heiivy 
English  and  Scotch  horses,  and  causes  a  moist  dermatitis,  often  incorrectly  calle«i 
malanders. 

Dermanyssus  ariian  is  a  l<.Il^^  v<-<\.  l,l....d-snckiMg  mil.-,  .iboui  I  nun.  long.  nn<l  is 
often  found  upon  birds.  i      i  • 

Dermatoryctes  nuita^is  causes  tlie  fooi-iich  of  chickrns  wiicr<-by  theskui  :icr|um-s* 
mortar-like  scabby  coverinj;. 


^52 


l^HE    AXIMAT.    PARASITES. 


Acarus  follicidorum  or  Demodex  foil iculor urn,  the  mite  of  the  hair-follicles,  occurs 
most  frequently  in  the  dog  or  cat,  more  rarely  in  the  hog,  cattle,  and  the  goat.  In  the 
ilog  it  causes  the  formation  of  scales,  falling  out  of  the  hair,  and  a  pustular  eruption. 

Demodex  pln/Uoides  causes  in  swine  nodular  inflammations  and  ulcers  particularly 
on  the  snout,  neck,  breast  and  flanks,  and  the  inner  surface  of  the  thighs.  The  purulent 
toci  contain  great  luunbers  of  the  mites.     The  mite  may  develop  also  on  cattle. 


Fig.  595.— Male  of  Dermatopliayiis 
Fk;.  .590.—  Male  of  Dcrmatocoptis 


:  seen  from  the  ventral  side.  (After  Piitz.)     X  .50. 
,  seen  from  the  ventral  side,     (.\ftpr  Piitz.)    X  50. 


Various  species  of  Lmdcs  of  the  tick  family  occur  on  tlogs,  cattle,  and  sheep;  Argas 
rcjicxus  occurs  on  pigeons;    and  other  forms  of  ticks  occur  on  the  domestic  animals. 

Leptus  autumnalis  occurs  also  on  dogs  and  chickens. 

Penfastomata  occur  also  in  cattle,  sheep,  and  goats,  and  in  certain  regions  are  very 
common  in  the  first-named. 

S.   Tnaecta. 


§  204.  The  parasites  belonging  to  the  class  of  Insecia  are  for  the  greater 
part  epizoa.  In  part  they  are  bnt  transient  inhabitants  of  the  skin, 
deriving  from  it  their  nourishment;  in  part  they  are  permanent  inhabi- 


tants and  utilize  the  skin  structures  for  the  deposit  of  their  e^ 


Of  tht 


numerous  species  belonging  to  this  class  the  following  may  be  mentioned : 

(1)  Pediculus  capitis,  the  liead-lome  (Fig.  597),  inhabits  the  hairy 
portions  of  the  head,  and  derives  its  nourishment  (i.e.,  blood)  from  the 
.skin,  by  means  of  its  I'tMHling  apparatus.  Its  eggs  (nits)  are  barrel-shaped 
and  wliite,  and  are  attached  to  the  hairs  by  means  of  a  chitiuous  shell. 
The  embryo  hatches  in  al)out  eight  days.  In  consequence  of  the  scratch- 
ing induced  by  the  itching  tliere  often  arise  inflammations  of  tlie  skin,  in 
particular  eczemas,  Miiich  are  often  relatively  severe. 

(2)  Pediculus  pubis  (P///////-;//.s  iiu/uhiaHs),  the  felt  or  croh-Jou.sr  (Fig. 
598),  inhabits  1  lie  liaiiy  ])arts  of  the  trunk  and  extremities.  Its  habits 
of  life  ai'e  the  same  as  tlio.se  of  JWIIciiJk.s  rapii'iK. 

(3)  Pediculus  vestimentorum,  the  clothing  or  hody-Iome  (Fig.  599), 
lives  in  the  wearing  ai>])arel,  and  lays  its  eggs  in  the  same.  It  gets 
ii[)<tn  man  to  ol)tain  its  nourisliment. 


PAUAsrnc   Airi  iiHoi'oi)  \, 


rr>:{ 


(4)  Cimex  lectularius,  the  IxHlbnj;-,  <lwellsiii  l.rds,  il.x.is,  «1un.-i>,  .h  . 
DiH-iiiji;  tlu'  nijiiil  it  ucts  upon  man  In  suck  1»1«mm1.  Ii  «;iiis(s  w  IkmK  in 
the  skin. 

(5)  Pulex  irritans,  \\w  roiniiion  flea,  als.)  diaws  hlood  rium  ilir  skin. 
At  the  point  whei-e  it  has  sucked  tlierc  is  ioinid  a  little  punctate  ha-nmr 


Fu;..-)97. 


Fl(i.  597.— Female  of  PcdifidK.scrtpifi.s,  seen  from  the  ventral  surface.  (Kikhenmeisteninil  Ziirn.)    <  13. 

Fio.  598.— Male  of  PcdiciiJus  pubis,  seen  from  the  ventral  surface.    { Kiicheniiielster  and  Ziirn.)    .'  |;i. 

Fig.  599.--Female  of  Priliriihis  r<Ktimn)tunnii,  seen  from  the  v.-ntml  surface.  (Kiicheniiielster  aixl 
Ziim.;         !t. 

rhaj-e.  Occasionally  it  causes  wheals  and  swellings.  It  lays  its  e^os  in 
the  tracks  of  floors,  in  sawdust,  etc. 

(())  Pulex  penetrans  {Sarropsi/Ila  penctran.s),  the  mud Jitti,  occms  in 
South  At'ricai  in  the  sand.  The  leinale  lays  her  ejifisin  the  skin,  tln'rcby 
eausiug  an  inten.se  intiainniatioii. 

(7)  flosquitos  jnovidetl  with  stin<;inj;-  and  suckin;;-  apparatus  (Cnfiri- 
die  and  Tlpidhke),  horse-flies  {Tabanida),  and  flies  (tSfoiiHuj/idii)  draw 
blood  frequently  from  the  skin  of  man.     A'arious  flies  ((Kstridu;  biting 


Fig.  60n. 


p'u..  till].  Fifi.  wni. 

Inlhiimid  cnnicidaris.     f.\fter  Braiin.)     .AIkhiI 


Kl«.    lUtl. 


Fig.  600.— Larva  of  AnUiamid  cnnicidaris.     f. After  Braiin.)     .AIkhiI        <>. 

Fig.  601.— Larva  of  Musca  vomUoria.     (After  Brauri.)     About  X  6. 

Fig.  602. — Larva  of  Lncilia  inacellaria.    (After  Kniun.)     Alumt  x  il. 

Fig.  603. — Larva  of  Dcrmntobia  cyaniventris.     (After  Blanchanl.»     Alioiit  X  6. 

4.S 


754 


THE    ANIMAL    PARASITES. 


bot-flies,  3Iusci(lcv  or  hlow-flies)  occasionally  lay  their  eggs  iu  tlie  skin,  in 
ulcers  or  wounds,  or  in  the  accessible  body-cavities,  in  consequence  of 
Avhich  the  maggots  developing  cause  local  destructio]i  of  tissue  and  in- 
flammation {))}  ijimis) .  Under  certain  conditions  their  larvie  (for  example, 
thsht  of  Anfhomid  r(niiri(Jaris,  Fig.  600)  may  get  into  the  intestinal  tract 
with  the  food  and  there  undergo  further  development  (<y*//m.s/.9  IntcstinaJis).  , 
This  is  especially  likely  to  occur  when  abnormal  conditions  which  inter- 
fere with  digestion  are  present  in 
the  stomach  and  intestine.  The 
rffffs  of  the  Muhc'hIw  (in  Europe 
(ts</fp^  T    x  '^■^'^  \\^\^A\\J  of  SarcophU a  wohl fa rii  awiV 

"""-Jt^^'Z^/tL^  P%m^         j[„sra     vomifona    [Fig.  "BOI],    in 

.Vmcrica  of  Voiiipsomii'ta  or  LncHio 
iii((c('II((ria  [Fig.  002],  and  Jliiitca 
unihi-opophaga),  when  laid  upon 
the  mucous  membranes  or  in 
wounds,  hatch  after  a  few  liours, 
and  cause  destruction  of  the  neigh- 
boring soft  parts  through  their 
efforts  to  obtain  nourishment. 
In  the  auditory  canal,  nose,  and 
anti-um  of  Highmore  the  bones 
may  belaid  bare  (mj/iasis  mucom). 
In  the  course  of  about  a  week 
Ihe  larva)  leave  the  ulcers  and  pass  into  tlie  pupa  stage  in  the  earth.  The 
Q^stridw  (iu  Europe,  Hypodenna  hovls  and  Jfi/podenna  diana ;  in  America, 
Deniwtohia  cyaniventn's[Fig.  603]  or  Cidrrehra noxiaJi.s)lny  theiv eggfui^on 
wounds  or  in  the  intact  skin.  The  larvfe,  hatching  very  soon,  penetrate  into 
the  cutis  by  means  of  their  hooklets,  and  after  several  sheddings  grow  in 
from  one  to  six  months  into  larger  larvfe  about  2  cm.  long.  They  cause, 
particularly  in  their  later  stages,  painful  swellings  of  tlie  neighboring 
tissue  {myiasis  cvstrosa). 


Fig.   604. 


(After  Braupi- 


Parasites  beloiiiiiii":;  to  the  Muscidce  and  (JEstri^ihv  play  a  more  important  role  iu  the 
case  of  the  domestic  animals  than  in  man;  and  the  larvae  of  the  species  of  Oistrus  in 
particular  occiu-  as  ]i;iiasites  in  animals.  For  example,  the  larvae  of  Gastrophihis  eqid 
(Fig.  604),  Gast.  jxruiuni  and  Gast.  hcemorrhoidalis  inhabit  the  stomach  and  adjacent 
portions  of  the  intestinal  tract  of  the  horse,  where  they  complete  their  development  up 
to  the  ]3iipa-stage,  when  they  leave  the  animal. 

(Estrus  ovis  lays  its  larvae  in  the  nasal  cavities  of  sheep,  whence  they  may  wan- 
der, imder  certain  conditions,  into  the  frontal,  nasal,  and  maxillarj^  cavities,  or  even 
into  the  cranial  cavity,  and  excite  inflammation. 

Hypodenna  or  G'Jstrus  bon's,  the  biting  fly,  or  bot-fly,  lays  its  eggs  ujion  the  skin  of 
cattle.  The  larva  bores  into  the  skin  and  enters  the  spinal  canal  of  cattle,  completing 
here  its  development  up  to  the  piipa-stage,  at  which  time  it  leaves  the  animal.  Accord- 
ing to  Schneidcmiild,  the  larva?  do  not  always  enter  through  the  skin,  but  are  more  often 
taken  in  with  tlic  food,  whereu))on  they  penetrate  through  the  wall  of  the  oesophagus 
toward  the  skin  and  spinal  canal.  The'latter  follows  from  tlie  fact  that  they  are  found 
in  the  wall  of  the  a\sophagus  fi-om  October  to  January,  and  mider  the  skin,  on  the  other 
hand,  from  January  to  A))ril.      In  the  skin  they  cause  the  so-called  '"  fly-boils." 

Sarcophila  imhifarti  [Sarcopliaga  magnifica)  lays  its  larvae  upoti  the  skin  of  horses, 
sheep,  cattle,  dogs,  and  geese.  Lucilia  nmctllaria  lays  its  eggs  between  the  hind  legs  of 
Iambs  suffering  with  diarrhoea.  The  larvae  seek  the  thick-wooled  portions  of  the  root 
of  the  tail  and  the  lumbar  region  and  bore  into  the  skin. 


i'.\K' Asn  i( 


Literature. 

(PHnt-silic  Aiiif/niiilii  11,1(1   Insrrld.^ 

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I )t'iinatozoaires,  Paris.  1900. 
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Hausche:  Demodex  folliculorum  im  Augcnlide.     Miincli.  nicd.  ANDcli.,  liMiO. 
Hoffmann:  Fliegeiilarven  im  monschl.  Mageii.     Munch,  mod.  Woch.,  ISSS. 
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Kraus:  Farbetechnik  z.  Xachweis  ties  Acarus  folliculorum.     A.  f.  Derm.,  58  Bil  ,  19((1. 
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Uosp.  Rep.,  1899. 
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poden.     Ergebn.  d.  allg.  Path.,  vii.,  Wiesbaden,  1902  (Lit.). 
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1 899. 
Salmon  and  Stiles:  Sheej)  Scab.  Washington,  1898. 

V.  Samson-Himmelstierna:  Vaw  Jlautmauhvurf.     Arch.  f.  Derm.,  41  lid.,  lSi(7. 
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1S8.X 
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(Animal  I'ani.sifr.s. ) 

Blanchard:  Parasites  animaux.     Traite  de  path.  publ.  par  lioucliard,  ii.,  Is9ri. 

Braun:  Die  thierischen  Parasiten  des  Menschen,  Wiu-zburg,  1903. 

Davaiue:  Traite  des  entozoaires,  Paris,  1877. 

Huber:  Bibliographie  der  klin.  Helminthologif,  MiinchcM,   1S9I-98;  liibliogmpliic  drr 

klin.  Entomologie,  i.-iv.,  Jena,  1898-19(K). 
Johne.   Der  Trichinenschauer,  Berlin,  1904. 

Ktichenmeister  u.  Zurn:  Die  Parasiten  des  Men.schens.  Lei|)zig,  1nn2. 
Leuckart:  Die  menschl.  Parasiten,  Leipzig,  186.3-76;    2te  Aufl.,  ]S79-]9()1. 
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Neumann:  Traite  des  maladies  parasitaires  des  animaux  domesti(iues,    pjiri.-,    IS-SS. 
Parona:  L'ElmintoIogia  Italiana,  Genova,  1894  (Lit.  bis  z.  J.  lS90j. 


756  THE    ANIMAL   PARASITES. 

Perroncito-  T  parassiti  dell'  uomo  e  degli  animali  utili,  Milano,  1882. 

Stiles:  Bull.  llyg.  Lab.,  U.S.  Pub.  Health  and  Mar.  Serv.  ,,,,0 

Ward:  Articles  on  Parasites,  Arachnida,  Nematoda,  etc.,  m  Ret.  Handb.  ot  Med.  fee, 

•^d  ed 
Ziirn:  Die  Krankheiten  d.  Hausgefliigels,  Weimar,  1882;   Die  Schmarotzer  auf  uud  in 

dem  Korper  unserer  Plaussaugethiere,  i.,  Weimar,  1883-89. 


GENERAL  INDEX, 


Abdomixal  cavity,  faulty  closure  of,  520 

Abortion,  506 

Abrachius,  525 

Abrin,  poisoning  by.  26 

Abscess,  340.  364,  580 

burrowing,  368 

chronic,  368 

cold,  630 

congestion,  368 
Abscess-membrane.  364 
Acanthocephala,  747 
Acardius  acephalus,  541 

amorphus,  541 

pseudoacormus,  541 
Acarina,  748 
Acarus  folliculorum  liominis,  750 

scabiei,  748 
Acervuloma,  437 
Acervulus  cerebri,  229 
Aceto-acetic  acid,  77,  79,  80 
Acetone,  77,  79,  80 
Achirus.  528 
Achorion  schonleini,  685 
Achromatopsia,  52 
Achyla  proUfera,  687 
Acids,  corrosive,  22 

acid-intoxication,  79 
Acme  of  a  fever,  92 
Acne,  580,  750 
Aconitine.  poisoning  by,  29 
Acrania,  513 
Acromegaly,  85,  270 
Actinomyces  or  ray-fungus,  550,  659 
Actinomycosis,  659 
Acuminate  condyloma,  367,  442 
Addiment,  119 
Addison's  disease,  87 

pigmentation  of  skin  in,  239 
Adenocarcinoma,  448,  468 

development  of,  462 
Adenocystoma,  448.  452 

papillary,  452,  453 
Adeno-cysts,  487 
Adenofibroma,  447 
Adenoma,  440 

alveolar,  440 

carcinomatosum.  468 

conversion  of,  into  a  carcinoma,  4(\2 

papillary,  446 

tubular,  446 

umbilical,  522 
Adenomata  and  carcinomata.  difficulty  uf 

distinguishing  between,  447 
Adenomyoma,  482 


Adenoniyiis.ircoma,  492 

Ailenosarcoma,  477 

Adipose  tissue,  atrophy  of,  1!»3 

development  of,  295,  296 

patiiology  of,  193 
Adipositas,  49,  194 
Adrenalin,  87 
^gagropihe,  233 
Equatorial  plate,  280 
Aerobes,  557 

Age,  predisposition  in  old.  47 
Agenesia.  ISO 

partial,  of  the  cranium,  513 
Agglutination.  120,  121 
Agghitination  of  colon  bacillus,  ,')!t<.i 

of  typhoid  bacillus,  109,  597 
Agglutinins.  109,  119,  120,  121 
Aggressins,  39 
Agnathia,  518 
Agrotis  segetum,  687 
Air,  entrance  of,  into  the  right  heart.  70 

embolism,  70 
Albinism,  257 

Albuminoid  bodies,  jiroteclivc.  105 
Alcohol,  poisoning  by,  28 
Alexins,  104 

protective,  105,  106,  I  I'.t 
Algor  mortis,  169 
Alkaloids,  toxic  cadaveric,  33,  38,  557 

vegetai)le,  19 
Alveolar  .sarcoma,  425 
Ami)oceptor,  119 
Amelus,  525 
Amides,  553 
Amido-acids,  553 
Amins,  553 

Amitotic  nuclear  division,  283 
Amme.  716 

Amnion,  pathological  conditions  of.  500 
Amniotic  adhesions  a  cau.se  of  malforma- 
tions of  the  eml)ryo,  50 
Amceba  coli  felis.  (i90 

coli  mitis,  689 

coli  vulgaris.  689 

dysenteria',  ()89 
Amphibolous  .stage  of  fever,  92 
Am])himixis,  59 
Amputation  neuroma.  301.  I  Hi 
Amyelia,  total  or  j)artial.  .')0S 
Amyloid  concretions.  220 

degeneration.  214 

local  infiltration  of,  220 
Anabiosis.  I.  9,  10 
Ana'inia,  127,  133 


roS 


GENERAL    INDEX. 


An^nija,  chronic.  127 

collateral.  134 

due  to  hookworm,  738 

due  to  tapeworm,  734 

general,  127 

locahzed,  12<),  133 
Anaerobes,  551 
Ana  pi  a  si  a,  466 
Ana])hylaxis.  122 
Anasarca.  151 

Anatomy,  general  pathological,  2 
Anchylostoma  duodenale,  43,  737 

americana.  737 
Androgjnes,  536 
Anencephalia,  514 
Anencephalus,  total.  514 
Aneurism,  cirsoid,  402 
Angioma.  398 

arteriale  plexiforme,  402 

arteriale  racemosum,  402 

cavernosum,  400 

fissural.  399 

hypertrophicum.  402 

lymphaticum,  404 

plexiforme  arteriale.  402 

simplex.  398 

venosum  (varicosum),  411 
Angiomyoma,  410 
.Angiosarcoma,  429 
Anguillula  intestinalis,  741 

stercoralis,  742 
Anhydra-niia.  127 
Aniline.  ])()is()ning  by.  26 
Animal  diseases  caused  by  cocci,  584 

parasites,  42.  689 
Anopheles,  44,  710,  712, 
Antagonism,  bacterial,  552 
Anthomia  canicularis,  754 
Anthrax-bacilli,  589 

attenuation  of.  592 
Anthrax,  protective  inoculations  against. 
592 

symptomatic.  666 
Antibacterial  substances,  103,  ](t9.  118 
Antibodies,  33.  104,  105 
Antimonv.  poisoning  bv,  23 
Antitoxins.  33.  104.  108\  109,  112,  118,  119 

of  diphtheria.  117 

production  of,  122 
Anus,  condyloma  latimi  of  the,  643 
Aplasia,  167 
Aprosopia,  517 
Apus,  525,  528 
Apyrexia,  92 
Arachnida,  46,  48,  743 
Area  cerebrovasculosa,  514 

medullovasculosa,  508 
Argas  reflexus,  751 
Argyria,  256 
Arrhinencephalus,  515 
Arsenicismus,  pigmentation  in,  246 
Ai-seniurettetl  hydrogen,  poisoning  by,  26 
ArterioUths,  146 
.Vrteriosclerosis,  222 
Arterj',  obhteration  of,  149 

terminal,  163 
Arthritis  urica,  231 


Arthropoda,  748 

parasitic,  43,  46 
Ascaris  lumbricoides,  735 

megalc  ephala,  736 

mystax,  736 

suilla,  736 

vituh,  736 
Ascites,  153 

chylous,  166 
Ascococci,  549,  563 
Asiatic  cholera,  671 
Aspergillus  fiavescens  or  flavus,  41,  682 

fumigatus,  41.  682 

nidulans,  682 

niger,  or  nigricans,  683 
Aspergillus-mycoses,  682 
Asphyxia,  5 

local,  172 
Astrocyte,  304,  414 
Atavism,  55,  499 
Atheroma,  442,  519 

Atmospheric    pressure,    effect    of    an    in 
crease  of,  14 

effects  of  sudden  lowering  of,  13 
Atresia  ani,  524 

ani  vesicahs.  525 

ani  urethrahs,  525 

ani  iiterina.  525 

ani  vaginalis,  .325 

oris.  518 

recti,  524 

urethrae,  524 
Atrophy,  184,  369 

active,  187 

brown,  185 

desenerative,  186 

dis^use,  7,  189 

excentric,  185 

impaired  nutrition,  ISS 

neuropathic,  189 

passive,  187 

pigment,  185 

pressure,  188 

senile,  188 

simple,  186 
Atropine,  poisoning  by,  28 
Attenuation  of  bacterial  \-irulence,  1 12 
Attraction-spheres,  281 
Auditory   apparatus,   pathological   tniili 

tions  of,  52 
Auditory  meatus,  cholesteatomata  in.  4  1. 

mould-fungi  in,  679 
Autochthonous  pigment,  233 

teratomata,  496 

thrombi,  145 
Auto-intoxications,  75,  77 

enterogenous,  76,  77 

histogenous.  76 
Autolysin';  119 
Autolysis,  177,  191,  202 
Autolytic  ferments,  177 
Autosite,  545 
Awl-tail,  736 
Axis-cylinder,  sprouting  of.  304 

Bacili,-a^ce.e.  586 
Bacilli,  549,  586 


(IKXKKAL     INDKX 


Bacilli,  acid-fast,  621 

caj.sulated,  606 

pathogenic.  588.  .589 

j)c>lyinorplious,  588.  589 

saprophytic.  587 
Bacillus  aciili  lactici,  588 

acmjiouos  capsvilatus,  (>05 

amylohacter.  588 

anthracis.  589 

botulinus,  587 

butter,  621,  629 

butyricus,  588 

caucasicus.  588 

cholene  suis,  668 

coli  communis,  598 

comma,  671 

cyanojrenes,  588 

diphtheria'.  608 

dysenterise.  601 

enteritidis,  600 

Huorescens  liquefacicns.  .588 

icteroides,  614 

indicus.  551 

influenzjp.  607 

lepr:p.  649 

mallei.  654 

mucosus  capsulatus,  606 

necrophorous,  669 

nccroseos,  669 

necrosis,  669 

a^dematis  maligiii,  604 

]>aratyphosus,  600 

pertussis.  608 

pestis.  612 

phlegmoues  emphysematosa',  604 

})hosphorescens.  551 

pueimiouia^  of  Friedliinder,  606 

pi-ndigiosus,  588 

I  no!  (US  vulgai-is.  587 

pyoc  yaneus,  589,  601 

smegma,  621 

subtilis,  588 

sui  pestifer,  668 

sui  septicus,  668 

fcetaui,  602 

typhi  abdomiiiahs,  594 
Bacillus  of  anthrax.  589 

of  blackleg,  666 

of  bradsot,  667 

of  bubonic  plague,  612 

of  chancroid,  614 

of  chicken-cholera,  669 

of  contagious  pleuropnevunonia,  ()7(t 

of  diphtheria  of  calves,  669 

of  diplitheria  of  chickens,  669 

of  diphtheria  (jf  pigeons,  669 

of  glanders  and  farcy,  6.')4 

of  luemorrhagic  .septiciemia.  6()S 

of  infiuonza,  607 

of  lepro.sy,  649 

of  malignant  oedenia,  604 

of  mouse  typhoid,  668 

of  oziena,  606 

of  paratyphoid,  597 

of  pseuclodiphtheria,  610 

of  pyelonephritis  of  cattle,  669 

of  reindeer  plagr.e.  670 


Hacilius  ..f  rhiiioc.sleroma.  »l."i7 

of  swiiie-ery.sipelas.  667 

of  swilie-plllgue.  (iCS 

of  s\viiie-.septic:i'iiiia,  (M'tX 

of  symptonialic  anthrax.  litiC, 

of  tetanus.  60_> 

of  tuix'rculosis,  til 5 

of  tynhoid  fever.  .')!(» 

of  yellow  fever,  (il4 

of  whooping-cough,  60S 
Bacteria,  32,  549 

acid-resisting.  '»21 

action  of,  5.59 

aerobic,  551 

anaerobic,  551 

association  of,  559 

attenuation  of,  .560 

avenues  of  entrance  nf,  ;M 

cultivation  of,  .561 

degeneration,  forms  of.  5.51 

distribution  of,  :54 

ectogenic,  34 

endogenic,  34 

enzymes,  33,  5.56 

ferments,  33,  5.56 

intoxication  due  to,  ,35 

local  etTcfts  of,  35,  .562 

metastasis  of.  3(i,  5.59 

movements  of",  .5.50 

multiplication,  5.50 

non-i)athogenic.  .3.'! 

oligomorplious,  549 

parasitic,  551 

pathogenic.  30.  31'..  31.  .5.5S 

phosphorescence  of,  55S 

polymorphous,  550,  5S.S 

products  of.  33,  .39,  5.56,  5.57 

protection  against,  100 

red  sulphur,  .5.53 

saprophytic,  551,  .564,  .5'.i.s 

spores  of,  551,  553 

structure  of,  550 

that  cause  supi)urati()n.   .111.  5; 

toxins  of.  35 

transmi.s.sion  to  hetus  of,  5,'>o 
Bucteriacea',  586 
Bacterisemia,  36,  37 
Bactericidal  antil)odies.  H'.',.  ni'i 

inimune-bo<lies,  109 

sera,  122 
liacteriotrypsms.  .55(i 
Hacteriolysins,  119 
P.acterium.  .5S6 

coli  comimme.  59S 

lac* is  aerogenes,  (U»7 

of  ha'morrhagic.M'pti(;eiiii:i.r.''is 

typhi,  591 

vulgare.  .5S7 
Halanti(hnm  coli.  715 

Miinutum.  715 
liarber's  it<-h.  6.S5 
Barbone  dei  bufali,  669 
Barlow's  or  .Moeller's  diseas.-.  16(1 
Basedo'.v's  di.sea.s<',  .S5 
Bedbug,  or  ciine-:  K-c(ularius,  7.53 
Bedsore,  179 
Beg'i-iatoa.  5.50 


760 


GENERAL    INDEX. 


Benign  tumors,  383 

Beri-beri,  19 

Bezoar  stones,  233.  237 

Rijreraiinal  tissue-implantation,  J96 

Bile-pigment,  251 

Bilbarzia  luematobia,  719 

Bilirubin,  251 

Biophores,  60 

Birds,  malaria  of,  711 

tuberculosis  of,  037 
Biting-mite,  751 
Black  death,  612 
Black  gangrene,  178 
Blackleg,  666 
Bladder,  urinary,  papillary  epithelioma  of, 

441 
Blastoma.  371 
Blastomycetes,  41,  677,  681 
Blastomycetic  dermatitis,  41,  682 
Blastomycosis,  41,  682 
Blebs,  hsemorrliagic,  159 
Blennorrha?a,  340 

of  the  eye,  582 
Blister,  329,  332 

Blood,  antibacterial  properties  of,  103 
coagulation  of,  135 
extravasations  of,  158,  243 
increase  in  mass,  127 
parasites  of,  693,  695,  707 
protective  pov>ers  of,  103,  109,  119 
Blood-cells,  red,  new  formation  of,  297 

■\\hite,  new  formation  of,  298 
Blood-coi-puscle  cells,  243 
Blood-corpuscles,  red  and  colorless,  298 
Blood-current,  slowing  of,  138,  139,  320 
Blood-hyalin,  225 
Blood-plates,  140,  141 

escape  of,  from  the  blood-vessels,  323 
thrombus  of,  140 
Blood-poisons,  25 
Blood-pressure,  124 

increased  arterial,  128 
increased  pulmonary,  129 
lowered  arterial,  128 
lowered  pulmonary,  129 
Blood-serum,  bactericidal  action,  103 

immunizing  power,  112 
Blood-vessels,  alterations  of  walls  of.  320. 
340 
hyaline  degeneration  of  the  walls  of, 

222 
new  fomiation  of,  288 
Body-louse,  752 
Bone,  in  dermoid  cysts,  491 
necrosis  of,  365 

pathological  new  formation  of,  3(57 
reproduction  of,  293 
Bone-marrow,  reproduction  of,  295,  299 
Bones,  supernumerary,  .534 
Bone-tissue,  new  formation  of,  293 
Bothriocephalus  cordatus.  734 
felis,  734 
latus,  43,  7.32 
latus  liguloides.  734 
latus  Mansoni.  734 
Botryococcus  ascoformans,  58.5 
Botryomyces,  .585 


Botryomyco.sis,  585 
Botrytis  bassiani,  087 
Botuli.'smus,  19,  587 
Brachygnathia,  518 
Brachyphalangism,  528 
Bradsot,  667 
Brain,  concussion  of,  10 

development  of,  510 

telangiectatic  tumor  of,  399 
Brain-hernias.  514 
Brain-sand,  228 

Brain-substance  in  dermoid  cy-^ts.  491 
Brancliial  cysts.  519 

fistulas,  518 
Breast,  see  also  Mammar;/  ghmd 

adenoma  of,  445,  446 
Breasts,  supernumerary,  534 

well-developed,  in  men,  534 
Bronchial  calculi,  234 
Bronchitis,  purulent,  339 
Bronchopneumonia,  339 
Brood-capsules,  727 
Buboes  in  plague,  612 
Bubonic  plague,  612 

protection  against.  115 
Budding-fungi,  40,  677 
Budding  of  cells,  288 
Burns.  8 
Butter-baciUi,  621 

Cachexia,  5,  168 

suprarenal,  87 

thyreoprival,  82 

tumor,  384  _ 
Cadaveric  alkaloids.  19 

petechise  or  lividity,  132,  109 
Cadaverin.  33,  557 
Calcaneus,  chondroma  of,  392 
Calcification,  147,  220 
Calcium,  role  in  coagulation,  138,  142 
Calculi,  biliary,  234 

bronchial,  234 

dental,  233 

intestinal,  233,  237 

prostatic,  234 

salivary,  233 

urinary,  235,  237 
Callus,  209,  302 
Calmette's  theory  of  anthraco^is,  637 

tul^ercuhn  reaction.  022 
Calvarium,  atrophy  of  the,  187 
Cancer,  see  also  under  Curcinoma,  455 

cells,  457 

cells,  hydropic,  192,  475 

cylindrical-celled,  472 

endothelial,  428 

etiolosrv  of,  450,  458 

flat-celled,  409 

horny,  470 

medullary,  472 

milk,  1.57 

plugs,  468 

umbilication,  458 
Cancroids,  466 
Cantharidin,  22 

Carbon-dioxide,  influence  of,  upon  devel- 
opment of  bacteria,  ,551 


(iKXKHAL     IM)K\. 


701 


Carbon-niouoxicle-fias  jioi^^oiiiui;.   },  _>,') 
Carbon-bisulphide  (xiisunini:,  'JH 
Carcinoma,  4r)r>,  KiS 

acinosum,  472 

adenomatosvim.  4()S,  472 

basal-celled,  471 

branchioofenic,  488 

calcification  in,  476 

chorionic,  474,  484 

colloidos,  474 

cyliiulncal-celled,  472 

cylindroma tosum,  475 

ilevelopment  of,  455,  460.  465 
in  adenoma,  462 
in  glands,  4(52 
in  mi)co\is  membranps,  1(51 
in  papillary  epithelioma.  AiY-i 
in  skin,  460 

different  forms  of,  467 

durinii,  473 

etiology  of,  456,  458 

formation  of  metastases  in,  4S0 

gelatinosum,  474 

giganto-cellulare,  475 

healing  of.  477 

hyaline  degeneration  in,  475,  47(3 

implantation  of.  484 

infiltration  of.  457,  480 

meduUare,  472 

metastasis  of,  457,  480 

mucosum,  474 

myxomatosvmi.  475 

papilliferum,  478 

parasites  a  possible  cause  of,  456,  458, 
705 

petrifying,  476 

physaliferum,  475 

placental,  465 

recurrence,  484 

retrograde  changes  in,  457 

scirrhosimi,  473 

simplex,  472 

solidum,  468 

squamous-celled,  469 

structure  of.  467 

subcutaneous,  488 

transplantation  of,  484 

tubular,  4/2 
Carcinomata,  455 

complete  petrification  of,  476 
Cardiac  nmscle,  new  development  of,  302 
Caro  luxurians,  369 
Cartilage,  hyaline,  reproduction  of,  293 

in  dermoid  cysts,  482 

metaplasia  of,  315 

pigmentation  of,  241 

transformation  of,  into  reticular  tis- 
sue, 315 
Caseation,  175,  345 

in  tubercles,  620 
Castration,  effects  of,  88 
Catarrh,  329 

chronic,  368 

desquamative,  332 

nnicous,  332 

purulent,  332,  340 

serous,  331 


("attic,  actinomycosis  of,  65!* 

tuberculosis  nf,  (537 
Cattle-pcst,  114.  ,585 
Cattle-plague,  115,  .-)S4 
Caustics  or  corrosive  agents,  _'_» 
Cavernous  tvunor.  100 
Cavitv-fomiatidu  in  tuhcnMilnsis.  iV.'.U 
(Vinxvplialia,  515 
('('ll-divisiou,  280 
(Vil-protoplasMi,  division  of.  2S2 
Cells,  hyaline  products  of.  225 
Central  corpuscles,  280 

group,  118 

nervous  system,  regeneration  of,  3(»3, 
306 
Centrosomes,  280 
Ceiihalocele,  514 
Cephalot  horacopagus.  512 
Cercariir,  716,  717 
Cercomonas  inlestinalis,  692 
Cerebrospinal  canal,  deficient,  closure  f)l. 
513 

meningitis,  epidemic,  577 
Cerebrum,  glioma  of,  413 

malformations  of,  514 
Cestoda,  721,  742 
Chain-cocci.  550,  563,  ,565 
Chancre,  hard,  642 

soft,  614 
Cheese-poisoning,  19 
Cheesy  degeneration,  175 
Cheilo-gnatho-palatoschisis.  5 1 7 
Chemicals,  as  producers   of   suppuration, 

342 
Chemotaxis,  348,  554 

and    chemotropisnuis,    neicative    and 
positive,  102,  348 
Chemotroi)isnuis,  3-18 
Chicken-cliolera,  669 

innmmization  against,  113 
Chilblains,  9 

Children,  prc(lisi)o.-ition  of,  47 
Chills,  91,  93 
Chionyphe  Carter!.  665 
Chloasma  uterinum,  238 
(Chloral  hydrate,  poisoning  by,  2S 
Chloroform,  jjoisoning  by,  28 
Chloroma,  435 
Chlorosis,  Egyptian,  73.S 
Cholaemia,  76 
Cholera,  Asiatic,  671 

protective  inoculations  aiiain-t.    Ill, 
67! 
Cholera-red,  (574 
Choleratoxopeptone.  674 
Ciiolesteatomala.   112.   ISO 
Cholesterin,  203 
Cholesterin-calculus,  234 
Cholin,  38,  557 
Chondroadenon)a,  492 
Chon.lroblasts.  29.'.  293 
Chondroitin-sulphurie  acid,  21() 
Chondroma,  391 
Chondromyxoma.  3S7,  39.3 
Chondromyxosarcoma,  .392 
Chondrosar;-oma,  3'I3,  4!»2 
Chordoma.  393 


762 


GENERAL    INDEX. 


Chorio-epithelionvj,  4()(i.  47  K  4'J4 
Chorionic  villi,  caicinnmatous  transforma- 
tion of,  465 
C'hromaffinic  colls,  SS 
Chromatin,  280 
Chromatophores,  239,  43o 
Chromosomes,  280 
Chylangioma,  405 
Chylopericardium,  lOG 
Chyluria,  166 

Cicatricial  tissue,  274,  347,  354 
Cicutoxin,  poisoning  by,  28 
Ciliates,  715 
Cimex  leetularius,  753 
Cinnabar,  in  a  tattooed  skin,  255 
Circulation,     collateral,    development    of, 
133,  134 
of  the  blood  and  of  the  lymph,  dis- 
turbances in,  124 
Cirrhosis  of  the  liver,  370 
Cirrus,  723 
Cirrus-sac  of  Bolhriocephalus  latus,  732 

of  taaiia  solium,  723 
Cirsoid  aneurism,  403 

neuroma,  418 
Cladothrix,  550 

asteroides,  665 
Clavus,  269 
Clay  eaters,  739 
Cleft-foot,  528 
Cleft-hand,  528 

Cleft  of  the  abdominal  wall,  521 
Clefts,  504 

of  the  face,  median,  518 
of  the  face,  oblique,  517 
of  the  thorax,  521 
CUmate,  influence  of,  upon  man,  32 
CUtoris,  malformations  of,  524,  537 
Cloaca,  formation  of,  524 
Clostridium,  549,  586 

butyricum,  588 
Clothing-louse,  752 
Clots,  post-mortem,  135 

lardaceous,  135 
C'loudy  swelling,  190 
Clubbed-hand,  530 
Club-foot,  congenital,  529 
Clustered  cocci,  549 
Coagula.  substitution  of,  361 
Coagulation,  135,  136,  141,  322 
Coagulation-necrosis,  1 74 
Coagulins,  119 
Cocaine,  poisoiiintr  l)y.  2S 
Cocci  or  cocca'cp,  5!'.',  .')()3 
pathogenic,  .'>()!    5(1.') 
saprophytic,  56 1 
Coccidia.  42,  701 

reproduction  of,  704 
Coccidioidal  granuloma,  41 
C/Occidium  fuscum,  705 
oviforme,  101 
schubergi,  704 
Coccus  mesenterioides,  564 
Coccygeal  region,  bigerminal  teratoma  of, 

546 
Ccenurus  cerebralis,  726 
Coitus  (Hsease,  697 


Colchicine,  poisoning  ))V.  29 
Cold,  effects  of,  9 

abscesses.  630 
Colds,  9 
Collateral     circulation,     development     of. 

133,  134 
Colles'  law.  62 
ColUdin,  38,  557 
Colli(|uation-necrosis,  1 7(5 
Colloid.  209 

cancer,  474 

different  uses  of  the  term,  2f ! 
production    of,    bv     epithelial    cells. 
210 
Color-bUndness,  52 

Colorless  blood-corpuscles,  emigration  of, 
321 
increase    of,    relativelv    to    the    red, 

321 
marginal  disposition  of,  32 1 
Coma  diabeticum,  79 
Commotio  cerebri,  16 
Compensatory  hypertrophy,  8,  127,  2(i8 

of  tlie  heart-muscle,  127,  268 
Complement,  119 
Compsomyia,  754 
Conceptional  infections,  61 
of  syphihs,  62.  648 
of  tuljerculosis,  636 
Concietions,  226 
amvloid.  220 
calcareous.  228,  237 
free,  in  the  bodv.  233 
uric  acid,  235,  237 
Concussions,  effects  of,  16 
Condyloma  acum.inatum,  367,  442 

latiuu,  643 
Congenital  predisposition,  46 
Congestion,  130 
Congestive-abseess,  368 
Conglutination,  140 
Conidia-heaicrs,  678,  6,80 
Conidia-si)orcs,  678 
Coniine,  poisoning  by,  29 
Connective    tissue,    hvalinc    degeneration 
of,  222  \ 

transformation  of,  into  bone.  315 
Connective-tissue  structures,  regeneration 

of,  29 1 .         .         . 
Constitutio  epidemica,  33 
lymphatica,  89 
pestilens,  33 
Constitutional  diseases,  49,  81 
Contagion,  definition  of,  30 
(bntagiuni  animatum,  32 
Continuous  fever,  92 
Corivalescence,  92 
Coprannia,  76 
Coinila.  710 
Cor  ^■illosuln.  333 
Cordyce})s  militaris,  687 
Corn,  213,  269 

Cornification  of  epithelium,  212,  443,  705 
Cornu  cutaneum,  264,  441 
Cornutin.  23 
Corjjora  amylacea,  220 
Corpulence,  49 


II 


CKXKK'AL     l\l)i:\. 


Corpus  luti'Min.  fuuciioii  of,  S'.i 
e'oiTosive  agents,  2J 
Coiyncbac'tcriiiiu.  till) 
C'otton-niill  aiui-inia.  7:;'.i 
CowpoN,  111.  70.".,  707 
i'ows,  tulH'iculous,  milk  troiu.  (iSS 
('i:il)-li)us(",  732 
I'raniopa'ius,  ,")4J 

frontalis.  .341' 

offipitalis,  ,542 

pa  riot  a  lis,  ,')42 
("raniorachiseliisis,  513 
( 'raniosc'l i isis,  o  1 '.) 
Craniiuii.  faulty  ilevelopnirnt  of,  .".i:) 

partial  agenesia  of,  .'•,]:] 
(  raytish  pest,  087 
I  icnotliiix,  ,550 
(  n'tinisni,  83 

operative,  83 
( 'risis,  in  fevens,  92 
I  "rossed  embolism,  65 
( 'roupoiis  exudate,  332 

membrane,  formation  of,  on  mucous 
surfaces,  333 

pneumonia,  335.  577 
Cruor,  135 

<  "ryptogenic  infectious.  41,  573,  580 
I  'ryptorchismus,  531 

( 'ulex  pipiens,  698,  712 

("ulicidte,  7.53 

Culture,  methods  of  bacterial,  56i 

Curariue.  poisoning  by.  29 

Cutaneous  horn,  264.  441 

('uterebra  noxialis.  754 

Cyanosis,  125,  132 

Cyclencephalia  or  cycloceplialia.  515 

Cyclopia,  515 

Cylindrical-celled  cancer,  172 

Cylindromata,  438 

Cystadenoma,  44S 

mulrilocular,  448 

pupillary,  448 
(  yst-fonnatfon.  2.58 
( 'ysticercus  bovis,  725 

cellulosa'.  724 

pisiformis,  726 

racemosus,  724 

tenuicollis,  726 
T'ystin,  77 
("ystin-caleuli,  237 
Cystocarcinomata,  478 

papilliferum,  478 
Cyst  of  echinococciis,  728 
( 'j^stofibroma,  453 

<  'ystomata,  448 

multilocular.  448 

paiHllary,  448 

simplex,  448 
Cystomyxoina,  4.53 
Cystosarcoma,  453,  492 
lysts,  branchial,  486,  579 

dt'iicncration,  260 

(If-rmoid,  4S5,  490 

ectodermal,  485 

entodermal,  486 

mesodermal,  486 

retention,  2.58 


(  y>is,  snnplc  icratoid.   I,S5 

traumatic  epitli(4i.il.   K'iti 
Cyst -worm.  727 
Cvta.se.   104,  I  19 
Cytolysins.  120 
Cytotoxiii.  120 

D.VLTOMS.M,  52 

Darier's  di.seas<',  705 

Darwin,  56 

Daughtcr-cvsis  ..f  .•.■IiImocmtiis,  72S 

Daughter-si ars.  2S1 

Daughter-tumcM-s,  3S() 

Deaf  mutism,  .52,  .5.) 

Di'atii,  1,  16S 

apparent,  1.  170 

spots.  1.32,  169 
l)(>composition,  169,  .557 
Decubital  necrosis,  !73 
Decubitus,  173,  178 
Deer-tli.sea.se,  670 
Defect,  269 

Defervescence,  period  <>;'.  in  lever.--.  92 
Degeneration,  amvloid.  214 

colloid.  209 

fatty,  193.  19S 

granular.  190 

glycogenic.  205 

hyaline,  209,  222 

hydropic.  192 

lardaceous.  214 

nuicoid.  207 

parenchymatous.  I'.iO 

waxy.  175 
Degenerations,  167,  ISO 
Deiter's  cells,  304 
Demodex,  7.50,  7,52 
Dermanyssus  avium.  75! 
Dermatobia  cyanivenlris.  75:;.  75  1 
Dermatocoptes,  751 

comnumis.  751 

cuniculi.  751 
Dermatocysts.  4S5 
Dermatomyco.sisdilTusa  flc\orum.  (isO,  6s7 

furfuracea.  686 
Dermatophagus,  751 
Dermatoryctcs  nuitans,  751 
Dermoid  cvsis,  486,  490 
Dermoi.ls,"4S(i,  491 
Desmobacteria,  519 
[>esmoid  tumor,  385 
Destructive  placental  polyps,  466 
Determinants  or  determining  pieces,  60 
Deuterotoxin,  610 
Development,  distnrl.ances  of.  I'.IS 
Dial)etes  meliitus.  79 
Diabrosis,  1.59 
Diape.le.sis,  160.  322,  321 
Diastatic  ferments,  5.56 
Diastematomyelia,  51  I 

Diatlxsis,  iia-tnorrhairic,  160 ' 

Dicephalus  and  diprosopus.  542 
Digestive  juices,  action  upon  to.xins,  98 
Digitalin  and  digitidein.  j.oisoning  by,  29 
Dimcthvliunin.  ::s 
Diphtheria.  COS 

!>acillus  of.  COS 


7(34 


GENERAL    INDEX. 


Diphtheria,    blood- serum    treatment    of, 
112,  114, 115 

columbarum,  669 

of  calves,  669 

of  chickens,  669 

of  pigeons,  669 

toxin,  610 
Diphtheritic  inflammations.  .344 
Diphtheritis,  344 
Diplococci,  .549,  563,  575 
Diplococcus  intracellularis    meningitidis, 
577.  585 

lanceolatus,  575 

pnemnoniaj   (F  r  a  e  n  k  c  1 ,   ^^'eichsel- 
baum),  575 

rheumaticus,  574 
Diprosopus,  542 
Dipygus,  543 

parasiticus.  547 
Disease,  extrinsic  causes  of,  4 

generalization  of,  63 

intrinsic  causes  of,  53 

invasion,  42 

latency  of,  1 

sequelse  of,  72 

spread  of,  63 

the  symptoms  of,  1 

trophoneurotic,  74 
Diseases,  cause,  origin,  and  course  of,  1 

congenital,  44,  53,  61 

constitutional,  49 

general,  75 

inheritable,  44,  48,  53,  58 

intrinsic,  48 

local,  2 
Displacement  of  tissue  as  a  cause  of  tumor- 
formation,  376,  485 
Dispora  caucascia,  588 
Distoma  felinetim,  719 

haematobium,  719 

hepaticum,  716 

lanceolatum,  717 

pulmonale,  718 

sibiricum,  719 

spathulatum,  718 

westermanni,  718 
Distomia,  518 
Disu.se  atrophy,  189 
Diverticulum,  Meckel's,  521 
Dochmius  duodenalis,  737 

.stenocephalus,  740 

trigonocephalus,  740 
Double  monsters,  539 

symmetrical,  541 

unequal,  541,  545 
Dourine,  697 

Dracuncuhis  medinensis,  746 
Drill-bone,  397 
Dropsy,  151 
Druse,  660 
Ductus  thoracicus,  obstruction  of,  166 

occlu.sion,  154 

raptvu-e  of,  166 
Duett  is  omphalomesaraicus,  522 

thvreoglossus,  486 
Dung-fungi,  621 
Duplications,  532 


Duplicitas  anterior,  541 

parallela,  543 

posterior,  542 
Dura  mater,  endothelionia  of,  427 

osteoma  of,  396 

psammoma  of,  437 
Dust-diseases,  16,  367 
Dust-particles,  entrance  of,  into  the  liody, 
65,  256 

metastasis  of,  65 

protection  against,  98 
Dwarfs,  49,  181 

formation  of,  181 
Dyschromatop.sia,  52 
Dyscrasia,  168 
Dy.sentery,  bacillary,  601 

due  to  amoeb?e,  690 

of  calves,  669 
Dystopia  renis,  531 

Ear-scab,  751 
Eburneous  osteoma,  394 
Ecchondro.sis,  392 

physalifera  sphenooccipitalis,  393 
Ecchymoses,  158 
Echinococcus  alveolaris,  730 

granulo.sus,  729 

hydatidosus,  729 

multilocularis,  739 

scolecipariens.  729 

veterinorum,  729 
Echinococcus-cyst,  43,  728 
Echinorhyncus  gigas,  747 
Eclampsia,  77 
Ectodermal  cysts,  485 
Ectogenic  bacteria,  34 
Ectopia  cordis,  521 

cruralis,  531 

cruroscrotalis,  531 

inguinalis,  53 

interna,  531 

intestini,  521 

pubica,  531 

testis,  531 

vesicae  urinaria",  521 
Eczema,  580 

marginatum,  686 
Effusions,  chylous,  166 

inflammatory,  329 

purulent,  340 
Egyptian  chlorosis,  738 
Ehrlich's  .side-chain  theory.  118 
Elastic  fibres,  development  of,  292 
Electric    discharges,    powerful    effect   of, 

157 
Elephantiasis,  263,  269,  367,  531,  747 

Grsecorum,  64i) 

hsemangiomatosa,  263,  401 

iipomatosa,  263 

lyniphangiectatica,  263 

neuromatosa,  263,  417 
EmboHsm,  64,  65,  68,  149 

air,  70 

crossed,  65 

fat,  67 

paradoxical,  65 

retrograde,  65 


GKNKKAl.    l\I)i;\, 


Embolus,  ridiusr,  G8 

septic.  1-lS"' 

straddling,  GS 
l^^mbiyoid  tumors,  492 
Embryonia,  492 

Riubryonal  ti.^suo,  transplantation  of.  :'>1  I 
I'jubryonic  tissue,  291 

development  of,  in  a  thron;l)osed  ar- 
tery, ;^()2 
Emigration  of  white  cells.  .")21 
Emphysema  of  the  skin,  70 
Emphysematous  gangrene.  17S.  ()04 
Empu.sa,  varieties  of,  GST 
Empyema,  340,  3G4 
Encephalocele,  514 

Encpphalomeningocele  nasofronlali-.  .')14 
Enchondroma,  391 
Encranius,  ,547 
End-artery.  132,  1G3 
Endocarditis,  571 
Endochondritis  syphlUtica,  G4S 
Endothelial  cancer,  42S 
Endothelioma,  425 

hiemangiotic,  482 

lymphangiotic,  425 
Endothelium,  proliferation  of,  2SS 
Endotoxins,  33,  39,  557 
Engastrius,  547 
Enostoses,  394 
Enterocysts,  487 
Enterogenous  intoxication,  70 
Enteroliths.  233 

Entodermal  epithelial  cysts,  476 
Entodium  caudatum,  715 
Entogenic  parasites,  31 
Entozoa,  42 
Enzymes,  39,  9S,  556 
Eosinophile  cells,  225,  744,  745 
Ephelides,  406 
Epidemic,  definition  of,  31 
Epidermoids,  443,  485 
f^pigastrius,  547 
Epignathus,  547 
Epipygus,  546 
Epispadias,  .521,  524 
Epistaxis.  156 

Epithelial  cysts,  ectodermal,  entodermal, 
and  mesodermal,  478 

after  transplantation,  312 

dermoid,  478,  490 

epidernn)id,  478 

traumatic,  466 
EpitheUal  pearls,  213,  442,  470 
Epithehoid  cells,  301,  351,  609,  618 
JOpithelioma,  440 

adenoniatosum  benignutn,  440 

contagiosuni.  702 

l)apillary,  440.  442 

.syncytiomatodes.  495 
Epithehum,  atypical  growth  of,    in    carci- 
noma, 455 

hyperplasia  of,  286 

metaplasia  of,  318 

misplaced,  development  of  a  cancer 
from,  465 

pathological  cornification  of,  212,  4  1.5 

protective  powers  of,  97,  100 


Epithelium,  regeneration  and  hvii.  riihsiu 
of,  286 

transi)lantati(>n  of,  .'MO.  ISO 
l-pizoa,  42,  7.')2 
Ergcitism.  23 
l':rysip,-las,  .-)67 
i'.rvtiiema  nuiltiforme.  571 
I'.rytlu-asma.  41.  6S6 
l-'.rytiu-ohlasts,  297 
Ivrythrocytes,  regeneration  of,  297 
Erythrocyfolysis,  !3(> 
l!rytlu'oi'vtorrhe\is,  13() 
Erythrocyto.schisis,  136 
Mther.  i)oisoning  by,  2S 
I'.tlunocephalia.  515 
i'thmoid  bone,  osteoid  sarcoma  of,  435 
I'^thyleu'liamin,  38 
Etiology,  I 
Eumycetes,  40 
Eurotium,  680,  683 

ma  lignum,  680. 
I'Aistronsylus  gigas,  740 
Invent  rat  ion,  521 
|]\enrephalus,  51  1 
I'xhaustion    due   to   excessive    functional 

activity  of  an  organ.  6 
ICxostosis,  265,  394,  532 

cartilaginous,  395 

connective-ti.ssue.  395 
Ex.strophia  intestini,  521 

vesicae  urinaria',  521 
Extravasate,  1.58 
Extravasations  of  blood,  15S.  212 
Extremities,    defective    developnu-nt    of, 
525 

dupUcation  of,  532 
Exudate,  cellular,  326 

croupous,  332 

fibrinopurulent,  341 

fibrinous,  3.32 

luemorrhagic,  337 

purulent,  340 

serofibrinous,  33"Jr 

seroj)urulent,  341 

serous.  331 
Exudates,  ah.snrption  of,  346.  361 
Exurlation.  :'.20 
I'.ye,  regeneration  processes  in.  ;;(t7 


.\CE,  malformations  of,  517 
acial  hemiatrophy.  1S9 
acies  leontina  m  leprosy.  651 
acultative  anaerobes,  551 
allopian  tube,  dropsy  of  the. 
arcy,  654 
a.stigimn.  92 
at-emboli.sm.  67 
at-granule  cells,  197 
atigue,  7 

'at,s.  the,  197,  2():5 
at-synthesis,  197 
at-tissue,  atrophy  of    193 

new  formaticjn.  295 
at-transportalion.  201 
at ty  degeneration.  19S 

deposit,  193 
avus,  41.  685 


2f.O 


766 


GENERAL    INDEX. 


Febris  continua,  92,  709 

intermittens,  92 

malariaformis,  712 

quartana,  707 

quotidiana,  707 

recurrens.  92 

remittens,  92 

subcontiniui,  92 

tertiana,  707 
Feet,  abnormal  positions  of,  .'v2o,  .ViO 
Felt-louse,  752 
Femur,  absence  of,  527 
Fermentation,  556,  557 
Femients,  diastatic  and  iuMTting,  o.'A) 

glycolytic,  81 
Fever,  90 

bactericidal  action  of,  ]  10 

l)lack,  69S 

hlackwater,  711 

cachectic,  698 

continuous,  92,  709 

etiology,  93 

intermittent,  92 

malarial,  the  cause  of,  707 

nature  of,  95 

relapsing,  94,  693 

remittent,  92 

scarlet,  705 

stages,  91 

subcontinuous,  92,  709 

tvphus,  705 

yellow,  cause  of,  614,  699 
Fibrillated  connective  tissue,  develi>pniont 

of,  291 
Fibrin,  136 
Fibrin-ferment,  137.  142 

membrane,  140 
Fibrinogenic  substance,  13S.  142 
Fibrinopurulent  exudates.  341 
Fibrinous  deposits,  332 

exudates,  332 
Fibro-adenoma,  447 

conversion  of,  into  a  caicinouia,  464 

intracanaHcular,  447 

papilliferum,    447 

pericanaUcular,  386,  447 
Fibroblasts,  292,  351 
Fibroepithelioma,  papillarv,  442 
Fibrolipoma,  389 
Fibroma,  385 

intracanalicular(\  447 

multiple,  387,  416 

(edematous,  386 

papillare,  442 

pericanaliciilare,  386.  447 
Fibromatosis  of  the  nerves.  417 
Fibromyoma,  411 
Fibromyxoma,  387 
Filirosarcoma,  423 
Filaria  bancrofti,  160,  269,  747 

ha>matica,  747 

lia-morrhagica,  748 

uu'cliin'usis.  746 

inulli|);ipillosa,  748 

liajiillosa,  747 

sanguinis  hominis,  166,  746 
Fingers,  dwarfing  of,  .528 


Fingers,  nuilformations  of,  528 

multi))Uc:itioi!,  .532 
Fiiikler-Prior  spirilla.  674 
Finsen  light-treatment.  10 
First  intention,  repair  by,  357 
Fish-poisoning,  19 
Fi.ssion-fungi,  549 

methods  of  examining.  5()() 

pathogenic,  558 
Fissnra  alidoniinalis.  520 

al)duinina!is  intestinalis,  521 

genitalis,  .321 

sterni,  .521 

vesicse  urinaria?,  521 

vesico-intestinalis,  ,521 
Fistula  colli  congenita,  518 
Fistulous  tracts,  340 
Flagella,  550 
Flagellates,  691,  693 
Flat  foot,  530 
Flea,  or  pulex  irritans,  753 
Flermning's  germ-centres,  298 
Fleshy  moles,  406 

wart,  406 
Flies,  biting  (CEstrid*),  753 

blow  (Muscid:r\  754 

bot  (nCsiii.h.  .,  7.5:; 

common  ,  ^i  .muixyiiUe"),  753 

.stinging  uMuscida?),  753 
I'^oamy  liver,  605 

organs,  605 
Fo?tal  glands,  persistence  of,  487 

glands,   remains,   development    of    a 
cancer  from,  465 
Foetus  papyraceus,  541 

syphilitic  infection  of,  by  eitlicr  tlie 
sperm  or  the  ovimi,  648 
Food,  effects  of  lack  of,  5 
Foot-and-mouth  di-sease,  114,  585,  670 
Foot,  cleft,  528 

Foods,  poisoning  by  spoiled,  19 
Foot-itch  of  chickens,  751 
I'oreign  body  in  inflammation.  364 

in  cyst,  260,  353 

in  giant-cell,  .353 
Formative  cells,  292 

stimuli,  277 
Im.wIs,  typhoid  of.  669 
l-'ragmentation,  283 
Freckles,  239,  406 
Freezing,  effects  of,  9 

gangiene  due  to,  179 
Friedlander's  pneumobacillns,  (IDii 
Frog  foetus,  513 
Fuchsinophile  bodies.  224 
Fungous  granulations,  369 
Fungus  medulla ris,  373 
Furuncle,  580 

Gadinix,  38,  557 

(lall-ducts,  adenocvstoma  of,  449 

Gall-stones,  234 

Gamba  fever,  697 

Ganglion-cells,  neu-formation  of,  303 

Gangrene,  178 

black,  178 

dry,  178 


(;KM:ir\L   i\i)i.\, 


( langronc,  oniphyvseiiiaiinis,   171,  (iOS 

due  to  tVoeziiifi,  17'.> 

due  to  heat.  179 

infectious,  179 

inarasmic,  179 

moist,  17S 

neuropatWc,  179 

pressure,  179 

putrid,  178,  34.5 

senile,  179 

symmetrical,  179 

toxic,  179 

white,  178 
Gangrenous  iufl:unmation,  345 
Gas,  irrespirable.  23 
Gas-phlegmon,  604 
Gastropachia  pini,  687 
Gastrophilus  equi,  754 

ha?morrhoidalis,  754 

peconmi,  754 
Gastroschisis,  520 
Genitals,  external,  development  of,  53S 

malformations  of,  523 
Germ-centres  of  Flemming,  29S 
Germ-sac,  primary,  716 

.secondary,  7 16 
Germ-variation,  primary.  .58.  499 
Germinal  anlage,  misplaced.  485 
Germinal  tiansmission  of  disease,  61 
Giant -crll  <arcoma,  423 
Giant-cells,  283,  353 

embolism  of,  69 

foreign  body,  353 

in  tubercles,  618 

raultinuclear,  283,  353 

plasmodial,  283 

syncytial.  284 
Giant  growth,  general,  49,  262,  531 

growth,  partial,  262,  531 
Giants,  49,  255 
Giraldes.  organ  of,  538 
Gland-activity,  cessation  of,  79 
Glanders,  654 

Glia-cells.  new-formation  of,  304 
Glioma,  413 
Gliomatosis,  415 
Gliosircoma,  414 
Globulicidal  antil)odies,  105 

senmi,  120 
fJlossina  morsitans,  697 

palpalis,  697 
Glycogen,  204 
Glycosuria,  79 

Gnats  (("uhcidse  and  Tipulida:>),  753 
Goblet-cells,  207,  453 
Goitre,  84 

exophthalmic,  85 
Gonococcus,  582 
Gonorrhoea,  cause  of,  582 
Gout,  49,  77,  231 
Gouty  deposits,  77,  232 
Granula,  241 

Granular  degeneration,  190 
Granulation  tissue,  347,  353,  354 

formation  of,  354,  359,  363 
Granulations,  chronic,  368 

fungus,  369 


<iranulalion  tumors,  infer' ions,  :U>S 

(Iranules.  liyaline.  224,  225 

(iraimioma,  coccidioidal.  6.S2 

(iranulomata.  369 

Grape-mole.  465 

Gras.s-bacilli,  621 

Gravel,  235 

Graves'  dist-asc,  ,S5 

(Ireciiish    color.il imi    in    .JccoMiposinL'   cn- 

dav.Ts.  170 
(Irossainmcn.  716 
Ground  itch,  73S 
(Irowtli.  causes  of.  277 
Guinea-worm,  746 
Gunnnata,  M.'y 
Gynax'omastia,  .534 

H.EM.VNOIU-ENDOTHKI.IOM  A.     102,    129 

Ha>mangioma,  398 

cavernosum,  410 

liypertrophicuiii.  412 

plexifornic.   102 

simjjlex,  39,S 
HaMnangiosarcomata.  4:51 
HaMiiangiotic  endothelioma.   162,  432 
Ha'mateinesis,  158 
Iheniatidrosis.  1.58 
Iheniatocele.  1.58 
Ihenialochyluria,  717 
Ha-matoidin,  243 
Ha'matoma,  1.58 
Ha'inatometra,  1.58 
HaMuatomonas,  695 
Ha>maturia,  158 
Ha-mochroniatosis,  242.  247 
Ha-mofuscin,  238,  240 
Ha>ni()gl()i)in,  243 
Ha'inogl()i)ina'mia.  2J(; 
HaMnogl()l)inuna,  216 
Ha'molysin.  25.  120 
Ha'inolvtic  poisons,  25,  26 

sera,  105 
Ihemopericardium.   158 
lhrm()i)liilia.  60,  150 

ac(|uired,  160 

congenital.  50,  160 

of  cattle,  712 
Hfemoproteus  noctuic,  698 
Ha^moptoe  or  iia'moptj'sis,  1.58 
Ha'morrhage,  1.58,  23(> 

diabro.sin,  159 

diapede.sin,  159 

rhexin.  1.59 
Ila-morrhagic  enteritis.  .5S7 

se|)tica'mia,  6(»S 
HaMuosiderin,  244 
Ila'inosiden.sis,  247 
Iheinosporidia,  707.  711 

Ihe thorax.  1.5S 

I  lair-fungi.  .5.50,  665 

Hairs  in  dermoid  cvsl-.   ISO.   I'.Mi 

Hairy  polypi.  495  " 

tongue,  213 
llalteridium.  69S 
Hand,  cleft,  .528 

clubbed.  .530 

malformations  of,  .525 


"GS 


GENERAL    INDEX. 


Hands,  abnormal  positions  of,  529 

Hanging-drop  cultures,  562 

Haptins,  39,  120 

Harelip,  517 

Harvest-mite,  752 

Hay-fever,  46 

Head,  malformations  of,  513 

Head-louse,  752 

Healing  by  first  intention,  357 

by  second  intention,  357 

powers  of  the  human  body,  108 

serum,  113 
Heart,  action  of,  124 

disturbed  action  of,  125 

fibroid  area  in,  363 

increased  action  of,  127 

valvular  lesions,  126 
Heart-musolo.  rompensatorv  hypertrophy 
uf.  r_'7,  267 

liyijcrtrophy  of,  127 

jngment  of,  246 

rigor  mortis  of,  170 

tiger,  201 
Heart  poisons,  2<S 
Heart-]  (111  vpi,  145 
Heat-fxli:iustion,  8 
Heat-stroke,  8 
Helcosoma  tropicum,  699 
Helleborin,  poisoning  by,  29 
Helvellic  acid,  poisoning  by,  26 
Hemiatrophy,  congenital,  189 

facial,  189 

infantile,  189 
Hemicrania,  514 
Hepatitis,  cln-onic,  370 
Hereditary  pieces  or  determinates,  60 
Hereditary  transmission,  atavistic,  55 

collateral,  55 

direct,  54 

pseudo-form  of,  61 
Hereditv,  degenerative,  54 

ideiitical.  54 

tlieories  concerning,  55,  56 

transformational,  54 
Hermaphrodism,  false,  535 

true,  535 
Hernia  basalis,  515 

cerebri,  514 

funiculi  umbilicaUs,  520 

lateralis,  515 

nasoethmoidaUfi,  515 

na.sofrontalis,  515 

nasoorbitalis,  515 

occipitalis,  514 

sphen()or!)itaUs,  515 

spiuMionuixillaris.  515 

sphciiopharyngea,  515 

svHcipilalis,  515 

u"nibilic;.l,  520 
Ih'rpes  tonsurans,  41,  685 
llerpetomonas  lewisi,  695 
Herpetosoma,  695 
ileterakis,  736 

Heterotopous  tissue-growths,  485 
Hexainitus  duodenalis,  692 
Histoid  tvnnors,  372 
Ilog-choleia,  668 


Holorachischisis,  508 

Holoschisis,  280 

Homo  delinquens,  50,  55 

sapiens,  51 
Hook-worm,  737 
Horn,  cutaneous,  264,  141 
Horny  warts,  264,  441 
Horse-flies  (Tabanidse),  753 
Humerus,  osteochonflroma  of,  397 
Hunteriaii  induration.  642 
Hvahii,  connective-tissue,  222 

epithelial,  209 

exudative,  225 
Hyaline  cartilage,  reproduction  of,  293 
Hyaline  degeneration,  222 

of  connective  tissue,  222 

of  connective  tissue  of  heart,  223 

of    connective  tissue    of   vessel-wall, 
223 
Hyaline  exudations,  225 

products    of    connective-tissue    cells, 
224 

thrombi,  225 

tissue-necrosis,  225 
Hydatid  mole,  465 
Hytlatids,  727 
Hydrencephalocele,  514 
Hydrocele  colli  congenita,  519 
Hydrocyanic-acid  poisoning,  25 
Hydrogen-sulphide  poisoning,  25,  26,  76 
Hydronieningocele,  510 
Hydromyelocele,  510 
Hydropic  degeneration,  192 
Hydrops,  151 

adiposus,  156 

chyliformis,  156 

chylosus,  156 
Hydroracliis,  508 
Hydrothorax  chylosus,  166 
Hygroma  colli  congenitum,  405 
Hyoscyamine,  poisoning  by,  28 
Hyperaemia,  active,  130,  131 

local,  130,  131 

passive,  131 

venous,  general,  125,  131 
Hyperkeratosis,  213 
Hypermastia,  534 
Hyperonychia,  264 
Hyperostosis,  367 
Hyperparathyreosis,  85 
Hyperplasia,  262,  285,  367,  369 
Hyperpyrexia.  91 
Hvpersusceptihility,  122 
Hyi'fi-tlu-lia,  534 
Hvpcrthvrcosis,  85 
HypertriVhosis,  264 
Hypertrophy,  262 

compensatory,  127,  268 

due  to  lessened  use,  268 

due  to  non-resolution,  2(58 

due  to  over-work,  7,  267 

due  to  removal  of  pressure,  269 

inflammatory,  269 

of  a  muscle  or  gland,  7,  447 

of  the  tissues  and  on!;ans,  262,  2()5, 
267 
Hyphffi,  40,  678 


(IKNKKAI.     INDKX 


7<i'.» 


Hyplu.niycvtrs.  :,M).  (.77 
Hypi)rlu)U(lri;i,  IS 
]lvi)()tl(M-ina  l)()vis.  7.")  I 

iliana.  7.')4 
Hypophysis,  8.') 
Hypoplasia,  180 
Hvposarca,  151 
uVpospadias,  o-J.S 
Hypostasis,  133 

post-mortem,  132,  169 
Hypostatic  coiifrpstion.  133 
Hysteria.  IS 

liHTHYOSIS,  263 

fonjioiiita,  2(i3,  264 

hystrix,  264 
•lithyotic-  warts,  264,  44U,  441 
•hthyotoxin,  20 
•terus,  251 

neomitorum.  251 
liosyncrasy,  46 
iimuiK--l)ody,  1];» 
ninvme-sera,  1 1(1 
lininuuity,  44,  45,  90 

actiuiring  of,  111,  118 

active,  113 

against  poisons,  99,  US 

Ehrlich's  theory  of,  118 
Immunization,  active  and  passive,  IK] 
Implantation,  309,  312,  486,  496 

bigerminal,  496 

monogerminal,  496 
inai'tivity.  I'ffects  of,  7 
Inchisio  tVetalis,  547 
Indolent  ulcers.  368 
Induration.  Hunterian.  642 
Infarct,  amemic,  163 

emboUc,  164 

lia?morrhagic,  158,  16:3 

liealing  of,  164.  362 
Infection,  30,  39,  559 

by  means  of  animal  parasites,  42 

cryptogenic,  37,  573.  580 

double,  38,  559 

hiematogenous,  36,  37 

ins(>cts  as  conveyers  of,  43 

intra-utcrine,  37,  559 

Ivmphogenous,  36.  37 

taetasfatie.  36,  37 

mixed,  :;s 

oriiriii  of  disease  through.  30 

protection  against,  100,  1  1  1 

secondary.  3S.  r,:,\).  635 

spread  of,  bj'  nios;|uitos.  44.  712.  7.' 

.spread  of,  from  mother  to  f(etus,  :', 
61,  559 
Infectioiis  diseases,  30 

healing  of,  108 

inheritance  of,  37,  61 

local,  35 
Infectious  foci,  metastatic,  3() 
Infiltration,  326 

growtli  of  tumors  by.  :>S0 

purulent,  340 

serous,  331 

small-celleil.  339 
Infiltrations  of  the  tissues.  IC.7,  320 
49 


lnfillrali\ 


growth 


arci 


480 


luManuMatioii.  .ill) 

catarrhal.  3:51.  3  1(1 

ciuoiiic.  365 

clinical  signilicaiice  ..f  lii.'  iridi    S'.'. 

croupous.  .3.33 

ditVcrei.t  forms  of.  :',:',\ 

dipiitheritic,  344 

excretory,  320 

fiiirinou.s.  332 

intenstitial,  328 

metastatic,  320 

necrotic,  343 

parenchymatous.  .329 

purulent.  :!40 

superficial,  329 

sup|)urative,  340 

termination  of,  345,  ;!47 
Influenza-bacillus.  ()07 
Infu.soria.  715 
Inheritance   of    pathologic;d    ipcculiarilies. 

Initial  sclerosis,  642 

Injection  of  sterilized  cullnres.   I  11' 

limervation,  ilisturbaiices  of,    |6,    17     77 

1 29 
Inoculation,  1 1 1 
Inoculation  of  attenuated  specific  disea>e- 

germs,  1 1 1 
Insanity,  inherited,  .")(),  54 
Insect a,  752 
Insects,  43,  752 
Insolation.  8 

Insusceptibility  to  poisons.  40 
Intermediate  boily,  119 
Intermittent  fever,  92 
Internal  .secretion.  79 

secretion,  disturbances  of.  75.  79 
Interstitial  infianunation,  32N 
Intestinal  intoxications,  35 

nmcous  membrane,  adenoma  like  pm- 
jectitm  of.  487 
Intestine,    abnormal     positions     of,     5_'0. 
530 

tul)ular  adenoma  of,  4  1 1 
Intoxication,  ba<)eri;il,  35 
Intoxication,  origin  of   disea.ses    through. 

18,75 
Invasion-disease.  45 
Inversio  intestini.  521 

vesica'  urinaria-,  521 
lodothyrin.  84 
Irfni,  a.ssiiiiilation  of,  249 

content  of  foods.  6 

deposit.  256 

insufficiency  of.  6 

reaction,  24  1 
Iron-free  pigments,  213.  219 
Irradiation.  10,  14 
Iscluemia,  localized,  133 
Ischiopagus.  541 
Isolysin.  120 
Isotricha  prostoma.  715 
Isthmus,  the.  of  aorta.   127 
Itch-mite,  748 
Ixodes  ricinus.  750 


770 


GENERAL    INDEX. 


Janiceps,  543 
Janus-head,  543 

Jarrings  of  the  uterus  as  a  cause  of  mal- 
formations of  the  embryo,  499 
Jaundice,  251 
Jaw,  actinomycosis  of  upper,  662 

giant-cell  sarcoma  of,  424 

lower,  absence  of,  518 

Kakerlaken,  257 

Kakke,  19 

Kala-azar,  698 

Karyokinesis,  280 

Karyolysis,  171 

Karyomitosis,  280 

Karyorrhexis,  171 

Kedani  disease,  751 

Keloid,  387 

Kepliir,  588 

Kephir-ferment,  588 

Keratin,  212 

Keratohyalin,  212 

Keratosis  follicularis,  705 

Ividney,  amyloid  degeneration  of,  218 

arteriosclerotic  atrophy  of  the,  188 

cloudy  swelhng  of,  191 

compensatory  hypertropliy  of,  287 

contracted,  370 

cystoma  of,  450 

deposits  of  fibrin  in  the,  33" 

senile  atrophy  of,  188 

streptococcus  infection  of,  572 
Kinetoses,  18 
Klasmatocytes,  299 
Kribbelkrankheit,  23 
Krumelzellen,  354 
Krystallwulst,  307 

Labia  majora  and  minora,  defective  de- 
velopment of,  524 
Labium  leporinum,  517 
LambUa  intestinalis,  692 
Lardaceous  degeneration,  214 

spleen,  214 
Larynx,  papillary  epithelioma  of,  441 

syphiHtic  ulceration  of  the,  647 
Latency  of  disease,  1 
Lead,  deposit  of,  256 
Lead-poisoning,  23 
Leiomyoma,  409 
Leishmani  donovani,  699 

infantum,  699 

Wright i,  699 
Lens,  regeneration  of,  307 
Lentigines,  230,  409 
Leontiasis  ossea,  265,  532 

leprosa,  651 
Lepra  (or  leprosy).  649 

ana^sthetica,  653 

maculosa,  753 

mutilans,  653 

nervorum,  652 

nodosa,  652 

tuberosa  sive  tviberculosa,  652 

ulcerosa,  652 
Leprosy,  649 

white,  of  the  Jews,  258 


Leptothrix,  540 
Leptus  autumnalis,  750,  752 
Leucocytes,  106,  110,  298,  321.  339.  SM, 
351 

emigration  of,  321,  324 

marginal  disposition  of,  321 

new-formation  of,  298 

varieties  of,  298 
Leucocytha^mia,  298 
Leucocytosis,  298 
Leucoderma,  258 
Leuconostoc  mesenterioides,  564 
Leucopathia  acquisita,  257 

congenita,  257 
Leucotrichia,  257 
Leuka?mia,  298,  682 
Leydenia  gemmipara,  690 
Lice,  752 

Life-trophoblasts  or  biophores,  60 
Light,  effects  of,  10,  14 

influence    of,    upon    tlevelopment    ot 
bacteria,  551 

ultraviolet,  10 

violet,  10 
Lightning  figures,  15 
Lightning-stroke,  14 
Lime-salts,  deposit  of,  226 
Linguatulidse,  748 
Lip,  carcinoma  of,  461 

malformations  of,  517 
Lipochrome,  238,  240 
Lipofibroma,  389 
Lipoma,  389 
Lipomatosis,  49,  194 
Lipomyxoma,  389 
Liquefaction-necrosis,  176 
Lithocelyphopsedion,  507 
Lithocelyphos,  507 
Lithopsedion,  506 
Liver,  abscess  of,  690 

amyloid  degeneration  of,  215,  217 

angioma  cavernosum  of,  399 

chronic  inflammation  of,  370 

cirrhosis  of,  370 

coccidia  disease  of,  701 

corset,  189 

cystoma  of,  449 

foamy,  605 

gumma  of,  646 

hypertrophy  of,  287 

multilocular  adenocystoma  of,  450 
Liver-fluke,  716 
Livores,  132,  169 
Lucilia  macellaria,  753,  754 
Lungs,  actinomycosis  of  the,  661 

fibrinous  exudates  in  the,  337 

induration  of,  367 

mould-fungi  in  the,  679 

red  hepatization  of  the,  337 

syphilitic  disease  of  the,  648 

tuberculosis  of  the,  617,  619.  628.  629, 
631,632 
Lupus  of  the  skin,  626 
Luxations,  congenital,  529 
Lymph,  antibacterial  properties  of,  102 

formation  of,  151 

hindrance  to  flow  of,  154 


GENKKAL     INDKX, 


771 


Lymphadonoid  tissue,  roproduction  of,  2'.t.'i 
Lynipluriiiia,  _",IS.  43(5 
Lymphaii!:;ii)c-iulotlielioma,  42o 
Lyniphaiijiionia.  404 

cavenuKsuni,  404 

cystoiilos,  404 

hypertrophicum,  40.'> 

simplex,  404 
,|  Lymphangiosareoina,  42."> 

Lymphan<xoiti.s,  37 
Lyniphatie  constitvition,  89 
Lymph-fistula,  166 

LJ^^pll-glands,  action  of,  as  filters,  102 
Lymphocytes,  322.  350,  3")1 
Lymphorrhasia,  16.3 
Lympliosarcoma,  421,  43(> 
Lymph-vessels,  new-formation,  2'.HJ 
Lysis,  in  fever,  92 
Lysogenous  substance  of  Frankel.  109 

Macrocheilia,  405 

Macrogamete,  704,  710 

Macroglossia,  405 

Macrostomia,  518 

Madura  disease  or  Madura  foot,  665 

Maidismus,  41 

Malanders,  751 

Malaria,  707 

forms  of,  708 

in  animals,  711 

pigment  in,  249 

Plasmodia  of,  708 

the  cause  of,  708 
Malformations,  498 

congenital,  498 

etiology,  499 

varieties,  503 
Maliasmus,  654 
Malignant  oedema,  604 

timiors,  384 
Mallein,  656 
Malleus,  654 
Mai  perforant,  179 
Mammary  gland,  adenoma  of,  445 

carcinoma  of,  470,  471,  472 

endothelioma  of,  426 

intracanalicular  fibroma  of.  447 

mucous  carcinoma  of.  473,  474 

papillary  cystocarcinoma  of,  464 

papillary  cystoma  of,  454 

tubular  adenoma  of,  464 
Marasmic  thrombi,  145 
Marasmus,  8,  165 
Margarin  crystals,  203 
Marginal  disposition  of  leucocytes,  321 
Mast-cells,  225,  354 
Mastigophora,  691 

Mastoid  antrum,  cholesteatomata  in,  443 
Measles  of  teeniae,  721,  724 

of  trichina,  745 
Meat-poisoning,  19,  35,  587,  600 
Meckel's  diverticulum,  521 
Mediastinal  dermoids,  486 
Medullary  cancer,  472 
Megastoma  entericum,  692 

intestinale,  692 
Mela?na  neonatorum,  160 


Melanin,  2,38,  240 
Melanoinata,  405 
Melanosarcomata,  4.3.3 
Melanosis  of  internal  organs,  211 
Melasma  suprarenale.  .S7 
Membrane,  pyogenetic,  3(»4 
Meningitis,  «'pidemic  ciTebrnspin.il.  .■)77 
Meningocele,  .")()9.  51  I 
Meningococcus,  577 
Meningo-ence|)iialitis  syphilitica,  (111 
Meningo-enceplialocele",  514 
Menorrliagia.  I.'xS 
Merismopcdia,  549,  5.')0,  5(k3 
Merorachiscliisis.  .lO.S 
Merozoites,  701,  704 
Mesodermal  cpitlielial  cysts.  I.S(> 
Metabolism,  bacterial,  .").')() 
Metaglol)ulin,  142 
Metakinesis,  281,  282 
Metamorj)hosis,  viscovis.  140 
Metaplasia,  epithelial,  3 IS.  ."),S3 

of  the  tissues,  314 
Metastasis,  64 

direct,  65 

formation  of,  in  carcinoiuaia,   '57 

ha>matogem)us.  64 

in  tulxTculosis.  632 

lymphogenous,  64 

of  dust,  65 

of  parasites,  69 

of  parenchymatous  cells,  67 

of  pigment,  69,  70.  242.  245 

of  placental  cells,  ()7 

of  soluble  substances.  (\U 

paradoxical,  65 

retrograde,  65 
Metastatic  daughter-tumors.  (iS.  ;;,s0 

infectious  foci,  6!) 

inflammations,  64 
Met  haemoglobin,  246 

the  formation  of.  2() 
Metlia?moglobinuria.  24(5 
Methyl  guanidin.  33 
Metrorrhagia.  15S 
Miasm,  definition  of.  30 
Miasmatic-contagious    disea.se,    definition 

of,  30 
Miasms  and  contagions,  boundary-line  be- 
tween. 31 
Micrencephalon,  .50.  1S2 
Micrencephalus.  182,  514 
Microt)acleria,  549 
Microbraciiius.  .')25 
Microcei)halus,  IS2.  514 
Micrococci,  549,  5().3 
Micrococcus  ascoformans.  .585 

aurantiacus,  564 

botryogenes,  585 

cyaneus,  .")()4 

gonorrhoea",  582 

haematodes.  .564 

in  meningitis,  577 

in  mycofibroina,  .').S5 

in  myco.sis  of  parrots,  .").S5 

in  pseudotuberculosis  of  guinea-pigs, 
.585 

lutcus,  564 


GENERAL    IXDEX. 


Micrococcus    of    foot-ancl-muuth    ilisoa.se, 
585 
of  hsemoglobiniiria  of  cattle,  585 
of  lung-disease  of  horses,  585 
of  strangles,  585 
pathogenic,  564,  565 
pyogenes,  578,  584 
tetragenus,  564 

tetragenus  of  udder-disease,  585 
urese,  564 
violaceus,  564 
viscosus,  564 
xantogenicus,  614 
Microgamete,  705,  710 
Microgametocyte,  704,  710 
Microgyria,  182 
Micromelus,  525 
Micromyelia,  50 
Microproteins,  34 
Micropus,  525 
Microsomia,  506 
Microsporon  furfur,  686 
miiiutissinium,  686 
Microtomia,  518 
Miescher,  sacs  of,  703 
Miliary  tubercles.  618,  625,  633 

tuberculosis,  hsematogenous,  633 
Milk  from  tuberculous  cows,  638 
Mineral  poisons,  19 
Miracidium,  716 
Missed  labor,  507 
Mites,  748,  751 
Mitosis.  280 
Mole,  405 

fleshy,  406 
hairy,  405 
hydatid,  465 
pigmented,  239,  405 
MoUer's  or  Barlow's  disease,  160 
MoUuscum  bodies,  703 
Monilia  Candida,  681 
Monol)rachius,  525 
Mouocercomonas  liominis,  692 
Monogerminal  tissue-implantation,  496 
Monomorphous  bacteria,  538 
Monopus,  525 
Monsters,  498 

double,  504,  539 
single,  506 
triple,  540 
Morbus  Addisonii.  87,  231 

maculosus  Werlhofii,  160 
Morgagni,  hydatid  of,  538 
Morphine,  poisoning  by,  28 
Morphoea  nigra  et  alba,  653 
Mosquitos,  agency  of,  in  spreading  certain 

diseases,  44,  712,  753 
Mother-star,  280,  282 
Mould-fungi.  40.  678 
Moulds,  677.  685 
Mouth,  development  of,  519 

malformations  of,  518 
Mucins,  the,  208 
Mucor  corymbifer,  680,  682 
pusillus,  682 
ramosus,  682 
rhizopodiformis,  682 


Mucous  degeneration,  207 

membranes,  carcinoma  of,  461 
membranes,    papillarj-   epitheliomata 

of,  441 
tissue,  reproduction  of,  295 

M tiller's  duct,  538 

Multiple  fibromata  of  the  skin,  53,  417 

Mummification,  178 

Musca  anthropophaga,  754 
vomit  oria,  754 

Muscardine  in  silkworms,  687 

Muscarin,  poisoning  by,  29 

Muscidse,  754 

Muscle,  atrophy  of,  187 

heart,  hypertrophy  of,  267 
heart,  new-formation  of,  302 
in  dermoid  cysts.  491 
non-striated,  hypertrophy  of.  302 
non-striated,  new-formation  of.  302 
striated,  hypertrophy  of,  302 
striated,  new-formation  of,  300 
waxy  degeneration  of,  1 75 

Muscle-trichina.  744 

]Muscles.  cadaveric  stiffening  of,  169 
supernumerary,  534 

Mviscular  svstem,  pathological  changes  iu 
the,  50 

Mussel  poisoning,  20 

Mycelium,  678 

Mycetoma,  665 

Mycobacterium  tuberculosis,  621 

Mycoderma  albit-ans,  681 

Mycodermoid,  585 

Mycofibroma,  585 

Mycoprotein,  550 

Mycosis  of  alimentary  tract,  679 
of  respiratory  tract,  679,  680 
of  skin,  685 
versicolor,  686 

Mycosozin,  104 

Myeljpmia,  298 

Myelocele,  510 

Myelocystocele,  509 

Myelocystomeningocele,  510 

Myelocysts,  487 

Myeloma,  422 

Myelomeningocele,  509 

Myiasis,  754 

Myofibroma,  411 

Myoma,  409 

Isevocellulare,  409 
striocellulare,  411 

Myosarcoma,  412 

Myositis  ossificans,  50,  397 

Myxoangiosarcoma,  437 

Myxoedema,  83 

Myxofibroma,  387 

MyxoUpoma,  387 

Myxoma,  387 

Myxosarcoma,  387,  424 

N.^VUS    FLAMMEUS,  399 

lymphaticus,  405 
pigmentosus,  405 
pilosus,  405 
prominens,  400.  405 
spilus,  405 


(iKXKHAI,     INDIA 


Na-vusvasfulosus.  M*t'l.  tOO 

verrucosus.  400.  40."> 

viuosus,  300 
Nagana,  607 
Nanosomia,  306 
Nasal    mucous   luonihranc.    Ivniphosarfo- 

ma  of.  421 
Navel  stone,  234 
Xecator  aiiiericanus.  73.S 
Neck,  nialfoniiations  of,  .')I7 
Xeci'obiosis.  172,  17.) 
Necrosis.  170 

anapmic.  172 

cheesy,  17,> 

coagulation.  174 

colli  quat  ion.  176 

decubital.  173,  170 

direct,  172 

indirect,  172 

liciuefaction,  176 

niarasmic,  173 

nuimniifying,  178 

neuropathic,  173,  170 

sequelae  of,  173 

senile,  170 

thermal,  171,  170 
Negri  bodies,  705 
Nemathelminthcs.  734 
Xematoda,  42.  734 
Nematodium  o\-is  pulmonalis,  740 
Neoplasm,  371 
Nerve-  and  heart-poisons,  27 
Nerve  elements,  new-formation  of,  303 
Nerve-fibres,    peripheral,    new    formation 
of,  304,  307 

peripheral,    pathological    changes   in, 
.51 
Nerves,  fibromata  of.  417 

fibromatosis  of.  .51,  417 

leprosy  of,  652 

regeneration  of.  305 
Nervous     system,     central,     pathological 

changes  in  the,  50 
Neurasthenia,  IS 
Neuridin,  33,  38,  557 
Neurin,  33,  38,  557 
NeuroepitheUoma,  415 
Neurofibioma,  417 
Neurogha,  hypertropliic  growth  of.  301 

regenerative  growth  of,  304 
NeurogUoma  ganghonare,  414 
Neuroma,  416 

amputation,  306,  416 

amyehnicum,  418 

cirsoid,  417 

ganghon  collularc  vcniiii.  418 

myclinicum.  41  7 

jjlcxiforme.  417 

vcruin,  418 
Neuropathic  atrophy.  1X0 

gangrene,  170 

necrosis,  173 
Neuroses,  traumatic,  17 
Neurotization,  306 
Nicotine,  poisoning  by,  20 
Nitrate-of-.silver  poisoning,  23 
Nitrobacteria,  557 


Nitrogenous  nourisluneiit,  iinp<irt:ui 
Nitrous  oxide,  |)oi.snning  by.  JS 
Nodes,  gouty,  232 
Normal  .sennn.  I  ].'< 
Nuclear  contents.  2S0 

framework.  278.  2S0 
Nuclear  divi.sioii,  asymiiictricni.  2.v. 

atypical,  2S2 

ilirect.  276.  2S0 

indirect.  28.3 

pluripolar.  2.S2 


spindle.  2S1 
Nucleinic  acid.  105 
Nucleus,  composition  of  ilic.  2S0 
Nutrition,  retrograde  dist  iu-b:in<'fs 
Nvktothenis  faba.  715 


Orksitv.  40.  104 

diabetogenous,  ,S0 
Obligate  anaeroi)es.  551 
Obturating  throminis.  145 
Ochrono.sis  of  cartilage.  241 
Odontoma,  304 
(Edema  and  dropsy,  151 

cadiectic,  155 

collateral.  1.55 

due  to  arterial  congestion.  154 

due  to  ol)structioii  of  thoracic 
154 

ex  vacuo.  156 

hydra'mic.  1.55 

inflanunatory,  155.  331 

mahgnant,  604 

purulent.  341 

stagnation.  1.54 

varieties  of.  154 
(Esophagus,  growth   of  thrusli   iipo 

670 
(EstridiT*.  7.53 
(Estrus  bovis.  754 

ovis,  754 
Oidiiun  albicans,  1581 

coccidioides.  (W2 
Oidiomvcosis,  41.  ()S2 
Olein.  203 

( )ligomorphous  !)acteria,  510 
Omentvun,  tuberculosis  of,  6|8 
Oinpludoceie.  .520 
( )inphalome.senteric  cvst .  .522 

duct.. 521 
()n>plialoi)agus.  517 
()ncos|)ha'ra,  733 
Onycliogryphosis.  264 
( )nvchomvc<'sis  favosa.  0X5 

■  triciiophvtina.  6X6 
Oocy.st,  701.  704.  710 
Ookinete.  710 
Oophorin.  80 

Ophryoscolex  caudatus.  715 
Opium  an<l  morpliine.  poisoning  liy. 
Opsonic  ind<'\.  HMi 
Opsonins,  105 

Organization  of  thrombi.  I  IX 
( )rgans,  weight  of.  26li 

volume  of,  2<56 
O.ssification.  220 


774 


GENERAL    INDEX. 


Osteoarthropathie  hyixTtrophiaiite,  270 
Osteoblasts.  292 
Osteochondroma.  393.  396 
Osteofibroma.  396 
Osteoid  sarcoma.  436 

of  ethmoid.  43") 

trabeculse.  437 
Osteoma.  394 

dental.  394 

disconnected,  394 

durnm  sen  eburneum.  394 

heteroplastic.  ,394 

meduUare,  394 

parosteal.  394 

spongiosum,  394 
Osteomyehtis.  569 
Osteophyte,  394 
Osteoporosis,  185. 
Osteosarcoma,  436 
Ovary,  adenocystoma  of.  451 

cystoma  of,  451 

dermoid  cysts  of,  490 

multilocular  adenocystoma  of.  449 

papillary  cystadenoma  of.  451.  453 

papillary  cystocarcinoma  of.  479 

papillary  epithelioma,  440.  442 

teratomata  of,  492 

transplantation  of,  312 
Over-exertion,  7 
Over-heating,  8 

Overwork,  hypertrophy  from.  7.  260 
Oxidation,  intra-organic,  93,  95 
Oxygen,   effects   of   a   diminntion   in   the 
supply  of,  4 

influence    of,    upon    develojunent    of 
bacteria,  551 
Oxyuris  vernucularis.  736 

Pachyakria,  270 

Packet-shaped  cocci.  549.  563 

Paget 's  disease,  705 

Palate,  malformations  of,  517 

Palmitin,  203 

Pancreas,  cyst  of  the,  259 

diabetes  after  extirpation  of,  80 
Papillary  adenomata.  446 

conversion  of,  into  a  carcinoma.  464 

cystomata,  448 

epitheUomata.  440 
Papilloma,  385 
Parachoha,  ?52 

nervous,  252 
Paradoxical  embolism,  65 
Parakeratosis.  208 
Paralysins.  109 
Paramecium  coli,  715 
Paramucin,  208 
Parapedesis,  252 

Parasite  (in  the  case  of  twins).  545 
Parasites,  30,  31 

animal,  689 

ectogenous,  31 

endogenous,  31 

formation  of  cysts  by.  2()() 

metastasis  of,  69 
Parasitic  diseases,  30 

infection,  30,  31 


Parasitic  arthropoda,  43 

protozoa,  42 

worms.  42 
Parasitism,  origin  of  disease  through,  30. 

33 
Paratyphoid  bacteria,  597 

fever,  597,  600 
Parenchymatous  cells,  eml>olism  of,  68 

degeneration,  190 

inflammation.  329 
Parietal  thrombus,  145 
Parosteal  osteomata,  394 
Parotid  gland.  angio.sarcoma  of,  431 

chondrofibroma  of,  431 

chondromyxosarcoma  of,  3Vt2 

myxoangiosarcoma  of,  437 
Parrots,  mycosis  of,  585 
Pathogenesis,  1 

Pathology  and  pathological  anatomv.  the. 
1 

chemical,  2 

clinical,  2 

general,  definition  of,  2 

physiological,  1 

problems  of,  1 
Pearl  disease,  615,  637 

tumors,  442 
Pearls,  epitheUal,  213,  442,  470 
Pediculus  capitis,  752 

pubis,  752 

vestimentorum,  752 
Pellagra,  19,  41 
Penicillium  glaucum,  41 
Penis,  duplication  of,  534 

stunting  of,  523 
Pentastoma,  43,  748 

denticulatum,  751 

tisenioides,  751 
Peptotoxin,  557 
Peribronchitis.  339 
Peripheral    nerves,    pathological    changes 

in,  51 
Perithecia,  683 
Perithelioma,  431 

Peritoneum,  cystic  lymphangioma  of,  405 
Peritrichous  flagella.  603 
Perlsucht,  615,  637 
Pernicious  malaria,  709 
Perniones,  9 
Perobrachius,  525 
Perochirus,  528 
Perodactylism,  528 
Peromelus,  525 
Peropus,  525,  528 
Perturbatio  critica,  92 
Pes  calcaneus,  530 

equinovarus,  529 

valgus,  530 
Pest,  612 

bacillus,  612 
Pestilence,  definition  of,  32 
Petechi£e,  158 
Petrifaction,  226,  507 

in  carcinomata,  476 
Petrifying  sarcoma,  437 
Phagocytes,  98,  101,  346,  352 
Phagocytosis,  97,  101,  346,  347 


CENKHAl.    INDKX. 


I'iialiin,  pi)isoiiiiig  by.  2(i 
Phimosis,  hypertropliic.  ,'y2\ 
Phleboliths.  147,  234 
Phlegmon.  341 

woodt'ii.  573 
Phloridzin  diabetes,  81 
Phocomelus.  52.5 
Phosphorescent  phenomena.  5.58 
Phosphorus  poisoning,  23 
Phthirius  inguinalis,  752 
Physalides.  475 
Physiology,  pathological.  1 
Pia  mater,  cholesteatomata  of  tli(\  443 
Picric  acid,  poisoning  liy.  2(5 
Pigcon-iiiphtheria,  669 
Pigment,  autochthonous.  238 

extrinsic,  255 

ha^matogenous.  242 

metastasis  of,  69 

pathological  absence  of,  257 

pathological  formation  of.  238 
Pigment-atrophy,  185 
Pigment-carrying  cells,  244.  245 
Pigmented  mole,  239,  405 

warts,  239,  405 
Pin  worm.  736 
Piroplasma  bigemimmi,  712 
Pircjuet's  reaction,  622 
Pithead  tapeworm,  732 
Pityriasis,  686 

versicolor,  41,  686 
Placental  cells,  embolism  of,  67 

infections,  intra-uterine,  61,  552 

transmission  of  disease,  61 

villi,    carcinomatous    transformation. 
465 
Plague,  bubonic,  612 
Plasma-cells,  298,  354 
Plasmodiophora  brassicie,  458 
Plasmodium  immaculatum,  708 

malarise,  707 

praecox,  708.709 

vivax,  708,  709 
Plasmolysis.  136,  171 
Plasmorrhexis,  136,  171 
Plasmo.schisis.  136.  171 
Plate-cultures,  561 
Platyhelminthes,  716 
Plerocercoid,  733 
Plethora,  127 

Pleura,  endothelioma  of,  427 
Pleuritis,  fibrinous,  335 
Pleuropneumonia,    contagious,    of   cattle, 
585,  670 

immunization  again.st,  113 
Plexiform  neuroma,  417 
Plimmer's  bodies,  4.58 

Plugs,  ei)itliclial,  in  cancer  of  tiic  skin.  460 
i'luripolar  division,  2S2 
Pneumococcus,  575 
Pneumonia,  croupous,  337,  575.  (KXi 

infectious,  of  cattle,  685 

of  horses,  585 
Pneumotoxin,  577 
Pointed  condylomata.  .']67.  442 
Poisoning,  definition  of.  19 
Poisons,  animal.  22 


IS,  131. 
liloratc  poisoning, 
yanide  poisoning. 


lV)i,sons.  i)acttrial,  3.!,  39 

caustic,  22 

clas.sificalion  of,  22 

different  sources  of,  19 

excretion  of,  98 

neutralization  of,  9S 

protection  against,  9S 

vegetable,  22 

volatile,  23 
Poison-theory  of  iinminiilv.  I  12 
Polar  field.  280 

corpuscles,  90,  278 
Poliosis,  2.57 
Pollen-diseases,  46 
Polyblasts.  299,  352 
Polydactylism,  532 
Polymastia,  534 
Polymelos,  545 
Polymitus,  710 

Polymorphism  of  cancer-cells,  45i 
Polymorphous  bacteria.  5.")().  .588 
Polypi,  hairy,  495 

valvular.  145 
Polythelia.  .")34 
Polyuria.  .')3.  79.  80 
Porokerato.sis.  213 
Post-mortem  hypost 
Potassium 
Potassium 

Precipitin-reaction.  121 
Precipitins.  109.  120 
Predisposition,  acquired,  44 

congenital,  44 

due  to  age.  47 

due  to  race,  48 

due  to  .sex,  48 

local,  45 

natural,  47 

special,  46 

temporary,  45 
Prepuce,  absence  of,  524 

hypertroj)hy  of,  524 

shortness  of,  524 
Pressure  atrophy,  188 

contimious,  effects  of,  16 
Proglottiles,  721 
Proliferation,  cau.ses  of,  277 

inflammatory,  350 

jjhenomena  ot,  323,  :!47 
Prosoposchisis,  517 
Prosopothoracoj)agus,  544 
Prostatic  calculi,  211 

concretions,  21 1 
Protective  mechanisms,  natui 
Proteins,  bacterial,  33,  39,  '>.'y 
Proteosoma,  712 
Proteus  vulgaris.  .")87 
Protliroriibiii.  137.  I  12 
Protophytr.  519 
Protoplasm.  2.S2 
Prototoxin.  610 
Protozoa,  parasitic.  42.  44.  t».s 
Psammomata.  437 
P.seudaliiis  capillaris.  639 

ovis  pulmonalis.  710 
Pseudodiphlheria  bacilli.  610 
P.seudohermaphro(lismus,  .'>35 


GENERAL    INDEX. 


Pseudomelaiiosis.  24.5 
Pseudomucin,  208 
Pseudotuberculosis,  638 

aspergillina,  638,  683 

cladotrichica,  638,  665 

due  to  animal  parasites,  638 

due  to  bacteria,  638 

due  to  foreign  bodies,  638 

due  to  lijijhomycetes,  638,  687 

vermian,  639 
Psorospermose  folliculaire  vegetante.  70.") 
Psychoneurosis,  17 
Ptbmains,  19,  38,  557 

toxic,  38,  557 
Puberty,  precocious,  266 
Pulegon,  poisoning  by,  23 
Pulex  irritans,  753 

penetrans,  or  sand  flea,  7.53 
Pulmonary  circulation,  increase  of  resist- 
ance in,  129 
Pulse,  acceleration  of,  127 

venous,  126 
Puriform  softening,  147 
Purpura,  1.59 

luemorrhagica,  160 

rheumatica,  160 

simplex,  160 
Pus,  339,  363 

inspissated,  calcification  of,  364 
Pus-cocci,  579 
Pus-corpuscles,  339 
Pustule,  340 
Putrefaction,  33,  38,  557 

alkaloids,  33,  38,  557 

zymoids,  38 
Putrescin,  33,  38,  557 
Putrid  gangrene,  178 
Pyemia,  37,  .572,  580 
Pj^elonephritis  of  cattle,  669 
Pygopagus,  541 
Pyknosis,  171 
Pyocyanin,  602 
Pyoseptha^mia,  .572 
Pyoseptictemia,  37,  572,  580 

Quinine,  poisoning  by,  29 

Rabies,  cause,  705 

protective  inoculations  against,  114 
Race,  predisposition  of,  48 
Rachicele,  509 
Rachipagus,  544 
Rachiscliisis,  partial,  508 

total,  508 
Radioactivity,  effects  of,  1 1 
Radium,  12 

Rag-sorters'  disease,  592 
Rainey's  bodies,  703 
Ray-figures,  281 
Ray-fungus,  659 
Rays,  Bccquerel,  11 

red  and  yellow,  sensitization  to.  11 

ultraviolet,  10 

violet,  10 
Receptaculum  scolicis,  724 
Receptors,  118 
Rectum,  cancer  of.  469 


Recurrent  fever,  92,  675,  693 

Redia^,  or  secondary  germ-sacs,  71(),  717 

Reduplications,  532,  .5.34 

Refrigeration,  9 

Regeneration,  272,  285 

causes,  273 

of  degenerated  tissue,  347 

partial,  274 
Regenerative  capacity  of  tissues.  276 
Relapsing  fever,  92,  675,  693 
Remittent  fever,  92 
Repair  by  first  and  by  secontl  intenti(jn. 

357 
Respiratory    apparatus,     aspergillus    mv- 

coses  of,  682 
Restitutio  ad  integrum,  274 
Retention  cyst,  258 
Retina,  glioma  of,  415 
Retrograde  changes,  167 
Reversion,  532 
Rhabditis  stercoralis,  742 
Rhabdomyoma,  411 
Rhabdomyosarcoma,  412 
Rhexis,  159 

Rhinoscleroma,  606,  657 
Rhizopoda,  689 
Ribs,  supernumerary,  55,  534 
Rice-water  intestinal  discharges  in  cliolera. 

671 
Ricin,  26 

immunity  to,  115 

poisoning  by,  26 
Rider's  bone,  397 
Rigor  mortis,  169 
Rinderpest,  immunization,  114 
Ringworm,  686 
Roseola  syphilitica,  643 
Round-cell  sarcoma,  421,  424 
Roundworms,  734 
Rudimentary  twin,  492,  545 
Russel's  bodies,  224 

Saccharomyces  ellipsoideus,  678 

litliogenes,  682 

neoformans,  682 
Saccharomycetes,  678,  682 

disease-producing,  678 
Sacs  of  Miescher,  703 
Sago-spleen,  214 
Salts,  caustic,  22 
Sand  flea,  or  pulex  penetrans,  753 

tumors,  437 
Santonin,  poisoning  by,  29 
Saprophytes,  35,  587 
Saprophytic  bacilli,  587 

cocci,  564 
Sarcina  lutea,  564 

ventriculi,  564 
Sarcinse,  549,  550,  564 
Sarcocarcinoma,  477 
Sarcocysts,  704 
Sarcoma,  419 

adeno-,  476 

angio-,  429 

alveolar,  425,  427 

cysto-,  492 

etiologv  of.  420 


CENKHAL    INDIA. 


Sarcoma,  fibro,  420.  4J8 

siant-ccU.  42:^ 

luriiiangii)-.  42.").  429 

larjie  rouiul-ct-UiHl,  422 

lyniphademudcs,  421 

lyinphangio-,  42o 

lyiupho-,  421 

medullary,  420 

melauo-,  433 

myo-,  424 

myxo-,  424 

organoid.  42.') 

ostco-.  416 

osteoid,  43() 

petrifying,  437 

phyllodes,  4,53 

plcxiformc,  427,  431 

polymorphous-celled,  418,  422,  423 

rhabtlomyo-,  412 

simple,  421 

small  round-celled,  421 

spindle-celletl.  423 

telangiectatic,  420 

tubular,  427 
S3*"comatosis  cutis,  424 
Sarcopliaga  magnifica,  754 
Sarcopliilia  wohlfarti,  754 
Sarcoplasm,  302 
Sarcopsylla  penetrans,  753 
Sarcoptes  hominis,  748 

minor,  751 

squamiferus,  751 
Sarcosporidia,  703 
Sausage-poisoning,  19,  35,  587,  000 
Scabies,  749 
Scald-head,  685 
Scall,  685 
Scarlet  fever,  705 
Scar-tissue,  274,  357,  363 
Schistoprosopia,  517 
Scliizogony,  701,  713 
Schizomycetes,  549 
Schizont.  704,  713 
Scirrhus,  473 

Sclera,  regeneration  of,  307 
Scleroma  respiratorium,  657 
Sclerosis,  222 

initial,  042 

of  nervc-tiss\ie,  304 
Scolex,  721 
Scrofula,  636 

Scrotum,  malformations  of.  .)24 
Scurvy,  160    - 
Scutula  of  favus,  685 
Sea-sickne.ss,  18 

Sebaceous  glands  in  dermoid  cysts.  490 
Secale  cornutum,  23 
Second  intention,  repair  Ijy.  352 
Secondary  infection,  38,  539,  ()35 
Secreticm,  internal.  79 
Segmentation,  direct,  280 

indirect,  280 
Segmented  skein,  281 
Semihmar   ganglia,    pathologicul    chaiiK 

m,  87 
Sepsin,  38,  557 
Sep.sis,  37 


.Sptua-mia,  37.  572.  .VS() 

iuemorrliagic.  ()(i.s 
Scpticojn'a'mia.  37.  572,  .VSd 
Se(iuestratioii  of  necrosed  tissue,  173  :;I7 

365 
Serpiginous  ulcers.  3(»S 
Serum,  healing,  1 12 

protective.  1 12 
Sex.  j)redispo.sition  of.  18 
Sexual  glands,  teratoid  tumors  of,  9il 

removal  of.  S.S 
Sexual  organs,   internal,   deveiopnu'iii    ..f, 

538 
Shock,  erethistic  and  tMipid.  |7 
Shottv  eruption.  795 
Side-('liaiiis,  1  IS 
Sid(>rofer()us  cells,  2^5 
Siderosis,  ha-matogeiinu^.  247 
Silver,  dejjosit  of,  23,  69.  219 
Simple  softening,  I  17 
Sirenomelia,  517 
Situs  inversus,  530 

Skein-like  structm-e  of  the  inicleus,  2S(1 
Skeleton,    pathological    clianges    in    tin-, 

50 
Skin.  al)sence  of  pigment  of.  257 

cancer  of.  460 

emphysema  of,  70 

liealiug  of  wovuids  of,  357 

l(>prous  nodule  of  the,  6.")0 

lupus  of  t  lie,  <i26 

melanotic  alveolar  sarcoma  of,  J:;.'! 

multi|)le  filiroinata  of  tlie.  .")3 

papillarv  epithelioma  of,  441 

pathological  alterations  of,  .52 

jngmeiitation  of,  87,  2;{S 
Skin-transplantation,  310 
Skull-cap,  angioma  cavernosmn  of,  492 
Sleejung  .sickness.  697 
Smallpox,  pustule,  339 

para.sites  of.  705.  707 
Smear  cultures,  561 
Smegma  bacillus,  621 
Snake  venom,  20,  2.3 

immunization.  1  15 
Soft  chancre,  61  I 
Special  sense,  organs  of,  new -format  ioi\  of 

the  tissues  of,  3t)7 
Specificity  of  tlie  tissues.  273 
Spermin.  89 
Spermolysin,  120 
Sphacelinic  acid,  23 
Sphacelus,  179 
Spluerobacteria.  549 
Spheres,  fatty  granule.  197 
Spider  cells,  304 
Spina  biKtla,  508 

anterior.  509 

cystica,  .309 

hnnbosacralis,  510 

occulta.  .-)(«) 

))osterior.  509 
.•-ipinal   column,   pressure  atrophy  of  the, 
iS9 

cord,  development  of.  51  I 
Spindle-celled  sarcoma.  12.5 
Spindle,  nuclear,  281.  2S2 


778 


GENERAL    INDEX. 


Spirilki,    or   .spirillacea",    or   spirobacteria, 

549,  670 
Spirillum  amyloferum,  553 

cholerse  asiatica?,  671 

deneke,  674 

of  Finkler  and  Prior,  674 

rubrum,  670 

rugula,  610 

serpens,  670 

sputigenum,  675 

tenue,  670 

tyrogenum,  675 

undula,  670 

volutans,  670 
Spirobacteria,  670 
Spirocha^te,  549,  670,  694 

buccalis,  670 

carteri,  694 

denticola,  670 

duttoni,  694 

gallinarum,  693 

kochi,  694 

novi,  694 

obermeieri,  693 

pallida,  641 

plicatilis,  670 

varieties  of,  670 

ziemanni,  694 
Spironema  pallidum,  641 
Spleen,  amyloid  degeneration  of,  214 

changes  in,  in  relapsing  fever,  693 

tissue,  reproduction  of.  295 
Splenomegaly,  infantile,  699 

tropical,  697 
Sporangia,  680, 
Spore-formation,  551,  586 
Spores,  34,  551,  703 
Sporoblasts,  701,  710,  713 
Sporocyst,  701,  704,  716 
Sporogenous  granules,  553 
Sporogony,  701,  704 
Sporozoa,  42,  701 

Sporozoites,  701,  704,  705.  710,  713 
Stab-cult  vuvs,  56 1 
Stadium  amphiboles,  92 

decrement i,  92 

incrementi,  91 
Staggers,  cause  of  the,  726 
Staphylococci,  549,  563,  578 
Staphylococcus  pyogenes  albus,  581 

pyogenes  aureus,  578 

pyogenes  citreus,  581 
Stars,  281 
Starvation,  5 
Stasis  of  the  blood,  150 
Stearin,  203 

Stegomyia  fasciata,  44,  699 
Sterilizod  cultures,  iniection  of,  112 
Stcrnopagus,  .'■)43 
Stigniatizatioii,  161 
Stoiuacli,  carcinoma  of,  474 
Stonio\yi<l;c,  7 .'■>:', 
Stomoxys  calcitrans,  697 
Stones  (concretions),  233 
Stone-cutter's  lung,  367 
Straddling  emboli,  68 
Strangles  of  horses,  585 


Streptococci,  550,  563,  565 
Streptococcus  articulorum,  573 

brevis,  573 

erysipelatis,  573 

lanceolatus,  575 

longus,  573 

meningitidis,  577 

mucosus,  573 

puerperahs,  573 

pyogenes,  565 

scarlatinosus,  573 
Streptothrix  madurse,  665 
Strongylides,  737 
Strongylus  armatus.  740 

bronchiahs,  740 

capillaris,  740 

commutatus,  740 

duodenahs,  737 

filaria,  740 

longevaginatus,  740 

micrurus,  740 

paradoxus,  740 

pusillus,  740 

rufescens,  740 

syngamus,  740 

tetracanthus,  740 

tracheahs,  740 
Strychnine,  poisoning  by,  29 
Substance,  fibrinogenic,  137 

lysogenic,  109 

zymoplastic,  138 
Sucking-mite,  751 
Sucking- worms,  716 
Suffocation,  4 
Suffusion,  158 
Suggillations,  158 
Sulphur-methsemoglobin,  26 
Sunstroke,  8 

Supernumerary  organs,  55,  532 
Suppuration,  causes  of,  341 
Suprarenal  cachexia,  87 

capsules,  altered  function  of.  87 
vSuprarenin,  87 
Surra,  697 
Susceptibility   to    infections    at    different 

ages,  47 
Sweat-glands  in  dermoid  cysts,  490 
Swine-erysipelas.  667 

immunization,  113 
Swine-plague,  668 
Swine-septicaemia,  668 
Sycosis  parasitaria,  676 
Symbiotes  equi  of  Gerlach.  751 
Symmetrical  gangrene,  179 
Symmyelia,  526 
Symptomatic  anthrax,  666 

protective  inoculations  against.  113 
Sympus,  526 
Syncephalus,  542 
Syncope,  17 
Syncytiolysin,  78 
Syncytiotoxin,  78 
Syncytium,  465 
Syndactylism,  528 
Syngamus  branchiaHs,  740 

trachealis,  740 
Synophthalmus.  515 


GENERAL     INDEX. 


S>aiotia,  olS 
Sypliilides,  643 

liereditary.  646 

transmission  to  foetus.  (I'J,  ()4S 
Syringomyelia,  50 
Syringomyelocele,  510 

Tab.\n"id.e.  753 

Tablet-formed  cocci.  54<t.  550,  563 

Tactile  irritability,  102 

Tsenia  africana,  726 

ccenurus,  726 

cucumerina,  726 

ecliinococcus,  727 

denticulata,  726 

diminuta,  726 

elliptica,  726 

expansa,  726 

flavapuncta,  726 

mamillana,  726 

niarginata,  726 

mediocanellata,  725 

minima,  726 

nana,  726 

perfoliata,  726 

plicata,  726 

saginata,  725 

serrata,  726 

solium,  722 
Tail,  formation  of  a,  in  the  luunan  being. 

.534 
Talipomanus,  530 

Tapeworms,  see  also  under  T(vnia.  721 
Tarichium  megaspermum.  6X7 
Tartar  of  the  teeth.  233 
Tattooing  of  the  .skin.  255 
Teeth  in  dermoid  cysts,  490 

supernvimerary,  534 
Telangiectasia,  398 

lymphatica,  404 
Temperature,  influence  of,  upon  develop- 
ment of  bacteria,  552 
Temperatures,  high,  of  the  body,  S 

low,  of  the  body,  9 
Tendinous  spot,  360 
Teratoid  cysts,  485,  495 

tumors,  485 
Teratoma,  autochthonous,  496 

bigerminal.  496,  545 

coccygeal,  495,  496,  545 

complex,  490,  495 

heterochronous  and  hetcrotofjous,  4S5 

monogerminal,  496 

of  sexual  glands,  490 

.sacral,  485 

solid,  492 
Terminal  artery,  163 
Testicle,  adenocystoma  of,  492 

adenomyosarcoma  of,  495 

angio.sarcoma  of,  430 

congenital  adenocy.stoma  of.  493 

dermoid  cy.sts  of,  49  1 

ectopia  of,  531 

retention  of,  in  the  al.ilniiiiiial  cavity, 
531 

teratomata  of.  492 


Tetanotoxin.  603 
Tetanus.  602 

antitoxin.  I  12,  1  15.  6().{ 
Tetanus-bacillus,  t)()2 
Tetany,  tiiyreoprival.  .SJ 
Tetracoccus,  56.3 
Texas  fever.  712 
Thallophytes,  677 

Thoracic  cavity,  faulty  cldsurf  of,  .'>2l 
Thoracic  duct,  rupture  of.  IOC) 
Thoracogast  ro,schisis.  520 
Thoracopagus.  543 

parasiticus,  547 
Thoracoschi.sis,  521 
Threadworms,  736 
Thrombin,  137.  142 
Thrombo-arteritis  purulenta.  1 4S 
Thrombogen.  13S 
Thronilx.kinasc.  13S 
Tlir()iiibo-})iilebitis  purulenta.   148 
Thrombo.sis,  1.36,  13S.  144 

sequela^  of,  146 
Thrombus,  144 

agglutination,  141 

autochthonous,  145 

formation  of,  139 

globular,  145 

induced.  145 

laminated,  139 

mixed,  139 

obturating,  145 

parietal,  145 

red,  138 

valvular,  145 

white,  139 
Thrush,  41,  679 
Thymus,  di.seasc  of,  89 
Thyreoprival  cachexia,  82 

tetany,  82 
Thyroid,  angiosarcoma  of.  430 

extirpation  of.  82 
Thyroiodine,  84 

Tibia,  tuberculous  di.seasc  c.f.  6:{0 
Ticks,  750 
Tinea  favosa,  685 
Tipulida>,  753 
Tissue-implantation,  l)igerniinal.  496 

monogerminal,  49(5 
Tissue-lesion,  320,  325 
Tissues,  restitution  of  tiie.  272 
Toes,  stunting  of,  52.S 
Tokelau.  6X7 

Toluyleiidiamin,  poi,soning  by,  26 
Tongue,  actinomyco.sis  of  the,  (MMJ 
Tongue- worms,  74X,  751 
Tophi,  gouty,  232 
Torula-ciiains.  563 
Toxalbumins.  IX.  33,  39 
Toxenzvnies,   10 
Toxic  .substances.  19.  36 
Toxina'uiia,  35 
Toxins.  33 

bacterial,  .51 

intracellular.  :{3 
Toxoids.  39,  9X 
Toxons,  39,  599 
Toxoses.  9X 


7S0 


GENERAL     INDEX. 


Transmissible  pathological  conditions  and 

tendencies,  55 
Transplantation,  809 
Transportation,  retrograde,  65 
Trauma,  effects  of,  16 
Traumatic  epithelial  cysts,  466 

neuroses,  17 
Trematoda,  42,  716 
Treponema  pallidiun,  641.  695 
Tricliina  spiralis,  743 
Trichocephalus  dispar,  743 
Tricholysin,  120 
Trichomonas  hominis,  689 

intestinalis,  44,  692 

vaginalis.  (592 
Trichomycetes,  550,  665 
Trichophyton  tonsurans,  685 
Trichophytosis,  687 
Trichothecium  roseum,  680 
Trichuris  trichuria,  743 
Tritotoxin,  610 
Trombidida?,  750 
Trophoblasts,  60 

Trophoneurotic  diseases  of  the  ti.ssues,  74 
Tropical  sore,  699 
Trj-panomonas,  695 
Trypanosoma  bruci,  44,  697 

equiperdum,  697 

equinum,  697 

evansi,  44,  697 

gambiense,  44,  699 

lewisi,  695 

noctuffi,  698 

theileri,  697 
Trypanosomiasis,  698 
Tsetse  disease,  677 
Tube-cocci,  549,  563 
Tubercle,  617 

solitary,  627 
Tubercles,  mihary,  625 
TubercuUn,  114,  622 
Tuberculomyces,  621 
Tuberculosis,  615 

avian,  637 

bacillus,  615 

bovine,  637 

hiBmatogenous  miliary,  633 

infection  with,  616 
Tumors,  371 

adenocarcinoma,  461 

adenocystoma,  448 

adenoma,  444 

adenosarcoma,  476 

angiosarcoma,  425 

benign  and  malignant,  383 

cachexia  accompanying,  384 

carcinoma,  455 

cavernous,  400 

chloromata,  435 

chondromata,  391 

chordoma,  393 

da.ssification  of,  374 

congenital,  52 

connective-tissue,  372 

cure  of,  383 

cyhndroma,  438 

cy.stic,  448 


Tunjors.  cystocarcinoma.  478 

definition  of,  371 

dermoid  cysts,  485 

desmoid,  385 

different  varieties,  372.  385 

enchondroma,  391 

endothelioma.  425 

epithehal.  373.  375.  44U 

etiology.  37(i 

fibroma.  3S5 

fihromyoina,  41 1 

fibro.sarconia.  423 

ghoma,  413 

growth  of,  379 

by  expansion,  380 
by  inhltration,  380 

hffmangiomata,  398 

histoid.  372 

hoinoplastic.  ;)74 

kcimd.  3S7 

leiomyonui.  409 

hpom'a,  389 

lymphangiomata,  398 

malignant.  384 

melanosarcomata,  433 

metastasis.  380,  384 

myofibroma.  411 

myoma,  409 

myxDchoudroma.  393 

myxofibroma.  387 

myx()li])onia,  387,  389 

myxoma,  3S7 

myxosarcoma,  387,  424 

neuroepitheHoma,  415 

neurofibroma,  417 

neuroglioma  ganglionare.  414 

neuroma,  416 

organoid,  420 

osteochondroma,  393,  396 

osteofibroma,  396 

osteoid  sarcoma,  436 

osteoma,  394 

papilloma,  385,440 

psammoma,  437 

recurrence  of,  383,  484 

retrogressive  changes  in,  382 

rhabdomyoma,  411 

sarcocarcinoma,  477 

.sarcoma,  419 

.secretion  in,  375 

structure  of,  372,  374 

teratoid,  374,  485  y 

Twin-formations,  rudimentary.  496 
Twins,  539 

homologous,  540 
Tympanic  cavity,  cholesteatomata  in.  442 
Typhoid-carriers,  596 
Tyj^hoid  fever,  bacillus  of,  594 

protective  inoculations  against.  ]  14 

of  fowls,  669 

of  mice,  668 
Typhus  recurrens,  693 

Udder-inflammatioxs,  7-)'>^7),  (i69 
I'lcer,  340 

chronic.  368 

indolent.  368 


GKXKHAl.     1\|)K\. 


Ulcer,  serpijiiiums.  'M\S 
Ulceration,  carcinoinatoiis. 

tul)on'ulous,  (V.M) 
T'lcus  atoiiicuiii,  l^dS 

callosuin,  ;>()S 

elovatuin  liy|H'rt  rophii 

iiulolcns.  ;i(")S 

mollc,  ()14 
Vmbilical  hernia.  ,VJO 
I'nciiiaria  anicricana.  7o7 

(luodenalis.  7^7 
Uraclius-cy.sts.  487 
I"ra:'inia.  7() 

I'rates.  tlo{)()sit  of,  in  ,sz:i)Ul, 
I'rethra,  abnormal  nari-owi 

absence  of,  524 

atresia  of,  524 
Urethriti.s,  gonorrhceal,  5iSJ 
Uric-acid  deposits,  231,  2:5.' 

infarct,  285 
Urinary  calculi,  235,  237 
Urobilin,  243 
T^robilinuria.  243 
Uterus,  adenocarcinoma  of. 

besimiing  carcinoma  o 

myoma  of,  409 
Uvula,  bifiu-cation  of.  517 


,  470 
f  c(>rv: 


:,  4(1 


Vaccixatio.v,  1 11 

Vaccines,  1 1 5 

Vaccinia,  705 

Vacuoles,  151.  171,  l'.)2.  327 

Valves,  lesions  of,  126 

Valvular  thrombus,  145 

Variation,  58 

Variola,  705 

Vascular  naevi,  399 

system,  pathological  change: 

walls,  pathologicil  alterations  of.  320 
Vasculitis,  proliferating,  301 
Vasomotor  nerves,  irritation  or  paralvsis 
^  of,  129 

Vein-stones,  234 
Venous  pulsation,  126 

pulse,  126 
Veratrine,  poisoning  by,  29 
Vermes,  716 
Verruca  carnea,  406 

senilis.  441 

vasculosa,  400 
Vertebra?,  supernumerary,  534 
Vertebral  canal,  deficient  closure  of.  50S 


in  tlic 


W'sicli'.s.  ;{•_".(.  332 
Nil)rio  cholera".  071 

of  MctsclmikolT.  675 

rugula.  670 

serpens.  670 
^'il)rion  butyriijue,  .").\,s 

.septi(iue  of  Pasteur.  604 
^■iscera.  al)normal  |>ositif>ns  of,  .■,:{() 

iluplications  of.  .")32 
Viscous  nietam()rplu)sis.  140 
Visual  apparatus,  patliologic.il  <uiuhtiiiii> 

of.  52 
Vitelline  duct,  cvst  of.  .->22 
Vitiligo.  257 
Volatile  poi.sons.  23 

WaNDEKING    CELt.S.  321 
Warts,  flesliy,  405 

iditlivo'tic.  261.   1 11 

senile,  441 

venereal.  269.  3()7 
Water,  effects  of  lack  of,  5,  6 
AVeights  of  differeni  organs.  206 
Weismann.  60 
Whip-worm,  743 
White  gangrene.  17S 
Whooi)ing-cough.  bacillus  of.  60 
Widal-Ciruber  reaction,  109.  .V.IC 
Wolffian  body,  496.  53S 
Wolffian  duct,  53.S 
Wolf's  .jaws,  517 
Wood-jack  or  wood-tick.  75t) 
Worm-disease  of  the  ox.  6(i9 
Worms,  42,  716 

l)arasitic.  42.  716 
Wound-dipiilheritls.  341 
Wound-granulations,  347 
Wound-infection.  45 
Wounds,  effects  of,  16 

healing     "".  356 

Xaxthint  calc  ri.i.  237 
Xiphopagus,  543 

Yeast-fungi,  677 
Yellow-fever,  614,  (599 

Zona  dekmatica,  509 

epithelo-serosa.  500 
Zooglcea,  550 
Zymase.  39 

Zymoid.  putrefactive.  3S 
Zvtiiopl:i<tic  substance,   i:!S.   I  12 


13  44  70 


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TTA01    An     irt"«r;                                        General  Library 

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